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%O =$V".Many patients have inadequate glycemic control//2       QRSTU&The evolution of management guidelines''" '  Studies including UKPDS have highlighted the importance of glycemic control in reducing complications New guidelines include tighter targets for glycemic control Guidelines recognize importance of treating all aspects of the condition Current guidelines therefore include targets for glycemic control lipid levels blood pressure^1 2>  y 2  3 2*3 ZD  P    3 \UKPDS: decreased risk of diabetes-related complications associated with a 1% decrease in A1C,]\ ] :UKPDS: the benefits of improved glycemic control;;$&*     Improved glycemic control significantly reduces risk of diabetes-related complications UKPDS results indicated that a 1% reduction in A1C would reduce the risk of microvascular complications by 37%, but have less effect (16%) on macrovascular complications Further improvement in sustained glycemic control and reduction in the burden of cardiovascular disease are needed70Z2&0Z 50Z20Z 40Z2I0Z t      C   2  R CUKPDS demonstrated loss of glycemic control with all agents studiedDD$2         IProportion of patients with A1C < 7.0% on monotherapy at 3, 6 and 9 yearsJZJ &*    !The UKPDS demonstrated progressive decline of b-cell function over timeNH.$$$$G   *#1998 CDA Treatment Targets$  V6O1 `7+$Lifestyle Intervention$   The first step in treating type 2 diabetes Nutrition therapy and exercise can improve glycemic control Success of lifestyle intervention related to: patient s initial fasting plasma glucose level amount of weight loss achieved by patient Only a minority of patients are able to attain treatment targets using lifestyle intervention alone. T-ZZ>sZZ0sZ]Z sZ=sZ1sZZm0]p&[    d;EUKPDS 7: Response of FPG to Diet Therapy in Newly Diagnosed PatientsFF$E   N= 3044, newly diagnosed patients FPG at diagnosis 12.1+/- 3.7 mmol/L Diet counseling Patients with FPG 10-12 mmol/L needed reduction of 28% ideal body weight; to attain FPG <6 mmol/L 16% achieved FPG <6 after 3 months: in the group presenting with FPGs of 6-8 mmol/L 50% met this target in the group presenting with FPGs of 16-22 mmol/L only 10% were successfulsZ/0 sZ &sZ6ZZ0 sZ 4ZZ0 sZ &D  /  D  G    9       %  &9Primary Sites of Action of Oral Antihyperglycemic Agents::$&!   |DKey Recommendations   VAntihyperglycemic agents should be initiated if glycemic targets not met after 2-3 months of lifestyle intervention Antihyperglycemic agents should be started concomitantly with lifestyle if A1C levels are greater than 9% The lag period before adding other agent(s) should be kept to a minimum to achieve glycemic targets within 6-12 months Unless contraindicated, metformin should be used first line; other agents should be considered in the order they appear in the treatment algorithm Insulin therapy should be initiated if targets cannot be achieved with lifestyle changes and oral therapy 0Vl ZZW   =    5    ,%*New Treatment Options for Type 2 Diabetes++$*   i>/Management of Hyperglycemia in Type 2 Diabetes00$&     DZ   M.N/ rB A1C <7% (< 6% if can be achieved safely) Aim to achieve targets within 6-12 months Start with combination therapy or insulin for patients with A1C > 9% Consider insulin at any stage of treatment Vascular protection to further reduce cardiovascular risk)l *l El +l :l k  ed  GHIJKLMNOc  WXYZ[\]^_`ab/<./23456 7 : ;?@A]a"f$k&s*t+u,v-w.x/y0~23589:;<=>?@ABCDEFGHIJKLMNOPQRSTU` ` ` ̙33` 333MMM` ff3333f` f` f` 3>?" dd@,|?" dd@   " @ ` n?" dd@   @@``PR    @ ` ` p>> 0(  B  s *޽h ? ̙33 Default Design 0 zr@d (  d d 0N P   N P*   d 0dN    N R*  d d c $ ?  N d 0N  @ N RClick to edit Master text styles Second level Third level Fourth level Fifth level!     S d 6!N `P  N P*   d 6T#N `  N R*  H d 0޽h ? ̙3380___PPT10.5 0$8(  $ $ 0}k  P   k  >*  $ 0k     k  @*  $ 6k  `P  k  >*  $ 60k  `  k  @* H $ 0޽h ? ̙3380___PPT10.: P$( w ` $ s *f"`\  ZEԔԔ8c8c?n xCanadian Diabetes Association 2003 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada>@9XZx   0lE`Z t This material has been reviewed by the Canadian Diabetes Association for its medical and scientific accuracy. Presence of the Canadian Diabetes Association Partners in Progress mark does not constitute an endorsement of the products or services of GlaxoSmithKline Inc.*    h " C @A(Box For Intros copyp   ZEԔԔ8c8c?L  m#Getting to Goal in Type 2 Diabetes.$#6,` # C 8A  Partners logo ap `0H  0޽h ? ̙33y___PPT10Y+D=' = @B + ) K0 ((`45'(  l 5 6f?"`~   f_N 1?e 1 Harris S, et al, The Diabetes in Canada Evaluation (DICE) Study, ADA 2003, 2162-PO 2 Harris MI, et al. Diabetes Care 1999; 22:403 408.0 72 S          333MMff  S ~,E?v2 @jJ?je  J"      ftoN]] 1?w[ @ g  Percentage of subjects$( 2  333MMff  <LxNT D  k0:48 Z2    <p% D m  l20:48 Z2    <~N| D   l40:48 Z2    <tN  D  l60:48 Z2    <xN D ; l80:48 Z2    <NBT D  m100:48 Z2    0ĐN$ `   i<7%6     0N $  j> 7%6     H4N ?" 1 WA1C (%)       ZN1?P p US (1988-1994)2B      NN ԔԔ8c8c?`k:  N   ZN1?L  a38%"      fN? 1?}j U62%"     C xN?v2 @jJ? E  L$( 2  4  #     S ~tN?v2 @jJ? D  J"      f N]] 1?TG  Percentage of subjects$( 2  333MMff  C x8N?v2 @jJ?   L$( 2    <ؾND )y  k0:48 Z2    <HN ye  l20:48 Z2    <Nu y  l40:48 Z2    <(Ny l60:48 Z2    <Ny8 l80:48 Z2    <NJy m100:48 Z2  4  #     0xN   j< 7%6     0N |  n 7%6     HN ?W WA1C (%)     ! ZN1?  @ } CAN (2003)1B       "  fN? 1?! U50%"    #  fN? 1?S U50%"   RB $ s *Do XB % 0Do  |B & TDo?{ |B ' TDo? v |B ( TDo? v |B ) TDo?v |B * TDo?[v \|B + TDo? v RB , s *Do XB - 0Do  |B . TDo?|B / TDo?  |B 0 TDo?  |B 1 TDo?|B 2 TDo?XY|B 3 TDo?  H  0޽h ? fr̙33y___PPT10Y+D=' = @B +.= }p&) (  f ) 0f"   6  }  Years T2DM.     hh88  3 r gֳgֳ ԔԔ8c8c?Vm 0,$ 0 QProportion of patients with A1C > 7.0 increases with duration of type 2 diabetesBRZ 1 R   6djJ m $ 0PH___PPT2001$XB  0DoXB  0DEoHXB  0DoXB   0DhXB   0DXh[XB   0D o XB   0D o XB   0Dn or XB  0D o XB  0D o XB  0D} o XB  0D2 o6 }  H" ? $ 0PH___PPT2001$ y<=2   hh88  H@F ?Y$ 0PH___PPT2001$ 3-50   hh88  HY ? V $ 0PH___PPT2001$ 6-90   hh88  H^ ? $ 0PH___PPT2001$ 10-140   hh88  Hq ?$ 0PH___PPT2001$ 15+0   hh88}l S  #S ,$D  0l  <2jJ S   HЁ ?  z $ 0PH___PPT2001$ 31%0   hh88}l J{  $J{ ,$D  0l  <2jJ{   HT ?7J7$ 0PH___PPT2001$ 42%0   hh88}l    % ,$D  0l  <2jJ    H  ?  T$ 0PH___PPT2001$ 53%0   hh88l f   &f  ,$D  0  T2jJf    H ? w$ 0PH___PPT2001$ 67%0   hh88}l N  'N ,$D  0l  <2jJpN    H ?J$ 0PH___PPT2001$ 62%0   hh88 "  ft  1?e >Harris,S et al. CDA 2003; Type 2 Diabetes and Associated Complications in Primary Care in Canada: The Impact of Duration of Disease on Morbidity Load.B 2    $   333MMffH  0޽h ? ̙33___PPT10+Dq' = @B D,' = @BA?%,( < +O%,( < +Dc ' =%(%(D' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*#%(D' =-s6Bwipe(left)*<3<*#D' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*$%(D' =-s6Bwipe(left)*<3<*$D' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%%(D' =-s6Bwipe(left)*<3<*%D' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*&%(D' =-s6Bwipe(left)*<3<*&D' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*'%(D' =-s6Bwipe(left)*<3<*'+-> &E?(  f E 0f"   3 r gֳgֳ ԔԔ8c8c?Vm 0,$ 0 SProportion of patients with hypertension increases with duration of type 2 diabetesTZT T  ! 6|  }  Years T2DM.     hh88 " 0djJ m $ 0PH___PPT2001$RB # s *DoRB $ s *DEoHRB % s *DoRB & s *DhRB ' s *DXh[RB ( s *D o RB ) s *D o RB * s *Dn or RB + s *D o RB , s *D o RB - s *D} o RB . s *D2 o6 w 0 B ? $ 0PH___PPT2001$ y<=2   hh88 2 B ?Y$ 0PH___PPT2001$ 3-50   hh88 4 B0  ? V $ 0PH___PPT2001$ 6-90   hh88 6 B0 ? $ 0PH___PPT2001$ 10-140   hh88 8 B8% ?$ 0PH___PPT2001$ 15+0   hh88ql S  @S ,$D  0f / 6)))2jJS  9 B ) ?  j$ 0PH___PPT2001$ 53%0   hh88ql T{  AT{ ,$D  0f 1 6)))2jJ{  : B@8 ?7T7$ 0PH___PPT2001$ 57%0   hh88ql  v  Bv ,$D  0f 3 6)))2jJ "  ; BxB ? v $ 0PH___PPT2001$ 64%0   hh88l f   Cf  ,$D  0~ 5 N)))2jJf `  < B 6 ? P$ 0PH___PPT2001$ 71%0   hh88ql N  DN ,$D  0f 7 6)))2jJ>N  = B` ?*$ 0PH___PPT2001$ 72%0   hh88 ?  fn  1?e >Harris,S et al. CDA 2003; Type 2 Diabetes and Associated Complications in Primary Care in Canada: The Impact of Duration of Disease on Morbidity Load.B 2    $   333MMffH  0޽h ? ̙33___PPT10+6Dq' = @B D,' = @BA?%,( < +O%,( < +Dc ' =%(%(D' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*@%(D' =-s6Bwipe(left)*<3<*@D' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*A%(D' =-s6Bwipe(left)*<3<*AD' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*B%(D' =-s6Bwipe(left)*<3<*BD' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*C%(D' =-s6Bwipe(left)*<3<*CD' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*D%(D' =-s6Bwipe(left)*<3<*D+-? &EY(  f E 0f"   3 r gֳgֳ ԔԔ8c8c?Vm 0,$ 0 SProportion of patients with dyslipidemia increases with duration of type 2 diabetesTZT&   ,  ! 6  }  Years T2DM.     hh88 " 0djJ m $ 0PH___PPT2001$RB # s *DoRB $ s *DEoHRB % s *DoRB & s *DhRB ' s *DXh[RB ( s *D o RB ) s *D o RB * s *Dn or RB + s *D o RB , s *D o RB - s *D} o RB . s *D2 o6 w 0 B ? $ 0PH___PPT2001$ y<=2   hh88 2 B ?Y$ 0PH___PPT2001$ 3-50   hh88 4 B ? V $ 0PH___PPT2001$ 6-90   hh88 6 B ? $ 0PH___PPT2001$ 10-140   hh88 8 B ?$ 0PH___PPT2001$ 15+0   hh88ql S  @S ,$D  0f / 62jJGS  9 B ?  0$ 0PH___PPT2001$ 55%0   hh88ql L{  AL{ ,$D  0f 1 62jJ{  : B8 ?7L7$ 0PH___PPT2001$ 57%0   hh88ql    B ,$D  0f 3 62jJ   ; Bt ?  $ 0PH___PPT2001$ 58%0   hh88l f   Cf  ,$D  0~ 5 N2jJf   < B ? $ 0PH___PPT2001$ 59%0   hh88ql FN  DFN ,$D  0f 7 62jJN  = B( ?F$ 0PH___PPT2001$ 66%0   hh88 ?  f`  1?e >Harris,S et al. CDA 2003; Type 2 Diabetes and Associated Complications in Primary Care in Canada: The Impact of Duration of Disease on Morbidity Load.B 2    $   333MMffH  0޽h ? ̙33___PPT10+6Dq' = @B D,' = @BA?%,( < +O%,( < +Dc ' =%(%(D' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*@%(D' =-s6Bwipe(left)*<3<*@D' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*A%(D' =-s6Bwipe(left)*<3<*AD' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*B%(D' =-s6Bwipe(left)*<3<*BD' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*C%(D' =-s6Bwipe(left)*<3<*CD' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*D%(D' =-s6Bwipe(left)*<3<*D+-8 &FI(  f F 0f"   3 r gֳgֳ ԔԔ8c8c?PH8*,$ 0 ]Proportion of patients with cardiovascular disease increases with duration of type 2 diabetes^Z^ ^  " 6  }  Years T2DM.     hh88 # 0djJ m $ 0PH___PPT2001$RB $ s *DoRB % s *DEoHRB & s *DoRB ' s *DhRB ( s *DXh[RB ) s *D o RB * s *D o RB + s *Dn or RB , s *D o RB - s *D o RB . s *D} o RB / s *D2 o6 w 1 B5 ? $ 0PH___PPT2001$ y<=2   hh88 3 B8A ?Y$ 0PH___PPT2001$ 3-50   hh88 5 B8M ? V $ 0PH___PPT2001$ 6-90   hh88 7 B; ? $ 0PH___PPT2001$ 10-140   hh88 9 Bda ?$ 0PH___PPT2001$ 15+0   hh88ql  S  A S ,$D  0f 0 62jJ S  : Bxe ?   $ 0PH___PPT2001$ 15%0   hh88ql  {  B { ,$D  0f 2 62jJ {  ; Bz ?7 7 $ 0PH___PPT2001$ 21%0   hh88ql   C  ,$D  0f 4 62jJ  < BHr ? P $ 0PH___PPT2001$ 24%0   hh88l f    D f  ,$D  0~ 6 N2jJf   = BD ?   $ 0PH___PPT2001$ 29%0   hh88ql `N  E`N ,$D  0f 8 62jJ0N  > B ?`$ 0PH___PPT2001$ 48%0   hh88 @  f  1?e >Harris,S et al. CDA 2003; Type 2 Diabetes and Associated Complications in Primary Care in Canada: The Impact of Duration of Disease on Morbidity Load.B 2    $   333MMffH  0޽h ? ̙33___PPT10+ Dq' = @B D,' = @BA?%,( < +O%,( < +Dc ' =%(%(D' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*A%(D' =-s6Bwipe(left)*<3<*AD' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*B%(D' =-s6Bwipe(left)*<3<*BD' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*C%(D' =-s6Bwipe(left)*<3<*CD' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*D%(D' =-s6Bwipe(left)*<3<*DD' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*E%(D' =-s6Bwipe(left)*<3<*E+-9 &Gb(  f G 0f"  " 3 r gֳgֳ ԔԔ8c8c?PH8*,$ 0 \Proportion of patients with microvascular disease increases with duration of type 2 diabetes]Z]&   4  # 6`  }  Years T2DM.     hh88 $ 0djJ m $ 0PH___PPT2001$RB % s *DoRB & s *DEoHRB ' s *DoRB ( s *DhRB ) s *DXh[RB * s *D o RB + s *D o RB , s *Dn or RB - s *D o RB . s *D o RB / s *D} o RB 0 s *D2 o6 w 2 B ? $ 0PH___PPT2001$ y<=2   hh88 4 B8 ?Y$ 0PH___PPT2001$ 3-50   hh88 6 B ? V $ 0PH___PPT2001$ 6-90   hh88 8 B ? $ 0PH___PPT2001$ 10-140   hh88 : B, ?$ 0PH___PPT2001$ 15+0   hh88ql F S  BF S ,$D  0f 1 62jJ S  ; B( , ? F  $ 0PH___PPT2001$ 21%0   hh88ql {  C{ ,$D  0f 3 62jJs {  < B0, ?77` $ 0PH___PPT2001$ 32%0   hh88ql  P  DP ,$D  0f 5 62jJ   = B, ? P $ 0PH___PPT2001$ 42%0   hh88l f   Ef  ,$D  0~ 7 N2jJf   > B1, ? $ 0PH___PPT2001$ 44%0   hh88ql N  FN ,$D  0f 9 62jJpN  ? B>, ?J$ 0PH___PPT2001$ 62%0   hh88 A  fL9,  1?e >Harris,S et al. CDA 2003; Type 2 Diabetes and Associated Complications in Primary Care in Canada: The Impact of Duration of Disease on Morbidity Load.B 2    $   333MMffH  0޽h ? ̙33___PPT10+Dq' = @B D,' = @BA?%,( < +O%,( < +Dc ' =%(%(D' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*B%(D' =-s6Bwipe(left)*<3<*BD' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*C%(D' =-s6Bwipe(left)*<3<*CD' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*D%(D' =-s6Bwipe(left)*<3<*DD' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*E%(D' =-s6Bwipe(left)*<3<*ED' =%(D7' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*F%(D' =-s6Bwipe(left)*<3<*F+a K0 phl(  lf l 0f"  l NX,  ԔԔ8c8c?`m :  ,   l Ha,  ԔԔ8c8c?TX ,  &xxhdlB l s *3޽h ? fr̙33y___PPT10Y+D=' = @B +( K0  ''+J '(  f J 0f" >  c <, 1?TX h Adapted from Stratton IM, et al. UKPDS 35. BMJ 2000; 321:405 412.B  g G G G G G  G  $<     N,  8c8c?m y  ,  4  # 2_    <4,   NPercentage decrease in relative risk corresponding to a 1% decrease in HbA1C "O O O   Z, 1?   p**2     Z , 1?< p Any diabetes- related endpoint ! ! ! B  c 3djJȜ s9?J  !  `ԧ, jJ?   a21%"    " Z, 1?   p**2    # Z4, 1?X hDiabetes- related death    B $ c 3djJȜ1 sȜ?g  %  `@, jJ? B  a21%"    & ZԿ, 1? xD  p**2    ' Z, 1?  eAll cause mortality    B ( c 3djJd1XȜ? v  )  `X, jJ?0 `  a14%"    * Z, 1?0 +  o*2    + Z, 1? W VStroke    B , c 3djJȜ1 sȜ?d   -  `, jJ?@ 2  a12%"    . Z, 1?``,  p**2   8 / Z0, 1? <Peripheral vascular disease B   B 0 C x3djJȜ s? 1  `, jJ? "w  a43%"    2 Zp, 1? P  p**2    3 Z, 1?z  Myocardial infarctionB     B 4 c 3djJȜ1 sȜ? F v  5  `x, jJ? `  a14%"    6 ZH, 1?@ p**2    7 ZD0 1? > hMicro- vascular disease    B 8 C x3djJȜ s? C  9  `x0 jJ?0   a37%"    : ZX 0 1? p  p**2    ; Z, 1?zP dCataract extraction    B < c 3djJȜ1 sȜ?aq  =  `0 jJ?` &  a19%"    > Z 0 1?9  ~,Observational analysis from UKPDS study data"- - - @B ? C foxD8 PH  I XP @"  S ~, 1?H  l Lower extremity amputation or fatal peripheral vascular disease *P = 0.035; **P < 0.0001~Z  AG G G G G  Y  @ Z0 1?PH  @  H  0޽h ? fr̙33y___PPT10Y+D=' = @B + K0 .&(  f  0f"   c )0 1?g hStratton IM, et al. UKPDS 35. BMJ 2000; 321:405 412.d5 2       5   N(00  ԔԔ8c8c?m   0    HX60  8c8c?,d 0  &xxhdlH  0޽h ? fr̙33y___PPT10Y+D=' = @B +3 K0 22z{T2(  f { 0f"   6h0   [ *     60   [ *   FB  S oX {Y FB  S o { FB  S o { FB  S o{FB  S o{FB  S o0 X FB  S o0 X FB  S o0 X FB  S o0 X FB  S o0 # $ X FB  S o0 X FB  S o {|X FB  S o{| FB  S Ԕ o FB  S Ԕ o FB  S oX Y 4  # 3 v@ 4  # 3 :@ 4  # 3 @ 4  # 3 I@ 4  # 3 @ 4  # 3  Y @ 4  # 3 @ 4  # 3 - i @ 4  # 3 @ 4  # 3 < x @ 4  # 3 @ 4  # 3 L @ 4  # 3  @ 4 ! # 3 \ @ 4 " # 3  @ 4 # # 3 k@ 4 $ # 3 /@ 4 % # 3 {@ 4 & # 3 ?@ 4 ' # 3 @ 4 ( # 3 N@ 4 ) # 3 @ 4 * # 3 "^@ 4 + # 3 @ 4 , # 3 2n@ 4 - # 3 @ 4 . # 3 A}@  / 60  V  [0*    0 6\0 n V.  [6*    1 6`0 | V<  [7*    2 68 VQ [8*    3 6h8 V_ [9*    4 6 8  ^M [2*    5 68  @M [4*    6 6h8  p M [6*    7 6 8  R M [8*    8 68  ^M \10*    9 <8 @ x  ]A1C*    ; <p$8 )M ^ (%)*    < 6!8 O<b  rYears from randomization*    = NL.8 1? L ?  qUpper limit of of normal = 6.2%" ( 2   _ > <18 8c?%,  7Conventional Glyburide Chlorpropamide Metformin Insulin 8 8Z                  hh88pB ? H?Do?|B @ T Df8c?|B A T D38c?W W |B B T D8c?  |B C T D8c?  pB D@ H?Ԕ?upB E@ H?Ԕ?1 upB F@ H?Ԕ? 1 YpB G@ H?Ԕ?Y pB H@ H?Ԕ?b pB I@ H?Ԕ? b pB J@ H?Ԕ? H pB K@ H?Ԕ?H I pB L@ H?Ԕ?H NI pB M H?Ԕ? NH FB N@ S fԔhFB O@ S fԔ# hZFB P S fԔ # ZFB Q@ S fԔ FB R@ S fԔV FB S@ S fԔ  FB T@ S fԔ P FB U@ S fԔP D FB V S fԔ# D FB W@ S foV FB X@ S ԔhFB Y@ S Ԕ# hFB Z@ S Ԕ # FB [@ S Ԕ FB \@ S ԔV FB ]@ S Ԕ  FB ^@ S Ԕ  FB _@ S Ԕ D FB ` S Ԕ# D FB a@ S Ԕ\ FB b S ԔJhrFB c@ S ԔJ# hFB d@ S Ԕ # UFB e@ S ԔU FB f@ S ԔV FB g@ S ԔV FB h@ S Ԕ^FB i@ S Ԕ^ FB j@ S Ԕ D FB k@ S Ԕ D# FB l@ S 3ԔwhFB m@ S 3Ԕ# hFB n@ S 3Ԕ # FB o@ S 3Ԕ # FB p@ S 3Ԕ# V  FB q@ S 3Ԕ V P FB r@ S 3ԔP Q FB s@ S 3ԔP  FB t@ S 3Ԕ D3 FB u S 3Ԕ# D3  v 6K8  )@ [0*    w HO8  ԔԔ8c8c?m   8   x  f0R8  1? e "UK Prospective Diabetes Study Group. UKPDS 34. Lancet 1998; 352:854 865.HI 2/G G G  I q???aa y 3 r(U8 1?` w)Overweight patients Cohort, median values* * * v z N1?pH  0޽h ? fr̙33y___PPT10Y+D=' = @B +tT K0 S{SehS(  f h 0f" f  Zpj8 1? g$ 0PH___PPT2001$0 PlTurner RC, et al. UKPDS 49. JAMA 1999; 281:2005 2012.7           7 hh88q  6T8  $ 0PH___PPT2001$ 100.   hh88  68 8(M Years from randomization.   hh88  C 1 %h $ 0PH___PPT2001$  C 1 %h $ 0PH___PPT2001$  C 1%h$ 0PH___PPT2001$$  S $8 1 %h+$ 0PH___PPT2001$ J"8 P2    c $8 1!%0 $ 0PH___PPT2001$     C o % $ 0PH___PPT2001$o  68   $ 0PH___PPT2001$ }3.   hh88o  68  .$ 0PH___PPT2001$ }6.   hh88o  648  T$ 0PH___PPT2001$ }9.   hh88o  68  "$ 0PH___PPT2001$ }0.   hh88p  68  g8 $ 0PH___PPT2001$ ~20.   hh88p  68  g2 $ 0PH___PPT2001$ ~40.   hh88p  6 8 gR$ 0PH___PPT2001$ ~60.   hh88p  68 gh$ 0PH___PPT2001$ ~80.   hh88  C 1  $ 0PH___PPT2001$  C 1  $ 0PH___PPT2001$  C 1$ 0PH___PPT2001$  C 1!,$ 0PH___PPT2001$  C 1) $ 0PH___PPT2001$  C o e $ 0PH___PPT2001$o  69  A$ 0PH___PPT2001$ }3.   hh88o  6 9  $ 0PH___PPT2001$ }6.   hh88o  69  $ 0PH___PPT2001$ }9.   hh88  C 1 C  $ 0PH___PPT2001$  C 1 C  $ 0PH___PPT2001$  C 1 C )$ 0PH___PPT2001$  C 10 C ;$ 0PH___PPT2001$  C 1, C 7$ 0PH___PPT2001$ ! c $L"9 jJ. $ 0PH___PPT2001$    " C o   $ 0PH___PPT2001$o # 60/9   $ 0PH___PPT2001$ }3.   hh88o $ 60;9 O$ 0PH___PPT2001$ }6.   hh88o % 6HD9 P$ 0PH___PPT2001$ }9.   hh88 & C 1 i $ 0PH___PPT2001$ ' C 1 i $ 0PH___PPT2001$ ( C 1i)$ 0PH___PPT2001$ ) C 10i;$ 0PH___PPT2001$ * C 1.it $ 0PH___PPT2001$ + C o o $ 0PH___PPT2001$o , 6O9 F$ 0PH___PPT2001$ }3.   hh88o - 6b9 y$ 0PH___PPT2001$ }6.   hh88o . 6n9 $ 0PH___PPT2001$ }9.   hh88d / 6o9 /w$ 0PH___PPT2001$ rDiet    hh88g 0 6x9 0$ 0PH___PPT2001$ uInsulin    hh88w 1 6@9 ?&$ 0PH___PPT2001$  Metformin      hh88z 2 69 ?d k$ 0PH___PPT2001$  Sulfonylurea.     hh88B 3 HD1?, @, $ 0PH___PPT2001$ 4 TD9 wawa8c?+U$ 0PH___PPT2001$ Overweight patients6( 2  hh88 5 ZD9 wawa8c?O4 $ 0PH___PPT2001$ Proportion of patients (%)$( 2  hh88[ 6 Hx9 8c?$S $ 0PH___PPT2001$ W50%$ Z   7 C 1*5$ 0PH___PPT2001$ 8 C 1!%h,$ 0PH___PPT2001$ 9 3 r9 gֳgֳ ԔԔ8c8c?m <$ 0  9  d : <v2 @jJ a :B ; 3 jJe  :B < 3 jJl m d = <v2 @jJ  :B > 3 jJ  :B ? 3 jJ 0 d @ <v2 @jJ  :B A 3 jJ 12 :B B 3 jJ N  C  `?v2 @jJ? ( :B D 3 jJe  :B E 3 jJe {f  F  `?v2 @jJ? m I *F  I  G I fB H 6?jJ? I fB I 6?jJ? I J :B J 3 jJ: w :B K 3 jJ: ; d L <v2 @jJ x T :B M 3 jJF :B N 3 jJF  G d O <v2 @jJ1  :B P 3 jJ : :B Q 3 jJ = d R <v2 @jJ  :B S 3 jJ ^_ :B T 3 jJ F}  U  `?v2 @jJ?  :B V 3 jJo eg :B W 3 jJo Op  X  `?v2 @jJ? 7 ^B Y 6?jJ?S  ^B Z 6?jJ?S T  [  `?v2 @jJ? sH ^B \ 6?jJ?z  ^B ] 6?jJ?z {  ^  f9 1?%N eError bars = 95% CI"( 2   _ C 1.j9$ 0PH___PPT2001$v ` N1? 9*F  I  a  a fB b 6?jJ? I fB c 6?jJ? I J  e  f?v2 @jJ?K N# H  0޽h ? 'Qggg=3ey___PPT10Y+D=' = @B +U1 K0  P0H0LL/(  f L 0f"   N9  ԔԔ8c8c?m   9  @B  C o 2 @B  C o  @B  C o {| @B  C o b d @B  C o KL   6d9 D42 a100.    @B  C o  @B  C o  @B  C o  @B  C o  @B  C o ~   @B  C o q q  @B  C o j k  @B  C o XY @B  C o ]^ @B  C o GH @B  C o @A @B  C o 22 pB  HDԔ? f pB  HDԔ? f pB  HDԔ?sbspB  HDԔ?t  6\9 ( `80.      6 9 0^ `60.      6$9 Q 0  `40.    |B  TDԔ? pB  HDԔ? HpB  HDԔ?rHA pB  HDԔ?U pX pB  HDԔ? jHi pB ! HDԔ?e xP d " <?3?a0 d # <?3?A,d $ <?3?! $zw d % <?3?a v d & <?3? j d ' <?3?5 v d ( <?3?I b . ) 3 r9  jJ? Y   P < 0.00012        __4 * S ~9 1?QW  HOMA model, diet-treated n = 376! 2!$      + 69 )p kTime from diagnosis (years)      , 6; D47 S100      - <4; i` @  &b-cell function (%)4 0         pB . HDo? pB / HDԔ?L lL pB 0 HDԔ?fpB 1 HDԔ?xbx 2 6 ; ( R80      3 6 ; 0c R60      4 6H; V 0  R40      5 6;  ,  R20      6 6l;  47  Q0      7 3 r\#;  jJ? G^M X     __B 8 ZD>?] ]  9 Z$%; 1?  bStart of treatment     : c ); 1?  k PAdapted from Holman RR. Diabetes Res Clin Pract 1998; 40 (Suppl.):S21 S25.>K    Z!        ; Zx0; 1?/  b 10      < Z 5; 1?/  ` 9      = Z8; 1?/  ` 8      > Z<; 1?/  ` 7      ? Z@; 1?/  ` 6      @ ZD; 1?/  ` 5      A ZlH; 1?/   ` 4      B ZHL; 1?/  ` 3      C Z$P; 1?/  ` 2      D ZT; 1?/  ` 1      E ZW; 1?/  ]1      F Z[; 1?/  ]2      G Z_; 1?/  ]3      H Zpc; 1?/  ]4      I ZLg; 1?/  ]5      J Z(k; 1?/  ]6     v K N1?*LlH  0޽h ? ̙33y___PPT10Y+D=' = @B +K0    (  f  0f" Z  Zt; ԔԔ8c8c?U xCanadian Diabetes Association 2003 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada<@9XZx  h  C @A(Box For Intros copy@@@0 $  3 rtv; 1ԔԔ8c8c?0 p]  Glycemic Targets4 ,,   N  63f ;޽h ? fr̙33y___PPT10Y+D=' = @B +3 K0 220NNtb2(  tf Nt 0f"  t # l; 1? JI CMAJ 1998; 159 (8 Suppl):S1-294       t Nl;  ԔԔ8c8c?6  ;  p t c $A ? A  ;  t 6D; [ A MLevel,  t 6\; D AIdeal   t 6; *B  S(normal0  t 6;  X b nondiabetic)      t 6;   D TOptimal*0    t 6; *d I  Y (target goal)0    t 6;  D F Suboptimal     t 6; ! f @     t 6; *  G (action may    t 6|; X X be required)0    t 6 ; |D F Inadequate    t 6;  f ! @    t 6@; * S(action0  t 6; X E required)   : t 3   : t 3 ; ? t 6; J6  Glycated @   t 68; 46 XHb   t 6; /J  G (% of upper    t 6; J~] Blimit)   t 6d; VJ G e.g., HbA1c    t 6(; J Aassay   t 6; / K<.  t 6; / M100.  t S ;  D    t 6; W< ] S (.04-.06).    t 6|; /D  K<.   t 6; / d  M115. : !t 3 D  "t 6`;  ] Q(<0.07).  #t 6; /wL Q116-140.  $t 6D< pU] S (.07-8.4).    %t 6< /]} N>140.  &t 6 < ] R(>0.084).  : 't 3 $( (t 6<  J  T Fasting or.    )t 6<  J<<  spremeal glucose.   *t 6< 5 J  Qlevel (.  +t 6|< 5   kmmol/L).  ,t 6<   <  Q3.8-6.1.  -t 6#<  x 1 <  M4-7.  .t 6(<  <  P7.1-10.  /t 6.<  Y<  M>10.  0t 61< [ J  W Glucose level.   1t 646<  J  Z1-2 h after meal.  2t 6:<  Ju  K(.  3t 6><  tg  kmmol/L).  4t 6B<    O4.4-7.  5t 6\G<   P5.0-11.  6t 6xE<  ;  Q11.1-14.  7t 6I<  Y  M>14. : 8t 3   : 9t 3  4B :t #   4B ;t #   : t #   4B ?t #  : @t 3   : At 3  4B Bt #  4B Ct #  : Dt 3  $ : Et 3 $( 4B Ft #  $( 4B Gt #  $% : Ht 3  (  It NX< 1?1  l :  2   Jt N^< 1?H ":Hb = hemoglobin *These levels are likely related to minimal long-term complications but may be impossible to achieve in most paients with type 1 diabetes with current therapies Attainable in the majority of people with diabetes but may not be adequate to prevent compications ! These levels are related to a markedly increased risk of long-term complications, requiring a reassessment and readjustment of therapy v0 F2 2  c   N {      pB Kt HD1?``pB Lt HD1?RpB Mt HD1?  H t 0޽h ? fr̙33y___PPT10Y+D=' = @B +'( }u@ (  f  0f" R  s *fBLB  c $DBLB  c $D  BLB  c $D BR  s *fB0 LB  c $DB0 LB   c $DB  2 LB   c $DB    <t< "  X A1C** (%)2  1   0v< " ,$D 0 FPG/preprandial PG (mmol/L)2, #   0< ";,$D 0 2-hour postprandial PG (mmol/L)2   0@< 0P RTarget for most patients  0<  ,$D 0 V7.02  0`< K ,$D 0 A4.0-7.0  0< [,$D 0 V5.0-10.02 nL   # 0  Z  s *f TB  c $D TB  c $D   LB  c $D   0ԕ<  ;  JNormal range (considered for patients in whom it can be achieved safely) K K  0<   ,$D 0 V6.02  0<  K  ,$D 0 U4.0-6.02  0<  + ,$D 0 U5.0-8.02c  0Ч<  {{  A1C = glycosylated hemoglobin DCCT = Diabetes Control and Complications Trial FPG = fasting plasma glucose PG = plasma glucose4 G ,  b  Tܭ<  ԔԔ8c8c? 12003 CDA Recommended Targets for Glycemic Control22$&!    H  0޽h ? ̙33RJ___PPT10*+6bF0DN' = @B D ' = @BA?%,( < +O%,( < +DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<* %(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<* %(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(DA' =%(D' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(++0+ <  ++0+ <  ++0+<  ++0+<  ++0+<  ++0+<  ++0+<  ++0+<  +  5 P t(  tf  t 0f"  t T<  ԔԔ8c8c?`j Components of Glycemic Control$&    { t Np< ԔԔ8c8c?@ ` 92 h. Postprandial Plasma Glucose 5-10 mmol/L 5-8 mmol/L*`!8P282 @'      t NT< ԔԔ8c8c?@ u =;Fasting/Preprandial Plasma Glucose 4-7 mmol/L 4-6 mmol/L* (282 8202#$Z        T t N(< ԔԔ8c8c?0` # A1C <7%, <6%* (2 $    t 0< 0` h*If can be achieved safely 2  d8     t  R  t Zspppp?  R t Zppppp?  H t 0޽h ? ̙33y___PPT10Y+D=' = @B +-"K0 <4p(  f  0f" h  C @A(Box For Intros copyb Z  ZL< ԔԔ8c8c?U xCanadian Diabetes Association 2003 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada<@9XZx  N  3 rD 1ԔԔ8c8c?0   .Management of Hyperglycemia in Type 2 Diabetes4/ .,,&    N  63f ;޽h ? fr̙33y___PPT10Y+D=' = @B +W  ~v(  f  0f"   N  ԔԔ8c8c?fm @     N  ԔԔ8c8c?    (y*xhdlH  0޽h ? =_933y___PPT10Y+D=' = @B ++ $ RJ( @B@ f  0f"   Nlǻ ԔԔ8c8c?m      N'  ԔԔ8c8c?    (y*xhdl  0) ` l Metabolism, 1990; 39(3): 905-912! 2!  ! H  0޽h ? =_933y___PPT10Y+D=' = @B +  K0 B(  f  0f" h  C @A(Box For Intros copy ` ,  3 r 6 1ԔԔ8c8c?_- Antihyperglycemic Agents4 ,,  N  63f ;޽h ? fr̙33y___PPT10Y+D=' = @B +T K0  :Q(  f Q 0f"   HE ?, H 8 P2   X  0A|h  v  NA1??  B?CDE(F2? ?7.$ @` (   BTC DE(F2? TI< 0 %   @` 2 *  BaCDELFV?J    a][YVT P N J(,@` 9 *  BgCDELFV?W   geca_] [ Y W(,@` > j  BBlC DElFv?a lkiige c a a 8<@` B j  BBnCDElFv?g nnnlkk i i g8<@` D    BHCDEF?%%B   HHFFDD D B ByfTC2!MP@`@` G    BpC DEF?%%j     ppnnnn l l j  k T = (MP@`@` I     BC DEF?..        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OP@`@` T   #  B7CDEF!?&&7  7777777 7 7      OP@`@` T   $  B0C DEF!?&&0     000000 0 0 0       OP@`@` T   %  B(C DEF$?&&(    ((((((( ( (      OP@`@` T   &  B#CDEF$?&&"   #""""" " " "        OP@`@` U  '  BCDEF$?&&             OP@`@` U  (  BC DEF&?&&             OP@`@` V  )  BCDEF&?&&             OP@`@` V  *  B CDEF)?&&                    OP@`@`  V  +  BC DEF)?&&             OP@`@`  V  ,  BCDEF)?&&          OP@`@` V  -  BCDEF+?&&        OP@`@`  V  .  BC DEF+?&&            OP@`@`  V  /  BCDEF. ?&&zzz z zzzzz      OP@`@`  V  0  BCDEF.?&&vv v vvvvvv       OP@`@`  W  1  BC DEF.?&& p p p p ppppp    ~   ~ OP@`@` W   2  BCDEF0 ?..lll l lllll  ~     ~_`@`@` # W   3  BCDEF0?..ii i iiiiii  ~        ~_`@`@` % W  4  BC DEF3 ?&& c c c c ccccc    ~   ~ ~ OP@`@` * X  5  BC DEF3 ?&& _ _ _ ______   ~  ~ ~ OP@`@` - X  6  BCDEF3?&&]] ] ]]]]]]      OP@`@` . X  7  BCDEF6 ?&&YY Y Y YYYYY       OP@`@` 2 X  8  BC DEF6 ?&& V V V VVVVVV      OP@`@` 4 Y  9  BCDEF6?&&RR R R RRRRR       OP@`@` 8 Y  :  BCDEF8 ?&&NN N N NNNNN       OP@`@` : Y  ;  BC DEF8 ?&& J J J JJJJJJ     OP@`@` > Y  <  BCDEF; ?&&HH H H HHHHH      OP@`@`} @ Y   =  BC DEF; ?.. D D D DDDDDD      _`@`@`y B Y   >  BC DEF; ?.. A A A AAAAAA      _`@`@`r E Y }  ?  BCDEF= ?&&=== = =====     OP@`@`l H Y y  @  BC DEF= ?&& 9 9 9 999999     OP@`@`h L Y r  A  BC DEF@ ?&& 5 5 5 5 55533       OP@`@`b N Y l  B  BCDEF@ ?&&111 / /////     OP@`@`] R Y i  C  BC DEF@ ?&& + + + ++++++     OP@`@`Y T X c  D  BC DEFB ?&& ( ( ( ( (((((       OP@`@`R W X ]  E  BCDEFB ?&&$$$ $ $$$$$     OP@`@`L Z X Y  F  BC DEFE ?&&              OP@`@`H ] X R  G  BC DEFE ?&&             OP@`@`B a Y L  H  BCDEFE ?&&        OP@`@`= d Y H  I  BC DEFG ?&&            OP@`@`8 f Y B  J  BCDEFG ?&&                 OP@`@`2 k Y =  K  BCDEFJ?&&               OP@`@`- n Y 8  L  B{C DEFJ ?&&{     zzzzzz z { {     OP@`@`( r Y 2  M  BvCDEFJ ?&&v   vvvvvv v v v      OP@`@`! v X -  N  BqCDEFL?&&q  qqqqqqq q q     OP@`@` y X (  O  BkC DEFL ?&&k     iiikkk k k k      OP@`@` ~ Y !  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OP@`@` T  J V  "B3C DEFT?663     /111133 3 3         op@`@` R J W  "B(CDEFT?66(     $&&&&( ( ((        op@`@` R  X  BC DEFW?&&            OP@`@` Q  Y  BC DEFW?&&            OP@`@` O  Z  BCDEFW?&&         OP@`@` M   [  BC DEFY?.. ~ ~ | ||zzzx        _`@`@` K   \  BC DEFY?.. r p p p nnnmm          _`@`@` K  ]  BCDEF\ ?&&fff e eeccc       OP@`@` J  ^  BC DEF\?&& \ \ Z ZZXXXV         OP@`@` H  _  BC DEF\?&& R P P P NNNLL           OP@`@` E  `  BCDEF^ ?&&GGG E ECCCA       OP@`@` D  a  BC DEF^?&& = ; ; ;99977         OP@`@` C  b  BC DEFa ?&& 1 1 1 / /---+          OP@`@` ?  c  BCDEFa ?&&*( ( (&&&$$        OP@`@` >  d  BC DEFa?&&         ~        ~ OP@`@` =  e  BCDEFc ?&&      |       ~ ~ |OP@`@`  :  f  BCDEFc?&&         z    ~~| | zOP@`@`  8  g  BC DEFf ?&&     ~~    y      ~~|| z z y OP@`@` 7  h  B|CDEFf ?&&| tvvxxx z z |v    ~||zzz x x vOP@`@`  5  i  BtCDEFf?&&t nnppprr t tv    ~||zzxx v vOP@`@`  2  j  BjC DEFi ?&&j effhhh j j j t   |zzxxv v t t OP@`@`  /  k  BeC DEFi ?&&e ```bbcc e e u    {{yyyww u u OP@`@`  -  l  B^CDEFi?&&^ XXZZ\\\ ^ ^u    zzxxwwu u uOP@`@`{  +  m  BVCDEFk ?&&V NPPRRR T T Vq   xvvvtt r r qOP@`@`v # )  n  BNC DEFk ?&&N HHJJJLL N N p  xvvttrr r p OP@`@`q & & {  o  BFCDEFn ?&&F @@BBDD F F Fp   vvvttr r p pOP@`@`k * $ v  p  BCCDEFn ?&&C ;==??? A A Cs   yywwuu u s sOP@`@`e + " q  q  B;C DEFn ?&&; 6677799 ; ; q   yywwuus s q OP@`@`a .  k  r  B3CDEFp ?&&3 ..0022 3 33q  xvvuuu s sqOP@`@`Z 1  e  s  B.C DEFp ?&&. &((***, , . q  vvvttrr q q OP@`@`W 4  a \ t  4BC DEFs ?88( """$$&& ( ( r   xxvvttt r r 9ytld]UQNJHD@<9tx@`@`@`U 6 _ \ u  4BCDEFs ?88     p  xvvvtt r rp t h ] Q H @ 6-%tx@`@`@`O 9 [ d v  <BC DEFs ?99 2 (           q ywwuuss s q vx@`@`@`L ; V d w  <BC DEFu ?99              s   yywwwuu s s vx@`@`@`E > P d x  <BCDEFu ?99             u  zyyyww u uuvx@`@`@`? ? L d y  <BC DEFx ?99           s  zxxvvvu u s vx@`@`@`; B E d z  <BC DEFx ?99     xrke         t    zzzxxvv t t vx@`@`@`5 D !? R {  *BCDEFx ?77zt n ga[UNH  ~ ~||zzzzzzxxvvt t  qt@`@`0 F !; R |  *BC DEFz ?77 _ Y S LF@;5/   z z z x x xxxxxxvv v v v t  qt@`@`+ H !5  }  BCDEFz ?&&D> 9 3 -'"       OP@`@`% J !0   ~  BCDEF} ?..+%        _`@`@` K + J   "BC DEF} ?66     |~       op@`@` L % J   "BCDEF} ?66   PX_gmtz           op@`@` P      BvCDEF ?..v  ,7AJV] g n v  _`@`@` R     BLCDEF ?&&L    $-5 = DL   OP@`@` S     B(CDEF ?&&(       (   OP@`@` T     BC DEF ?&&         OP@`@` V     BCDEF ?&&  |xt     OP@`@` X      BC DEF ?..  ~ | x trnliiigggeee    _`@`@` Y |     BC DEF ?.. p p n l l j h h g eca_[YWU{      _`@`@` [ i    BCDEF ?&&a][ W SQNJHbhnt{     OP@`@` ] U    BxC DEF ?&&x R P M IGCA=;KPV\agm s x  OP@`@` ^ B    B_C DEF ?&&_ E A ? ; 9842.47=CIN T Z _  OP@`@` _ 0    BGCDEF ?&&G762 0 ,*($" &,25 ; AG  OP@`@` a     B2C DEF ?&&2 , * ( $"!  & , 2    OP@`@` a     BC DEF ?&&              OP@`@` b    BCDEF ?&&        OP@`@` d    BC DEF ?&&        OP@`@` f     BCDEF ?..         _`@`@` f     BCDEF ?..           _`@`@` h    BC DEF ?&&      OP@`@` i    BCDEF ?&&      OP@`@` j    BCDEF ?&&      OP@`@` j    BC DEF?&& tvx|}     OP@`@` l    B}C DEF ?&&} hlnptvx | }    OP@`@` m    BrCDEF ?&&r _acehj l n r  OP@`@` o    BeCDEF?&&e TVXZ^` b d e  OP@`@` o    B^C DEF ?&&^ KOPRTVX Z ^  OP@`@` o |    BRCDEF?&&R ACEGIM N P R  OP@`@` q t    BICDEF?&&I 9;=?AC E G I   OP@`@`~ q m    B?C DEF ?&&? 024679; = ? ~~ OP@`@`z r g    B7CDEF?&&7 ~(*,.02 4 67  ~~~~~~ OP@`@`t r ` ~   B.C DEF ?$$. ~~||zzzz|||| | |  "$&(* , . 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( 7*@0I6P9S:]<h?sB}EHJLOQSUWXZ\] ^^#`/`:aFaQb]cicuccddZ@      K 6    B>CWDEF(1??DD;B2C)EFGGHIJJKKKKJIGFFEDC?=|<u9o6i5b1[/V*O& I1P5W8]=b?jBqDxHJKMPQRRSUVWWWWVVUTTS!R*Q3O<N>N;B@ F c P    ^B CDE F(1??CC&-6=EMSZbipv|wnf\SI?5+  %0;EPZdnw|voh`YQJB;2+# @ c  I    ^BCDEF$(1??GG%+3};wCpJjQbY\`WhPpKwE~A;71-(#  "',/59=CGMRW|\ubmjeo^vV{OHA91+$@     ^BCDEF(1??DD (1;ENW`irz}tlbYOE:/$ ! -8DOYcmv~vmcZQG>4*  @% U     ^BXCbDEF(1??DD,15(8<<N?bAuDFGHHIIHH!G6EGD[An>;74/*% (:M^ aO<"+(.48>AFILOoQ\SHT6U"WWWWUTSQOuL`JMF:B'?;9,@ZN +    BCDE F(1??CC -41;6A:E?KCQFWJ[NaRgVjZq^va|fhlpsuy|~|yvr}owkqgkaf^`ZZVVSPNJJDE@A:=54+@ | cdB  <o??  ZT 1?? K  UInsulin f  2  # E$GHQ I`TQ8c?? `TT`TT`T`T`TT`T`T  2  C ZB fENGJ&HIQ8c?? d$g fFd$g fF`T fF`T    ` xaxa1?? J  QI       f@ 1??h   QI      # l 1?? H p  QI      # l" 1??   QI      # lX 1?? 4 2  QI       f 1??  B :  QI      # l? 1??   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Diabetes Obes Metab 1999; 1 (Suppl. 1):S32 S40. Nattrass M & Bailey CJ. Baillieres Best Pract Res Clin Endocrinol Metab 1999; 13:309 329.b   4 /  #                        H  0޽h ?/    fr̙33: 2 ___PPT10 + bD ' = @B D ' = @BA?%,( < +O%,( < +D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*M%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*P%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*N%(D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*O%(+c 2 $( nw $f $ 0f"  $ T5  ԔԔ8c8c?"`     $ T6  8c8c?"`    H $ 0޽h ? ̙33y___PPT10Y+D=' = @B +( K0 $$01AP%$(  f A 0f"   C xH d @8c?J  `Diet/ exercise"   $  C xpB d @8c?5 J  |Oral monotherapy" &       C xO d @8c?6 J  cOral combination"     C xS d @8c?XJ  YInsulin"   vB @ N1?  v  Nd1?  v   Nd1? y vB   N1? zz vB   N1? , vB   N1? %%     B=C=DEFd@1?9<<9< @  F F  <   = B   BCgDE4F<̙@? A SAalfaXA%@F  < 2  # lxZ gֳgֳ̙2?F    B    xB B H1?U  F  v   H  R   "BCgDE<FD̙@?. =RCakfaWC3$  @  v 2  # l] gֳgֳ̙2? J  B    xB B H1?  :l R  @R  ,$D 0" B # lZG_nOH,I/Ԕ?R  S    `(b 1?  0Early aggressive combination therapy as required"1 1 1 |B  TDԔ?    Zf 1?{v b dStepwise treatment"      C x$k d @8c? J  cOral +/- insulin"   vB  @ N1? D v ! Nd1? ^F v " Nd1? b vB # N1?  vB $ N1?  vB % N1?   &  B=C=DEFd@1?9<<9< @ #` F F  <  '  j B (  BCgDE4F<̙@? A SAalfaXA%@F  < 2 ) # ltr gֳgֳ̙2?F    B    xB *B H1?U   , c BCjDE0F8? H`x 7Ix[`dHiiH@5 u  - c BCjDE0F8? Ei)d[I7 )EiEi@5 v 0 .  BC)DE,F41? #$5(G(|((((@c   / N|u  ԔԔ8c8c?m      6 <(x  z     7 c BCjDE0F8? H`x 7Ix[`dHiiH@P `  8 c BCjDE0F8? Ei)d[I7 )EiEi@P @ B ; ZZDԔ?B < ZZDԔ?B = ZZDԔ?  ^B ? 6DԔ  H  0޽h ?  fr̙33~___PPT10^+կG|DB' = @B D' = @BA?%,( < +O%,( < +D4' =%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*@%(+2 & P0p(  f 0 0f"   NL  ԔԔ8c8c?     s *      (y*xhdl ` +# `,$D  0f  6`  B؎ `@ }EClinical assessment and initiation of nutrition and physical activityFFZl  p .  p,$D  0f  6 p8  B  A 4Overweight (BMI 25 kg/m2)n.  BH  ? @ <Non-overweight (BMI <25 kg/m2)\f  6  p`B  0D `  `B   0D ` ZB ! s *D ` ` ZB " s *D ` l `0  /`0 ,$D  0ZB  s *Dt `0  -`0 ,$D  0$  B  v  *Mild to moderate hyperglycemia (A1C <9.0%)B+$'  f  6 0 4  B    B Marked hyperglycemia (A1C 9.0%):"  `B  0D `B  0D ZB  s *D ` ` ) 0 H  0޽h ? =_933+ # ___PPT10 + oD ' = @B D ' = @BA?%,( < +O%,( < +D' =%(%(D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*+%(D' =-o6Bwipe(up)*<3<*+D' =%(D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*/%(D' =-o6Bwipe(up)*<3<*/D' =%(D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*.%(D' =-o6Bwipe(up)*<3<*.+3  *4@r(  4f *4 0f" l p #4p,$D  0~ @p   4 @p ,$D  0f 4 6@p  4 6 0  NAdd a drug from a different class or Use insulin alone or in combination with:(ONv 4 6  `  R biguanide insulin secretagogue insulin sensitizer* alpha-glucosidase inhibitorTS! 1>     [ 4  [,$D  0` 4 0 H 4 <p [,$D  0 Timely adjustments to and/or additions of oral antihyperglycemic agents and/or insulin should be made to attain target A1C within 6 to 12 months /Q`B 4 0D@ @ T @   4#   Z" 4 s *@   4 <0 { @  HIf not at target 4 <P 0v,$D 0 ?* When used in combination with insulin, insulin sensitizers may increase the risk of edema or CHF. The combination of an insulin sensitizer and insulin is currently not an approved indication in Canada.2G g Vuj   %4# ,$D  0    4  ,$D  0` 4 0 x&  4 0h f 4Overweight (BMI 25 kg/m2)nZB  4 s *D@ ~@   4 ,$D  0N  4 f  4 6& 4 B Z  *Mild to moderate hyperglycemia (A1C <9.0%)D+$'  `B 4 0D@ @ \t ++ $4++,$D  0f 4 6++ 4 6 d ,Biguanide alone or in combination with 1 of:0-, $b 4 6 kP P insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitorTQ!*%,   8   )4 b &4 TԔԔ8c8c?  4 <`  ,$ 0 o)L I F E S T Y L E**)H 4 0޽h ? ̙33@8___PPT10+"]>D' = @B D' = @BA?%,( < +O%,( < +D' =%(%(D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%4%(D' =-o6Bwipe(up)*<3<*%4D' =%(D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*#4%(D' =-o6Bwipe(up)*<3<*#4+N+ MMeYM( w df e 0f"  2d 6U p VDose-Effect Relationship"*4 3d # {M4 4d # d5 5d 6U e VDose-Effect Relationship"* 6d 6P U Y VDose-Effect Relationship"*4 7d # `  8d 6U  ~k QRiddle M. Combining"  9d 6U  mXk n sulfonylureas"   :d 6U  Kk X and other oral agents. "  ;d 6U  o. k K Am J of Med$   d #  & ?d 6p.U "   KGraph of theoretical dose-effect relationship for many drugs, showing that "LK @d 6(3U  =Q Hhalf-maximal dosages yield far more than 50% of the therapeutic effects "IH Ad 67U E Gand that side effects can increase as the dosage nears maximal levels. "HGB8 W  eW n@ 69  d69 @ 69  d69 B Bd 3 6NB Cd 3 NeB Dd 3 e|B Ed 3 |B Fd 3 B Gd 3 B Hd 3 B Id 3 B Jd 3 !B Kd 3 #+B Ld 3 %+BB Md 3 'BZB Nd 3 )ZqB Od 3 +qB Pd 3 -B Qd 3 /B Rd 3 1B Sd 3 3B Td 3 5B Ud 3 8B Vd 3 :+B Wd 3 <+CB Xd 3 ?CZB Yd 3 AZqB Zd 3 CqB [d 3 FB \d 3 HB ]d 3 KB ^d 3 MB _d 3 O B `d 3 Q  B ad 3 S 7B bd 3 U7OB cd 3 WOfB dd 3 Yf}B ed 3 [}B fd 3 ]B gd 3 _B hd 3 `B id 3 bB jd 3 dB kd 3 e,B ld 3 g,CB md 3 hC[B nd 3 i[rB od 3 krB pd 3 lB qd 3 mB rd 3 mB sd 3 nB td 3 oB ud 3 p B vd 3 q , B wd 3 q, D B xd 3 rD [ B yd 3 s[ r B zd 3 sr  B {d 3 t  B |d 3 t  B }d 3 t  B ~d 3 u  B d 3 u  B d 3 u ! B d 3 u! 9 N d S jJ69 @ . N: 9  d. N: 9 < d # . : 9 < d # . : < d # . g : < d # .  : D < d # . : < d # . r: < d # . : O< d # . : < d # . }: < d # . ,: Z< d # . : < d # . : < d # . 7: f< d # . : < d # . : < d # . N: q< d #   < d # r< d #   C< d # E 7t Z< d #  ;< d # +@ N Z dN Z< d # NZ< d # NCZ< d # fNZ< d # NZ< d #  N8Z< d # [NZ< d # NZ< d # N- Z< d # P N~ Z< d #  N Z< d #  N! Z< d # D Ns Z< d #  N Z< d #  N Z< d # 9 Nh Z< d #  N Z< d #  N ZHB d C jJ78< d #  d 6ZU  GMaximal$ < d # } d 6_U *} L Half-maximal$  < d #  g  d 6PeU  u  L Half-maximal$  < d # g   d 6iU    GMaximal$ < d # 9 e  d 6hU s   RTherapeutic effect$ < d # i%g  d 6\sU f  K Side effect$  @ -  d-  d tBC#DEF3f # @` - B d 3 3f ! B d 3 3f ! B d 3 3f  7! B d 3 3fO f B d 3 3f}  B d 3 3f  B d 3 3f  B d 3 3f  !  d tBC#DEF3f # @`8 O B d 3 3ff ~ B d 3 3f  B d 3 3f  B d 3 3f B d 3 3f! 8 B d 3 3fP g B d 3 3f~ B d 3 3f B d 3 3f B d 3 3f !  d tBC#DEF3f # @`9 P B d 3 3fg  B d 3 3f B d 3 3f B d 3 3f B d 3 3f" 9  d tBC#DEF3f # @`Q h B d 3 3f B d 3 3f B d 3 3f B d 3 3f " B d 3 3f: Q B d 3 3fh B d 3 3f B d 3 3f B d 3 3f B d 3 3f# : B d 3 3fR i B d 3 3f B d 3 3f B d 3 3f  d tBC#DEF3f # @`  # B d 3 3f; R B d 3 3fi   d tBC#DEF3f # @`   d BCDEF&3f  @`   d tB C#DEF3f #  @`  B d 3 3f / B d 3 3fG ^ B d 3 3fu~   d tBC#DEF3f # @`r  B d 3 3fr  B d 3 3fg ~ B d 3 3f0[ Gr  d tBC#DEF3f # @`_O vr  d tB#C#DEF3f ## @`D g  d tB#CDEF3f # @`8 O  d tB#CDEF3f # @`, D  d tBC#DEF3f # @`  %8  d tB#C/DEF3f /# @`0S!  d tB#C#DEF3f ## @`Sv d tBC/DEF3f /  @` d tB#C#DEF3f ## @` d tBCDEF3f  @` d <LU W* FEffect$< d # Q i  d 68U    DDose$ d B( CDE8F@R0v_T#`>>]J .(  @B! H d 0޽h ? ̙33y___PPT10Y+D=' = @B +9* 88h|8( w hf h 0f"  h 6U w QDose-Response Curve"*4 h # {4 h # d h 60U k QDose-Response Curve"* h 6U ` QDose-Response Curve"*4  h # `   h 6dU  ~k QRiddle M. Combining"   h 6U  mXk n sulfonylureas"    h 6xU  Kk X and other oral agents. "   h 6гU  o. k K Am J of Med$   h 6lU  * k U. 2000; 108(6A):15S-22S"  h 6U  } k =.  4 h # # h 60U F+ l.Dose-response curve showing GI related effects"/.f8   Th @   Rh B h 3 B h 3 B h 3 AB h 3 ApB h 3 pB h 3 B h 3 B h 3 B h 3 !NB h 3 "N|B h 3 $|B h 3 'B h 3 )B h 3 ++B  h 3 ,+ZB !h 3 /ZB "h 3 1B #h 3 4B $h 3 5B %h 3 87B &h 3 :7fB 'h 3 =fB (h 3 ?B )h 3 AB *h 3 CB +h 3 FCB ,h 3 HCrB -h 3 KrB .h 3 MB /h 3 OB 0h 3 Q B 1h 3 S OB 2h 3 VO~B 3h 3 X~B 4h 3 YB 5h 3 [B 6h 3 ], B 7h 3 _, [ B 8h 3 a[  B 9h 3 b  B :h 3 d  B ;h 3 e  B h 3 ig  B ?h 3 k  B @h 3 k  B Ah 3 m  B Bh 3 n E B Ch 3 oE s B Dh 3 os  B Eh 3 p  B Fh 3 q  B Gh 3 r " B Hh 3 r" Q B Ih 3 sQ t B Jh 3 st  B Kh 3 t  B Lh 3 t  B Mh 3 t . B Nh 3 u. ] B Oh 3 u]  B Ph 3 u  B Qh 3 u  N Sh S jJ 8 6  h6 < Uh # Y | < Vh #   C < Wh #  < Xh #  + f< Yh # t e < Zh #  e0HB [h C jJ HB \h C jJ  HB ]h C jJq  HB ^h C jJqHB _h C jJqHB `h C jJq< ah # f bh 6U %  B30$ < ch # 8  dh 6PU %8  B20$ < eh #  ~  fh 6U % r  B10$ HB gh C jJ  HB hh C jJ HB ih C jJ HB jh C jJ  HB kh C jJ < lh # N   mh 6U }9   A0$ < nh #   P  oh 6LU D9  C500$ < ph #   Q  qh 6,U D 9 D  D1000$ < rh #   R  sh 6U E 9 E  D1500$ < th #   R  uh 6W F9 F  D2000$ < vh # <   wh 6W v9 v  D2500$ < xh #  }"  yh 6H W  e!  A0$ < zh # g   {h 6W  q  C0.5$ < |h # |Z  }h 6W f  C1.0$ < ~h # |B h 6`W ef C1.5$ < h # |6 h 6W df C2.0$ < h #  :  h 6`"W " " :  DDose$  h <L'W $  XGI Distress Patients (%)$  h <|+W *  |Reduction vs. placebo, HbA$  h </W 6 C1c $ h <p5W * C(%)$  h B CHDE8F@3fH $] l. t : @e  h B C_DE8F@__]G0^$jG/2 x ^   @f B2 h 3 O8~B2 h 3  " ZB2 h 3   B2 h 3 ^6B2 h 3 HB h C jJHB h C jJ HB h C jJ! - H h 0޽h ? ̙33y___PPT10Y+D=' = @B + / $  z(  f  0f"  l P`  P` ,$D  0B zB 0D@ A \,$D  0t P`  P` ,$D  0(  # ,$D  0f p 6 " q 6?W p <Non-overweight (BMI <25 kg/m2)\   ,$D  0f n 6$ o BFW Z  *Mild to moderate hyperglycemia (A1C <9.0%)B+$'  `B  0D@ @ f r 6 P`0  s 6JW  P`` p1 or 2 antihyperglycemic agents from different classes j90 M t 6tTW   ` [ biguanide insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor"\!\>    |l 1 |  1|,$D  0Vt @ 1 |,$D  0f  6Pxd  B[W @ Timely adjustments to and/or additions of oral antihyperglycemic agents and/or insulin should be made to attain target A1C within 6 to 12 months /Qt @ pz  @ pz ,$D  0`B { 0D ? @  @ pz  #  @ pz ,$D  0f u 6 @ pz  v 6`W  0   NAdd a drug from a different class or Use insulin alone or in combination with:(ONv w 6eW   b  R biguanide insulin secretagogue insulin sensitizer* alpha-glucosidase inhibitorTS! 1>    `"  0  O  BnW w  ? HIf not at target  <rW `0 >H* When used in combination with insulin, insulin sensitizers may increase the risk of edema or CHF. The combination of an insulin sensitizer and insulin is currently not an approved indication in Canada. May be given as a combined formulation: rosiglitazone and metformin (Avandamet TM)%G o Og o g PV   F     ~b  NԔԔ8c8c?   6~W  ,$ 0 o)L I F E S T Y L E**)H  0޽h ? ̙33@8___PPT10+RD' = @B D' = @BA?%,( < +O%,( < +D' =%(%(D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D' =-o6Bwipe(up)*<3<*D' =%(D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D' =-o6Bwipe(up)*<3<*+r. dH B(  Hf dH 0f" Al  bH,$D  0  6 ]H  6,$D  0`B GH 0D@ @ 6f JH 6  < KH BW  B Marked hyperglycemia (A1C 9.0%)B"   f RH 60V SH 6ĎW L  f2 antihyperglycemic agents from different classes D42!M UH 6pW kH  [ biguanide insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor"\!\>    l d. cHd.,$D  0t  d [HP d0 ,$D  0f AH 6 d BH 6W 0 ^ FAdd an oral antihyperglycemic agent from a different class or insulin*GG * [ MH  [.,$D  0` NH 0 H OH <W [,$D  0 Timely adjustments to and/or additions of oral antihyperglycemic agents and/or insulin should be made to attain target A1C within 6 to 12 months /Q`B TH 0D@ @ \ `" WH 0p ?  XH BW { p /  HIf not at target \H < W D`  >H* When used in combination with insulin, insulin sensitizers may increase the risk of edema or CHF. The combination of an insulin sensitizer and insulin is currently not an approved indication in Canada. May be given as a combined formulation: rosiglitazone and metformin (Avandamet TM)%G o Og o g PV   F   _H  ~b `H NԔԔ8c8c?  aH 6TW  ,$ 0 o)L I F E S T Y L E**)H H 0޽h ? ̙33@8___PPT10+MdD' = @B D' = @BA?%,( < +O%,( < +D' =%(%(D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*bH%(D' =-o6Bwipe(up)*<3<*bHD' =%(D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*cH%(D' =-o6Bwipe(up)*<3<*cH+T- 'X$  (  Xf 'X 0f" l  !X,$D  0  ` X  `,$D  0`B X 0D@ @ `f X 6  R  X BW \ D Marked hyperglycemia (A1C 9.0%) V# f X 6` X 6W ~n | Basal and/or preprandial insulin!!  - X <dW D0 * When used in combination with insulin, insulin sensitizers may increase the risk of edema or CHF. The combination of an insulin sensitizer and insulin is currently not an approved indication in Canada. * * If using preprandial insulin, do not add an insulin secretagogue.JG o Bg >V  F   X  ~b X NԔԔ8c8c?  X 6W  ,$ 0 o)L I F E S T Y L E**)l d^ &Xd^,$D  0@ d  #Xd f X 6d `B X 0D @ @  X 6W  0t  Z Intensify insulin regimen or add!!R X 6W   `  T biguanide insulin secretagogue** insulin sensitizer* alpha-glucosidase inhibitor.U!T>    `" X 0 o~@ [^ %X[^dN P [^ $X P [^f  X 6  X HH  X BW  P [^,$D  0 Timely adjustments to and/or additions of oral antihyperglycemic agents and/or insulin should be made to attain target A1C within 6 to 12 months /Q X B`W  {  ` HIf not at targetH X 0޽h ? ̙33@8___PPT10+@ED' = @B D' = @BA?%,( < +O%,( < +D' =%(%(D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*!X%(D' =-o6Bwipe(up)*<3<*!XD' =%(D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*&X%(D' =-o6Bwipe(up)*<3<*&X++, 9*1*0Ab )(  f b 0f" X  00   <W f  }EClinical assessment and initiation of nutrition and physical activityFF X  0   <X H  *Mild to moderate hyperglycemia (A1C <9.0%)B+$ '    X  0@`*   <|X  4Overweight (BMI 25 kg/m2)n         < X   <Non-overweight (BMI <25 kg/m2)\    X   0  X   0@`   <4X I` ,Biguanide alone or in combination with 1 of:0-,   $N  <X   R insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor@G! R  ,   X  0  Z  <TX  H n1 or 2 antihyperglycemic agents from different classesB8  0   <%X P *  ^ biguanide insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor XR! ]   >   X  0    00X    SAdd a drug from a different class or Use insulin alone or in combination with: 8TR  4  0 4X F V R biguanide insulin secretagogue insulin sensitizer* alpha-glucosidase inhibitor S!S >    X & 0p$ ' <:X @c B Marked hyperglycemia (A1C 9.0%)8"     ( <    , <VX V z Basal and/or preprandial insulin!!    8 <dYX  0   P !!X 9 0 ` : <]X  `   FAdd an oral antihyperglycemic agent from a different class or insulin*&GF  * ; <4bX    ` Intensify insulin regimen or add$!  t < <gX  3 Z biguanide insulin secretagogue** insulin sensitizer* alpha-glucosidase inhibitorL! )! [ >   RB G s *D tF  F  5  `$ Z" 6 s * >  7 <rX u kF  HIf not at target RB H s *D tF  F  =  b$ Z" > s * >  ? <\uX u kF  HIf not at target RB I s *D T T tF  F  @  " $ Z" A s * >  B <zX u kF  HIf not at target RB J s *D`RB K s *D`LB L c $D``LB M c $D@@`RB N s *D@@LB O c $D@RB P s *DLB Q c $D @ @ RB R s *D`PPRB S s *D`P P LB T c $D`PP `LB U c $D`RB V s *DPPRB W s *DQ Q RB X s *D PP tF  F  C  0$ Z" D s * >  E <X u kF  HIf not at target X Z 0@V [ <`X S Timely adjustments to and/or additions of oral antihyperglycemic agents and/or insulin should be made to attain target A1C within 6 to 12 months /Q|b ` TԔԔ8c8c? a <X P,$ 0 q)L I F E S T Y L E,*)  H  0޽h ? ̙33y___PPT10Y+D=' = @B + 0 P=( w f  0f"   T`X  8cԔ8c?"` X    TX  ԔԔ8c8c?m y U Key Changes $  H  0޽h ? ̙33y___PPT10Y+D=' = @B +U %p ( w  f   0f" \   ZX ԔԔ8c8c?n xCanadian Diabetes Association 2003 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada>@9XZx   0X `Z t This material has been reviewed by the Canadian Diabetes Association for its medical and scientific accuracy. Presence of the Canadian Diabetes Association Partners in Progress mark does not constitute an endorsement of the products or services of GlaxoSmithKline Inc.*    h   C @A(Box For Intros copyp    ZHX ԔԔ8c8c?L  m#Getting to Goal in Type 2 Diabetes.$#6,`   C 8A  Partners logo ap `0H   0޽h ? ̙33y___PPT10Y+D=' = @B + <K0 F(  f  0f" h  C @A(Box For Intros copyRp 0  3 rX 1ԔԔ8c8c?x"/  *Supplementary Slides: Key Recommendations 4+ *,, + N  63f ;޽h ? fr̙33y___PPT10Y+D=' = @B +@ TI(  Tf T 0f"  T N 9.0%), antihyperglycemic agents should be initiated concomitant with lifestyle counselling [Grade D, Consensus]. Z0n2 2ee/ee\eeeeg g ggt#  K  i  7     T 3 rxX 1ԔԔ8c8c?@; tRecommendation 14 ((  H T 0޽h ? ̙33y___PPT10Y+D=' = @B +|A X3(  Xf X 0f" o X N(X ԔԔ8c8c?B0^ If glycemic targets are not attained when a single antihyperglycemic agent is used initially, an antihyperglycemic agent or agents from other classes should be added. The lag period before adding other agent(s) should be kept to a minimum, taking into account the pharmacokinetics of the different agents. Timely adjustments to and/or additions of antihyperglycemic agents should be made in order to attain target A1C within 6 to 12 months [Grade D, Consensus]. t0n2eeeeg  (      `   X 3 rX 1ԔԔ8c8c?@; tRecommendation 24 ((  H X 0޽h ? ̙33y___PPT10Y+D=' = @B + B `l(  `f ` 0f"  ` 3 rX 1ԔԔ8c8c?@; tRecommendation 34 ((   ` NX ԔԔ8c8c?0P/ * This choice of antihyperglycemic agent(s) should take into account the individual and the following factors: Unless contraindicated, a biguanide (metformin) should be the primary drug used in overweight patients [Grade A, Level 1A]; and Other classes of antihyperglycemic agents may be used either alone or in combination to attain glycemic targets, with consideration given to the information in Table 1 and Figure 1 [Grade D, Consensus for the order of antihyperglycemic agents listed in Figure 1]. 0n2lee g g e  e  e eeQeee  M        R    =  s    H ` 0޽h ? ̙33y___PPT10Y+D=' = @B +-C TLd(  df d 0f"  d 3 r_ 1ԔԔ8c8c?@; tRecommendation 44 ((    d N`_ ԔԔ8c8c?B0g  `In people with type 2 diabetes, if individual treatment goals have not been reached with a regimen of nutrition therapy, physical activity and sulfonylurea [Grade A, Level 1A], sulfonylurea plus metformin [Grade A, Level 1A] or other oral antihyperglycemic agents [Grade D, Consensus], insulin therapy should be initiated to improve glycemic control. a0n2eeee(eeCegn   #  M     H d 0޽h ? ̙33y___PPT10Y+D=' = @B + D   0h (  hf h 0f"  h 3 rT_ 1ԔԔ8c8c?@; tRecommendation 54 ((   h Nx_ ԔԔ8c8c?0o nCombining insulin and the following oral antihyperglycemic agents (listed in alphabetical order) has been shown to be effective in people with type 2 diabetes: alpha-glucosidase inhibitors (acarbose) [Grade A, Level 1A] biguanide (metformin) [Grade A, Level 1A] Insulin secretagogues (sulfonylureas) [Grade A, Level 1A] Insulin sensitizers (thiazolidinediones) [Grade A, Level 1A] (The combination of an insulin sensitizer plus insulin is currently not an approved indication in Canada.) 0n2?0n2j0n2@0n2v0(2gg* g  g gggg ($g$$g$(g(,,+0g00g0p0g00e04g4P)  f                               H h 0޽h ? ̙33y___PPT10Y+D=' = @B +E D<Pl(  lf l 0f"  l 3 rd4_ 1ԔԔ8c8c?@; tRecommendation 64 ((   l NB_ ԔԔ8c8c?B`s Insulin may be used as initial therapy in type 2 diabetes [Grade A, Level 1A], especially in cases of marked hyperglycemia (A1C > 9.0%) [Grade D, Consensus]. 0n2:ee3eeeeeg   H l 0޽h ? ̙33y___PPT10Y+D=' = @B +QF xppp(  pf p 0f"  p 3 r_ 1ԔԔ8c8c?@; tRecommendation 74 ((  D p NS_ ԔԔ8c8c?B0Z  To safely achieve optimal postprandial glycemic control, mealtime insulin lispro or insulin aspart is preferred over regular insulin [Grade B, Level 2]. 0n2 2eeegg g n'       6  H p 0޽h ? ̙33y___PPT10Y+D=' = @B +G tI(  tf t 0f"  t 3 r`_ 1ԔԔ8c8c?@; tRecommendation 84 ((   t Nf_ ԔԔ8c8c?B0;  When insulin given at night is added to oral antihyperglycemic agents, insulin glargine may be preferred over NPH to reduce overnight hypoglycemia [Grade B, Level 2] and weight gain [Grade B, Level 2 ]. 0n2 2eeeeegg g T-    s  H t 0޽h ? ̙33y___PPT10Y+D=' = @B +zH x1(  xf x 0f"  x 3 rr_ 1ԔԔ8c8c?@; tRecommendation 94 ((  m x NHx_ ԔԔ8c8c?B0T  All individuals with type 2 diabetes currently using or starting therapy with insulin or insulin secretagogues should be counselled about the recognition and prevention of drug-induced hypoglycemia [Grade D, Consensus]. 0n2 2eeegg g Ta       X  H x 0޽h ? ̙33y___PPT10Y+D=' = @B + ;K0 ^( w f  0f" h  C @A(Box For Intros copy H  3 r_ 1ԔԔ8c8c?o+  BSupplementary Slides: Alternate Animation for Treatment Algorithm 4C B,, C N  63f ;޽h ? fr̙33y___PPT10Y+D=' = @B +*I **AC)( 3l  f C 0f" X  00   <?Ef  }EClinical assessment and initiation of nutrition and physical activityFF X  0   <_ H  *Mild to moderate hyperglycemia (A1C <9.0%)B+$ '    X  0@`*  <_  4Overweight (BMI 25 kg/m2)n        <4_   <Non-overweight (BMI <25 kg/m2)\    X   0  X   0@`    <_ I` ,Biguanide alone or in combination with 1 of:0-,   $N   <:E  R insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor@G! R  ,   X   0  Z  <(_  H n1 or 2 antihyperglycemic agents from different classesB8  0   <_ P *  ^ biguanide insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor XR! ]   >   X  0    0_    SAdd a drug from a different class or Use insulin alone or in combination with: 8TR  4  0_ F V R biguanide insulin secretagogue insulin sensitizer* alpha-glucosidase inhibitor S!S >    X  0p$  <_ @c B Marked hyperglycemia (A1C 9.0%)8"      <4_ E  P !!X  0`@  <_ 0 % f2 antihyperglycemic agents from different classes 042  !  <4_  Tp ^ biguanide insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor VR! ]  >     <_ V z Basal and/or preprandial insulin!!     <\_  0   P !!X  0 `  <_  `   FAdd an oral antihyperglycemic agent from a different class or insulin*&GF  *  <_    ` Intensify insulin regimen or add$!  t  <_  3 Z biguanide insulin secretagogue** insulin sensitizer* alpha-glucosidase inhibitorL! )! [ >   RB  s *D tF  F     `$ Z" ! s * >  " <X` u kF  HIf not at target RB # s *D tF  F  $  b$ Z" % s * >  & <8_ u kF  HIf not at target RB ' s *D T T tF  F  (  " $ Z" ) s * >  * < ` u kF  HIf not at target RB + s *D`RB , s *D`LB - c $D``LB . c $D@@`RB / s *D@@LB 0 c $D@RB 1 s *DLB 2 c $D @ @ RB 3 s *D`PPRB 4 s *D`P P LB 5 c $D`PP `LB 6 c $D`RB 7 s *DPPRB 8 s *DQ Q RB 9 s *D PP tF  F  :  0$ Z" ; s * >  < <h` u kF  HIf not at target X > 0@V ? <` S Timely adjustments to and/or additions of oral antihyperglycemic agents and/or insulin should be made to attain target A1C within 6 to 12 months /Qvb A NԔԔ8c8c?  B 6` P,$ 0 q)L I F E S T Y L E,*)  B  s *f޽h ? ̙33y___PPT10Y+D=' = @B +T*J K0 c)[)@A((  f A 0f" X  00   <D'` f  }EClinical assessment and initiation of nutrition and physical activityFF X  0   <,` H  *Mild to moderate hyperglycemia (A1C <9.0%)B+$ '    X  0@`*  <2`  4Overweight (BMI 25 kg/m2)n     R  s *  X   0@`    <9` I` ,Biguanide alone or in combination with 1 of:0-,   $N   <?`   R insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor@G! R  ,   R   s *  X   0    0HH`    SAdd a drug from a different class or Use insulin alone or in combination with: 8TR  4  0M` F V R biguanide insulin secretagogue insulin sensitizer* alpha-glucosidase inhibitor S!S >    RB  s *D T T LB  c $D@ @RB  s *DLB  c $D$@ @ RB  s *D`PPRB  s *D`P P LB  c $D`P`LB  c $D_RB @ s *DPQRB  s *DQ Q RB  s *D PP tF  F    0$ Z"  s * >   <TW` u kF  HIf not at target R  s *p.  <[` @c B Marked hyperglycemia (A1C 9.0%)B"        6b` E  P !!R ! s *`@ " <g` 0 % f2 antihyperglycemic agents from different classes 042  ! # <e`  T ^ biguanide insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor ZR! ]   >    $ <w` 3V z Basal and/or preprandial insulin!!    % 6y`  0   P !! & <}`  `   FAdd an oral antihyperglycemic agent from a different class or insulin*GG  *RB ' s *D R" ( s * `  ) <`  V$  HIf not at target 3RB * s *D R" + s * b  , <(`  X $  HIf not at target 3RB - s *D`RB . s *D`LB / c $D``LB 0 c $D3@@`RB 1 s *D@@R 2 s * ` 3 <@`    X Intensify insulin regimen or add!! t 4 <`  0 Z biguanide insulin secretagogue** insulin sensitizer* alpha-glucosidase inhibitorL! )! [ >     5 <`   <Non-overweight (BMI <25 kg/m2)\    Z 6 <l`  H n1 or 2 antihyperglycemic agents from different classesB8  0  7 <` P *  ^ biguanide insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor ZR! ]   >   R" 8 s * "   9 <x`   $  HIf not at target 3LB : c $D`Q `LB ;@ c $D@ X < 0@V = <` S Timely adjustments to and/or additions of oral antihyperglycemic agents and/or insulin should be made to attain target A1C within 6 to 12 months /Qvb ? NԔԔ8c8c?  @ 6` P,$ 0 q)L I F E S T Y L E,*)  B  s *f޽h ? ̙33y___PPT10Y+D=' = @B +$K 0 p(  f   0f" dz @p   @p ,$D  0`  0@p   0h` 0  NAdd a drug from a different class or Use insulin alone or in combination with:(ONp  0d`  `  R biguanide insulin secretagogue insulin sensitizer* alpha-glucosidase inhibitorTS! 1>    zz      ,$D  0`  0 x&   0` f 4Overweight (BMI 25 kg/m2)nZB   s *D@ ~@ z    ,$D  0N    `   0   <$` Z  *Mild to moderate hyperglycemia (A1C <9.0%)D+$'  ZB  s *D@ @ z [   [,$D  0`  0 H  <` [,$D  0 Timely adjustments to and/or additions of oral antihyperglycemic agents and/or insulin should be made to attain target A1C within 6 to 12 months /Qz ++  ++,$D  0 ++  ++,$D  0`  0++  0<` d ,Biguanide alone or in combination with 1 of:0-, $ZB  s *D@ @ \  0` kP P insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitorTQ!*%,   T @   #   Z"  s *@    <` { @  HIf not at target  <T` 2 ?* When used in combination with insulin, insulin sensitizers may increase the risk of edema or CHF. The combination of an insulin sensitizer and insulin is currently not an approved indication in Canada.2G g VuF     ~b  NԔԔ8c8c?   6a  ,$ 0 o)L I F E S T Y L E**)H  0޽h ? ̙33___PPT10y+•D]' = @B D' = @BA?%,( < +O%,( < +DO ' =%(%(D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<* %(D' =-o6Bwipe(up)*<3<* D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D' =-o6Bwipe(up)*<3<*D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D' =-o6Bwipe(up)*<3<*D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D' =-o6Bwipe(up)*<3<*D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D' =-o6Bwipe(up)*<3<*+*L ** AB)(  f B 0f" X  00   < a f  }EClinical assessment and initiation of nutrition and physical activityFF X  0   <Ta H  *Mild to moderate hyperglycemia (A1C <9.0%)B+$ '    X  0@`*  <a  4Overweight (BMI 25 kg/m2)n        <a   <Non-overweight (BMI <25 kg/m2)\    X   0  X   0@`    <`%a I` ,Biguanide alone or in combination with 1 of:0-,   $N   </a   R insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor@G! R  ,   X   0  Z  <(3a  H n1 or 2 antihyperglycemic agents from different classesB8  0   <` P *  ^ biguanide insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor XR! ]   >   X  0    0@a    SAdd a drug from a different class or Use insulin alone or in combination with: 8TR  4  0Da F V R biguanide insulin secretagogue insulin sensitizer* alpha-glucosidase inhibitor S!S >    X  0p$  <8Ka @c B Marked hyperglycemia (A1C 9.0%)8"      <Qa E  P !!X  0`@  <tNa 0 % f2 antihyperglycemic agents from different classes 042  !  <p[a  Tp ^ biguanide insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor VR! ]  >     <Dfa V z Basal and/or preprandial insulin!!     <ia  0   P !!X  0 `  <Lha  `   FAdd an oral antihyperglycemic agent from a different class or insulin*&GF  *  <ra    ` Intensify insulin regimen or add$!  t  <,xa  3 Z biguanide insulin secretagogue** insulin sensitizer* alpha-glucosidase inhibitorL! )! [ >   RB  s *D tF  F     `$ Z" ! s * >  " <xa u kF  HIf not at target RB # s *D tF  F  $  b$ Z" % s * >  & <a u kF  HIf not at target RB ' s *D T T tF  F  (  " $ Z" ) s * >  * < a u kF  HIf not at target RB + s *D`RB , s *D`LB - c $D``LB . c $D@@`RB / s *D@@LB 0 c $D@RB 1 s *DLB 2 c $D @ @ RB 3 s *D`PPRB 4 s *D`P P LB 5 c $D`PP `LB 6 c $D`RB 7 s *DPPRB 8 s *DQ Q RB 9 s *D PP tF  F  :  0$ Z" ; s * >  < <$a u kF  HIf not at target X > 0@V ? <̖a S Timely adjustments to and/or additions of oral antihyperglycemic agents and/or insulin should be made to attain target A1C within 6 to 12 months /Qvb @ NԔԔ8c8c?  A 6Xa P,$ 0 q)L I F E S T Y L E,*)  H  0޽h ? ̙33y___PPT10Y+D=' = @B +*M K0 ))`@A!)(  f A 0f" X  00   <Уa f  }EClinical assessment and initiation of nutrition and physical activityFF X  0   <@a H  *Mild to moderate hyperglycemia (A1C <9.0%)B+$ '    R  s *@`*  <a  4Overweight (BMI 25 kg/m2)n        <a   <Non-overweight (BMI <25 kg/m2)\    X   0  R   s *@`    <|a I` ,Biguanide alone or in combination with 1 of:0-,   $N   <`a   R insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor@G! R  ,   X   0  Z  <   X  0    0a    SAdd a drug from a different class or Use insulin alone or in combination with: 8TR  4  0da F V R biguanide insulin secretagogue insulin sensitizer* alpha-glucosidase inhibitor S!S >    R  s *p@  <a @c B Marked hyperglycemia (A1C 9.0%)T"        6Ta E  P !!R  s *`@  < a 0 % f2 antihyperglycemic agents from different classes 042  !  <xa  T ^ biguanide insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor ZR! ]   >     <c V z Basal and/or preprandial insulin!!     6c  0   P !!R  s * `  < c  `   FAdd an oral antihyperglycemic agent from a different class or insulin**GF  *  <c    d Intensify insulin regimen or add(!  t  <0c  3 Z biguanide insulin secretagogue** insulin sensitizer* alpha-glucosidase inhibitorL! )! [ >   RB  s *D R"   s * `  ! <  ( <@%c u kF  HIf not at target RB ) s *D`RB * s *D`LB + c $D``LB , c $D@@`RB - s *D@@LB . c $D@ RB / s *DLB 0 c $D$@ @ RB 1 s *D`PPRB 2 s *D`P P LB 3 c $D`P`LB 4 c $D`RB 5 s *DPPRB 6 s *DQ Q RB 7 s *D PP R" 8 s * 0  9 <-c  &$  HIf not at target 3LB : c $D`P `LB ; c $D@ @X = 0@V > <2c S Timely adjustments to and/or additions of oral antihyperglycemic agents and/or insulin should be made to attain target A1C within 6 to 12 months /Qvb ? NԔԔ8c8c?  @ 688c P,$ 0 q)L I F E S T Y L E,*)  H  0޽h ? ̙33y___PPT10Y+D=' = @B +'N (  f  0f" dz @ pz    @pz ,$D  0`  0@ pz   0@c 0   NAdd a drug from a different class or Use insulin alone or in combination with:(ONp  0Cc  b  R biguanide insulin secretagogue insulin sensitizer* alpha-glucosidase inhibitorTS! 1>    6z d  d,$D  0   ,$D  0`   0    0$Lc p <Non-overweight (BMI <25 kg/m2)\B  B s *D> ? d,$D  0rz    ,$D  0`   0  <Sc Z  *Mild to moderate hyperglycemia (A1C <9.0%)B+$'  ZB  s *D@ @ Pz @   1|,$D  0`  0Px^  <Zc @ Timely adjustments to and/or additions of oral antihyperglycemic agents and/or insulin should be made to attain target A1C within 6 to 12 months /Qz P``  `P`,$D  0+ P``  P``,$D   0`  0P`0   0ac P`` p1 or 2 antihyperglycemic agents from different classes j90 G  0\hc  ` [ biguanide insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor"\!\>    ZB  s *D? @ Z"  s * O  <nc w  ? HIf not at target  <sc ~< @J* When used in combination with insulin, insulin sensitizers may increase the risk of edema or CHF. The combination of an insulin sensitizer and insulin is currently not an approved indication in Canada. May be given as a combined formulation: rosiglitazone and metformin (Avandamet TM) &G o Og o g PV   F     ~b  NԔԔ8c8c?   6<c  ,$ 0 o)L I F E S T Y L E**)H  0޽h ? ̙33___PPT10y+o%D]' = @B D' = @BA?%,( < +O%,( < +DO ' =%(%(D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<* %(D' =-o6Bwipe(up)*<3<* D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D' =-o6Bwipe(up)*<3<*D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D' =-o6Bwipe(up)*<3<*D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D' =-o6Bwipe(up)*<3<*D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D' =-o6Bwipe(up)*<3<*+*O **AB)(  f B 0f" X  00   <   X  0    0(c    SAdd a drug from a different class or Use insulin alone or in combination with: 8TR  4  0c F V R biguanide insulin secretagogue insulin sensitizer* alpha-glucosidase inhibitor S!S >    X  0p$  < c @c B Marked hyperglycemia (A1C 9.0%)8"      <c E  P !!X  0`@  <0c 0 % f2 antihyperglycemic agents from different classes 042  !  <c  Tp ^ biguanide insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor VR! ]  >     <c V z Basal and/or preprandial insulin!!     <|c  0   P !!X  0 `  <c  `   FAdd an oral antihyperglycemic agent from a different class or insulin*&GF  *  <,c    ` Intensify insulin regimen or add$!  t  <Dd  3 Z biguanide insulin secretagogue** insulin sensitizer* alpha-glucosidase inhibitorL! )! [ >   RB  s *D tF  F     `$ Z" ! s * >  " <d u kF  HIf not at target RB # s *D tF  F  $  b$ Z" % s * >  & <$c u kF  HIf not at target RB ' s *D T T tF  F  (  " $ Z" ) s * >  * <Hc u kF  HIf not at target RB + s *D`RB , s *D`LB - c $D``LB . c $D@@`RB / s *D@@LB 0 c $D@RB 1 s *DLB 2 c $D @ @ RB 3 s *D`PPRB 4 s *D`P P LB 5 c $D`PP `LB 6 c $D`RB 7 s *DPPRB 8 s *DQ Q RB 9 s *D PP tF  F  :  0$ Z" ; s * >  < <d u kF  HIf not at target X > 0@V ? <\d S Timely adjustments to and/or additions of oral antihyperglycemic agents and/or insulin should be made to attain target A1C within 6 to 12 months /Qvb @ NԔԔ8c8c?  A 6|!d P,$ 0 q)L I F E S T Y L E,*)  H  0޽h ? ̙33y___PPT10Y+D=' = @B +`*P K0 o)g)@A((  f A 0f" X  00   <<(d f  }EClinical assessment and initiation of nutrition and physical activityFF X  0   < -d 3H  *Mild to moderate hyperglycemia (A1C <9.0%)B+$ '    R  s *@`*  <L2d  4Overweight (BMI 25 kg/m2)n        <p9d 3  <Non-overweight (BMI <25 kg/m2)\    X   0  R   s *@`    <X@d I` ,Biguanide alone or in combination with 1 of:0-,   $N   <   X  0    0Xd 3   SAdd a drug from a different class or Use insulin alone or in combination with: 8TR  3R  s *p.  <8cd @c B Marked hyperglycemia (A1C 9.0%)B"       6id E  P !!R  s *`@  <     <Hxd V z Basal and/or preprandial insulin!!     6   RB  s *D R"  s * `    <d  V$  HIf not at target 3RB ! s *D R" " s * b  # <Ԟd  X $  HIf not at target RB $ s *D T T R" % s * "   & <@d 3  $  HIf not at target 3RB ' s *D`RB ( s *D`RB ) s *D@@LB * c $D@ RB + s *DLB , c $D$@ @ RB - s *D`PPRB . s *D`P P LB / c $D`P`LB 0 c $D`RB 1 s *DPPRB 2 s *DQ Q RB 3 s *D PP R" 4 s * 0  5 <@d  &$  HIf not at target 3LB 6 c $D`P `LB 7 c $D@ @X 9 0@V : <Hd S Timely adjustments to and/or additions of oral antihyperglycemic agents and/or insulin should be made to attain target A1C within 6 to 12 months /Q4 ; 0d 3F V R biguanide insulin secretagogue insulin sensitizer* alpha-glucosidase inhibitor S!S >    LB < c $D`<`LB = c $D@@`LB > c $D`@`vb ? NԔԔ8c8c?  @ 6td P,$ 0 q)L I F E S T Y L E,*)  H  0޽h ? ̙33y___PPT10Y+D=' = @B +^Q (  f  0f" z  d  P d0 ,$D  0`  0 d   0    Z"  s *p ?   <d { p /  HIf not at target  <Dd < >H* When used in combination with insulin, insulin sensitizers may increase the risk of edema or CHF. The combination of an insulin sensitizer and insulin is currently not an approved indication in Canada. May be given as a combined formulation: rosiglitazone and metformin (Avandamet TM)%G o Og o g PV   F     ~b  NԔԔ8c8c?   6d  ,$ 0 o)L I F E S T Y L E**)H  0޽h ? ̙33  ___PPT10 +QDgD ' = @B D ' = @BA?%,( < +O%,( < +D ' =%(%(D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D' =-o6Bwipe(up)*<3<*D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<* %(D' =-o6Bwipe(up)*<3<* D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D' =-o6Bwipe(up)*<3<*D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<* %(D' =-o6Bwipe(up)*<3<* +*R **AB)(  f B 0f" X  00   <e f  }EClinical assessment and initiation of nutrition and physical activityFF X  0   <@e H  *Mild to moderate hyperglycemia (A1C <9.0%)B+$ '    X  0@`*  < e  4Overweight (BMI 25 kg/m2)n        <e   <Non-overweight (BMI <25 kg/m2)\    X   0  X   0@`    <\e I` ,Biguanide alone or in combination with 1 of:0-,   $N   <He   R insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor@G! R  ,   X   0  Z  <$e  H n1 or 2 antihyperglycemic agents from different classesB8  0   <*e P *  ^ biguanide insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor XR! ]   >   X  0    0|5e    SAdd a drug from a different class or Use insulin alone or in combination with: 8TR  4  0D9e F V R biguanide insulin secretagogue insulin sensitizer* alpha-glucosidase inhibitor S!S >    X  0p$  <?e @c B Marked hyperglycemia (A1C 9.0%)8"      <0Fe E  P !!X  0`@  <Ie 0 % f2 antihyperglycemic agents from different classes 042  !  <Oe  Tp ^ biguanide insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor VR! ]  >     <Te V z Basal and/or preprandial insulin!!     <_e  0   P !!X  0 `  <\ce  `   FAdd an oral antihyperglycemic agent from a different class or insulin*&GF  *  <ie    ` Intensify insulin regimen or add$!  t  <hoe  3 Z biguanide insulin secretagogue** insulin sensitizer* alpha-glucosidase inhibitorL! )! [ >   RB  s *D tF  F     `$ Z" ! s * >  " <Tte u kF  HIf not at target RB # s *D tF  F  $  b$ Z" % s * >  & <(}e u kF  HIf not at target RB ' s *D T T tF  F  (  " $ Z" ) s * >  * <He u kF  HIf not at target RB + s *D`RB , s *D`LB - c $D``LB . c $D@@`RB / s *D@@LB 0 c $D@RB 1 s *DLB 2 c $D @ @ RB 3 s *D`PPRB 4 s *D`P P LB 5 c $D`PP `LB 6 c $D`RB 7 s *DPPRB 8 s *DQ Q RB 9 s *D PP tF  F  :  0$ Z" ; s * >  < <xe u kF  HIf not at target X > 0@V ? < e S Timely adjustments to and/or additions of oral antihyperglycemic agents and/or insulin should be made to attain target A1C within 6 to 12 months /Qvb @ NԔԔ8c8c?  A 6e P,$ 0 q)L I F E S T Y L E,*)  H  0޽h ? ̙33y___PPT10Y+D=' = @B +`*S K0 o)g) @B((  f B 0f" X  00   <e f  }EClinical assessment and initiation of nutrition and physical activityFF X  0   <e 3H  *Mild to moderate hyperglycemia (A1C <9.0%)B+$ '    R  s *@`*  < e  4Overweight (BMI 25 kg/m2)n        <@e 3  <Non-overweight (BMI <25 kg/m2)\    X   0  R   s *@`    <Pe I` ,Biguanide alone or in combination with 1 of:0-,   $N   <e   R insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor@G! R  ,   X   0  Z  <e 3 H n1 or 2 antihyperglycemic agents from different classesB8  0   <e 3P *  ^ biguanide insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor ZR! ]   >   X  0    0e 3   SAdd a drug from a different class or Use insulin alone or in combination with: 8TR  R  s *p.  <|e @c B Marked hyperglycemia (A1C 9.0%)B"       6 e E  P !!R  s *`@  <     <e V z Basal and/or preprandial insulin!!     6e  0   P !!R  s * `  <e  `   FAdd an oral antihyperglycemic agent from a different class or insulin**GF  *  <Dg    d Intensify insulin regimen or add(!  t  <g  3 Z biguanide insulin secretagogue** insulin sensitizer* alpha-glucosidase inhibitorL! )! [ >   RB  s *D R"  s * `    < g  V$  HIf not at target RB ! s *D R" " s * b  # <(g  X $  HIf not at target 3RB $ s *D T T R" % s * "   & <Xg 3  $  HIf not at target 3RB ' s *D`RB ( s *D`RB ) s *D@@LB * c $D@ RB + s *DLB , c $D$@ @ RB - s *D`PPRB . s *D`P P LB / c $D`P`LB 0 c $D`RB 1 s *DPPRB 2 s *DQ Q RB 3 s *D PP R" 4 s * 0  5 <Xg  &$  HIf not at target 3LB 6 c $D`P `LB 7 c $D@ @X 9 0@V : <!g S Timely adjustments to and/or additions of oral antihyperglycemic agents and/or insulin should be made to attain target A1C within 6 to 12 months /Q4 ; 0'g 3F V R biguanide insulin secretagogue insulin sensitizer* alpha-glucosidase inhibitor S!S >    LB < c $D`<`LB = c $D@@`LB > c $D3`@`vb ? NԔԔ8c8c?  @ 6.g P,$ 0 q)L I F E S T Y L E,*)  H  0޽h ? ̙33y___PPT10Y+D=' = @B +HT @r(  f  0f" z  `   `,$D  0ZB  s *D@ @ ``  0  L  < E\ D Marked hyperglycemia (A1C 9.0%) V# z [  P [^,$D  0`  0 H   <    -  <X|E< * When used in combination with insulin, insulin sensitizers may increase the risk of edema or CHF. The combination of an insulin sensitizer and insulin is currently not an approved indication in Canada. * * If using preprandial insulin, do not add an insulin secretagogue.JG o Bg >V  F     ~b  NԔԔ8c8c?   6XE ,$ 0 o)L I F E S T Y L E**)H  0޽h ? ̙33  ___PPT10 +mLJD ' = @B D ' = @BA?%,( < +O%,( < +D ' =%(%(D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D' =-o6Bwipe(up)*<3<*D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<* %(D' =-o6Bwipe(up)*<3<* D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D' =-o6Bwipe(up)*<3<*D' =%(D3' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D' =-o6Bwipe(up)*<3<*+ 0 p,(  p^ pS 9   g  pc $(5g  pr  g  " H p 0޽h ? ̙33 0 Px,(  x^ xS 9   g  xc $:g  pr  g  " H x 0޽h ? ̙33  0   T (  ^ S 9   g   c $?g  pr  g  J P UKPDS 35 was a prospective observational study to determine the relationship between exposure to hyperglycemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes who were participants in the UKPDS. 3,642 white, Asian Indian and Afro-Caribbean UKPDS patients who had HbA1c measured 3 months after their diabetes diagnosis and with complete data for potential confounders were included in the sub-analysis of relative risk. Reductions in the risk of microvascular and macrovascular complications that might be achieved by lowering HbA1c by 1% were estimated. The incidence of clinical complications was found to be significantly associated with hyperglycemia. While any reduction in HbA1c is likely to reduce the risk of complications, the lowest risk was observed in those with HbA1c values in the normal range (< 6.0%). A 1% decrease in HbA1c was estimated to correspond with significant reductions in any diabetes-related endpoint, diabetes-related death, all cause mortality, myocardial infarction, stroke, peripheral vascular disease, microvascular disease and cataract extraction. Stratton IM, et al. UKPDS 35. BMJ 2000; 321:405 412.B         ^   :           a            O         ~   X H  0޽h ? ̙33 0 ,(  ^ S 9   g  c $ kg  pr  g  " H  0޽h ? ̙33  0   Z (  ^ S 9   g   c $`g  pr  g  P UKPDS showed that as type 2 diabetes progresses, monotherapy with traditional agents fails to maintain glycemic control. Of 1,704 overweight (>120% ideal bodyweight) patients with newly-diagnosed type 2 diabetes recruited to the study, 753 were included in a randomised trial of conventional therapy (diet alone, n = 411) versus intensive blood glucose control with metformin. A secondary analysis comparing the 342 patients allocated metformin with 951 overweight patients allocated intensive blood-gluose control with chlorpropamide (n = 256), glibenclamide (n = 277), or insulin (n = 409) found that over 10 years, median HbA1c was 7.4% in the metfromin group, compared with 8.0% in the conventional group. The patients assigned intensive control with sulfonylurea or insulin had similar HbA1c to the metformin group. UK Prospective Diabetes Study Group. UKPDS 34. Lancet 1998; 352:854 865. 5Lt        1       B1   +       `   <   8         X   4 .   $   V H  0޽h ? ̙33 0 @8 (  ^ S 9   g 2 c $g  pr  g   The UKPDS indicated an inevitable progression to combination therapy in the long term. After 3 years of intensive treatment with sulfonylurea or metformin monotherapy, approximately 50% of patients maintained HbA1c < 7%, whilst < 40% achieved this goal on intensive insulin therapy. After 9 years, this figure had fallen to approximately 25% with sulfonylurea and insulin and < 20% with insulin. Turner RC, et al. UKPDS 49. JAMA 1999; 281:2005 2012.            r        ' 5  H  0޽h ? ̙33t 0 4,0(  ^ S 9   g & c $g  pr  g  In the UKPDS, long-term increases in fasting plasma glucose were accompanied by progressive b-cell dysfunction. Mean b-cell function was already less than 50% at diagnosis,1 and none of the therapies used in the study (sulfonylureas, metformin and insulin) were able to prevent or delay the progressive deterioration of b-cell function.2 On average, b-cell function declines by 1% per year with normal ageing, compared with 4% per year in diabetes. 1. Holman RR. Diabetes Res Clin Pract 1998; 40 (Suppl.):S21 S25. 2. UK Prospective Diabetes Study Group. UKPDS 16. Diabetes 1995; 44:1249 1258.S\    6       c     D                       "      H  0޽h ? ̙33  0 p(  ^ S 9   g  c $g  pr  g  fRThe Diabetes in Canada Evaluation (DICE) Study revealed that the mean A1C for patients with type 2 diabetes was 0.073. When Canadian Diabetes Association CPG categories of glycemic control (A1C) were applied, 49.8% were ideal/optimal (<0.07); 32.1% were suboptimal (0.07-0.084) and 18.1% were inadequate (>0.084). The US National Health and Examination Survey (NHANES), conducted between 1988 and 1994, revealed that only 38% of the individuals with type 2 diabetes being treated with an oral anti-diabetic drug had acceptable glycemic control, according to current ADA guidelines.2 1. Harris S, et al. ADA 2003 - 2162-PO 2. Harris MI, et al. Diabetes Care 1999; 22:403 408.M]J    6     p  J      1 ] H  0޽h ? ̙33 0 5(  ^ S 9   g  c $(g  pr  g  +  H  0޽h ? ̙33  0    (  ^ S 9   g   c $$h  pr  g   Different anti-diabetic agents target distinct sites as part of their primary mechanism of action in reducing hyperglycemia. Sulfonylureas (e.g. glyburide) and meglitinides (e.g. repaglinide) stimulate insulin release from the pancreas. Biguanides (e.g. metformin) primarily suppress hepatic glucose output. a-glucosidase inhibitors (e.g. acarbose) delay digestion and absorption of carbohydrates in the gastrointestinal tract. Thiazolidinediones (e.g. rosiglitazone) decrease insulin resistance in adipose tissue, skeletal muscle and liver. In addition, these agents may have a beneficial effect on b-cell function. 1. Kobayashi M. Diabetes Obes Metab 1999; 1 (Suppl. 1):S32 S40. 2. Nattrass M & Bailey CJ. Baillieres Best Pract Res Clin Endocrinol Metab 1999; 13:309 329.}}   $        0 /    n                         /          /           N                           H  0޽h ? ̙33# 0 @,(  ^ S 9   h  c $ h  pr  h  " H  0޽h ? ̙33$ 0 ,(  ^ S 9   h  c $p.h  pr  h  " H  0޽h ? ̙33 % 0 N F @ (  ^ S 9   h @  c $/h  pr  h  x Stepwise approach The traditional stepwise approach aims primarily to control acute symptoms. Dietary measures and exercise are not usually sufficient to control glycemia beyond the first year of therapy. If oral monotherapy proves inadequate, combination therapy is usually started. If this also proves unsuccessful, conversion to insulin is the next step, either alone or in combination with an oral agent. In the majority of cases, the stepwise approach does not lead to sustained control. Many physicians intensify treatment only when symptoms of poor glycemic control become apparent, rather than when glycemic targets are not reached. Early, aggressive approach This approach to type 2 diabetes management avoids the risk of early treatment failure by adopting an intensive therapeutic strategy immediately upon diagnosis. Combinations of agents with complementary modes of action targeting the dual defects underlying type 2 diabetes (insulin resistance and b-cell dysfunction) are most likely to support tight, long-term glycemic control. Furthermore, combination therapy should be considered earlier in the regimen to provide additional glycemic control. Campbell IW. Br J Cardiol 2000; 7:625 631. j         ,   L  +    m      H  0޽h ? ̙33l6 0 ,$`(  X  C d   h $  S Wh d @  h  **Treatment goals and strategies must be tailored to the patient, with consideration given to individual risk factors. Glycemic targets for children 12 years of age and pregnant women differ from these targets. Please refer to  Other Relevant Guidelines for further details. **An A1C of 7.0% corresponds to a laboratory value of 0.070. Where possible, Canadian laboratories should standardize their A1C values to DCCT levels (reference range: 0.040 to 0.060). However, as many laboratories continue to use a different reference range, the target A1C value should be adjusted based on the specific reference range used by the laboratory that performed the test. As a useful guide: an A1C target of 7.0% refers to a threshold that is approximately 15% above the upper limit of normal. Xv + #    H  0޽h ? ̙337 0 ,(  ^  S d9   h   c $tmh d pr  h  " H  0޽h ? ̙33; 0 ,(  ^  S d9   h   c $h d pr  h  " H  0޽h ? ̙33> 0 `,(  ^  S d9   h   c $hth d pr  h  " H  0޽h ? ̙33/ 0 |( hvr R  3 d   h   C yh d @  h  " H  0޽h ? ̙33. 0 |(  R  3 d   h   C h d @  h  " H  0޽h ? ̙33 0 }u (  R  3 d   h {  C h d @T  h <4___PPT9  1. In people with type 2 diabetes, if glycemic targets are not achieved using lifestyle management within 2 to 3 months, antihyperglycemic agents should be initiated [Grade A, Level 1A] In the presence of marked hyperglycemia (A1C > 9.0%), antihyperglycemic agents should be initiated concomitant with lifestyle counselling.[Grade D, Consensus]. 2. If glycemic targets are not attained when a single antihyperglycemic agent is used initially, an antihyperglycemic agent or agents from other classed should be added. The lag period before adding other agent(s) should be kept to a minimum, taking into the account the pharmacokinetics of the different agents. Timely adjustments to and/or additions of antihyperglycemic agents should be made in order to attain target A1C within 6 to 12 months [Grade D, Consensus] 3. The choice of antihyperglycemic agent(s) should take into account the individual and the following factors: Unless contraindicated, a biguanide (metformin) should be the primary drug used in overweight patients [Grade A, level 1A]; and Other classes of antihyperglycemic agents may be used either alone or in combination to attain glycemic targets with consideration given to the information in Table 1 and Figure 1 [Grade D, Consensus for the order of antihyperglycemic agents listed in Figure 1] 4. In people with type 2 diabetes, if individual treatment goals have not been reached with a regimen of nutrition therapy, physical activity and a sulfonylurea [Grade 1, Level 1A], sulfonylurea plus metformin [Grade A, Level 1A] or other oral antihyperglycemic agents [Grade D, Consensus], insulin therapy should be initiated to improve glycemic control 5. Combining insulin and the following oral antihyperglycemic agents (listed in alphabetical order) has been shown to be effective in people with type 2 diabetes: alpha-glucosidase inhibitors (acarbose) [Grade A, Level 1A] biguanide (metformin) [Grade A, Level 1A] Insulin secretagogues (sulfonylureas) [Grade A, Level 1A] Insulin sensitizers (thiazolidinediones) [Grade A, Level 1A]. (The combination of an insulin sensitizer plus insulin is currently not an approved indication in Canada.) 6. Insulin may be used as initial therapy in type 2 diabetes [Grade A, Level 1A], especially in cases of marked hyperglycemia (A1C> 9.0%) [Grade D, Consensus] [1Z(Z(pZZ1(d1Z1(1ZIZ1F1ZZ             S  F &    '    %  (  j      '  K  J     a  (      s  g      d  =  r     #  M  7  l                  +     #  H  0޽h ? ̙337 0  ( |@|@  R   3 d   h    c $i 0e0e d @T  h <4___PPT9  1. In people with type 2 diabetes, if glycemic targets are not achieved using lifestyle management within 2 to 3 months, antihyperglycemic agents should be initiated [Grade A, Level 1A] In the presence of marked hyperglycemia (A1C > 9.0%), antihyperglycemic agents should be initiated concomitant with lifestyle counselling.[Grade D, Consensus]. 2. If glycemic targets are not attained when a single antihyperglycemic agent is used initially, an antihyperglycemic agent or agents from other classed should be added. The lag period before adding other agent(s) should be kept to a minimum, taking into the account the pharmacokinetics of the different agents. Timely adjustments to and/or additions of antihyperglycemic agents should be made in order to attain target A1C within 6 to 12 months [Grade D, Consensus] 3. The choice of antihyperglycemic agent(s) should take into account the individual and the following factors: Unless contraindicated, a biguanide (metformin) should be the primary drug used in overweight patients [Grade A, level 1A]; and Other classes of antihyperglycemic agents may be used either alone or in combination to attain glycemic targets with consideration given to the information in Table 1 and Figure 1 [Grade D, Consensus for the order of antihyperglycemic agents listed in Figure 1] 4. In people with type 2 diabetes, if individual treatment goals have not been reached with a regimen of nutrition therapy, physical activity and a sulfonylurea [Grade 1, Level 1A], sulfonylurea plus metformin [Grade A, Level 1A] or other oral antihyperglycemic agents [Grade D, Consensus], insulin therapy should be initiated to improve glycemic control 5. Combining insulin and the following oral antihyperglycemic agents (listed in alphabetical order) has been shown to be effective in people with type 2 diabetes: alpha-glucosidase inhibitors (acarbose) [Grade A, Level 1A] biguanide (metformin) [Grade A, Level 1A] Insulin secretagogues (sulfonylureas) [Grade A, Level 1A] Insulin sensitizers (thiazolidinediones) [Grade A, Level 1A]. (The combination of an insulin sensitizer plus insulin is currently not an approved indication in Canada.) 6. Insulin may be used as initial therapy in type 2 diabetes [Grade A, Level 1A], especially in cases of marked hyperglycemia (A1C> 9.0%) [Grade D, Consensus] [1Z(Z(pZZ1(d1Z1(1ZIZ1F1ZZ             S  F &    '    %  (  j      '  K  J     a  (      s    _      d  =  r     #  M  7  l                  +     $ H   0޽h ? ̙336  0 ( @ X@ R  3 d   i   c Wi 0e0e d @T  i <4___PPT9  1. In people with type 2 diabetes, if glycemic targets are not achieved using lifestyle management within 2 to 3 months, antihyperglycemic agents should be initiated [Grade A, Level 1A] In the presence of marked hyperglycemia (A1C > 9.0%), antihyperglycemic agents should be initiated concomitant with lifestyle counselling.[Grade D, Consensus]. 2. If glycemic targets are not attained when a single antihyperglycemic agent is used initially, an antihyperglycemic agent or agents from other classed should be added. The lag period before adding other agent(s) should be kept to a minimum, taking into the account the pharmacokinetics of the different agents. Timely adjustments to and/or additions of antihyperglycemic agents should be made in order to attain target A1C within 6 to 12 months [Grade D, Consensus] 3. The choice of antihyperglycemic agent(s) should take into account the individual and the following factors: Unless contraindicated, a biguanide (metformin) should be the primary drug used in overweight patients [Grade A, level 1A]; and Other classes of antihyperglycemic agents may be used either alone or in combination to attain glycemic targets with consideration given to the information in Table 1 and Figure 1 [Grade D, Consensus for the order of antihyperglycemic agents listed in Figure 1] 4. In people with type 2 diabetes, if individual treatment goals have not been reached with a regimen of nutrition therapy, physical activity and a sulfonylurea [Grade 1, Level 1A], sulfonylurea plus metformin [Grade A, Level 1A] or other oral antihyperglycemic agents [Grade D, Consensus], insulin therapy should be initiated to improve glycemic control 5. Combining insulin and the following oral antihyperglycemic agents (listed in alphabetical order) has been shown to be effective in people with type 2 diabetes: alpha-glucosidase inhibitors (acarbose) [Grade A, Level 1A] biguanide (metformin) [Grade A, Level 1A] Insulin secretagogues (sulfonylureas) [Grade A, Level 1A] Insulin sensitizers (thiazolidinediones) [Grade A, Level 1A]. (The combination of an insulin sensitizer plus insulin is currently not an approved indication in Canada.) 6. Insulin may be used as initial therapy in type 2 diabetes [Grade A, Level 1A], especially in cases of marked hyperglycemia (A1C> 9.0%) [Grade D, Consensus] [1Z(Z(pZZ1(d1Z1(1ZIZ1F1ZZ             S  F &    '    %  (  j      '  K  J     a  (      s    _      d  =  r     #  M  7  l                  +     # H  0޽h ? ̙336 0 ( @ X@ R  3 d   i   c j 0e0e d @T  i <4___PPT9  1. In people with type 2 diabetes, if glycemic targets are not achieved using lifestyle management within 2 to 3 months, antihyperglycemic agents should be initiated [Grade A, Level 1A] In the presence of marked hyperglycemia (A1C > 9.0%), antihyperglycemic agents should be initiated concomitant with lifestyle counselling.[Grade D, Consensus]. 2. If glycemic targets are not attained when a single antihyperglycemic agent is used initially, an antihyperglycemic agent or agents from other classed should be added. The lag period before adding other agent(s) should be kept to a minimum, taking into the account the pharmacokinetics of the different agents. Timely adjustments to and/or additions of antihyperglycemic agents should be made in order to attain target A1C within 6 to 12 months [Grade D, Consensus] 3. The choice of antihyperglycemic agent(s) should take into account the individual and the following factors: Unless contraindicated, a biguanide (metformin) should be the primary drug used in overweight patients [Grade A, level 1A]; and Other classes of antihyperglycemic agents may be used either alone or in combination to attain glycemic targets with consideration given to the information in Table 1 and Figure 1 [Grade D, Consensus for the order of antihyperglycemic agents listed in Figure 1] 4. In people with type 2 diabetes, if individual treatment goals have not been reached with a regimen of nutrition therapy, physical activity and a sulfonylurea [Grade 1, Level 1A], sulfonylurea plus metformin [Grade A, Level 1A] or other oral antihyperglycemic agents [Grade D, Consensus], insulin therapy should be initiated to improve glycemic control 5. Combining insulin and the following oral antihyperglycemic agents (listed in alphabetical order) has been shown to be effective in people with type 2 diabetes: alpha-glucosidase inhibitors (acarbose) [Grade A, Level 1A] biguanide (metformin) [Grade A, Level 1A] Insulin secretagogues (sulfonylureas) [Grade A, Level 1A] Insulin sensitizers (thiazolidinediones) [Grade A, Level 1A]. (The combination of an insulin sensitizer plus insulin is currently not an approved indication in Canada.) 6. Insulin may be used as initial therapy in type 2 diabetes [Grade A, Level 1A], especially in cases of marked hyperglycemia (A1C> 9.0%) [Grade D, Consensus] [1Z(Z(pZZ1(d1Z1(1ZIZ1F1ZZ             S  F &    '    %  (  j      '  K  J     a  (      s    _      d  =  r     #  M  7  l                  +     # H  0޽h ? ̙33B 0 |`(  R  3 d   j   C Lj d @  j  " H  0޽h ? ̙33D 0 (( FWFW (R ( 3 d   j  ( C cj d @T  j <4___PPT9  1. In people with type 2 diabetes, if glycemic targets are not achieved using lifestyle management within 2 to 3 months, antihyperglycemic agents should be initiated [Grade A, Level 1A] In the presence of marked hyperglycemia (A1C > 9.0%), antihyperglycemic agents should be initiated concomitant with lifestyle counselling.[Grade D, Consensus]. 2. If glycemic targets are not attained when a single antihyperglycemic agent is used initially, an antihyperglycemic agent or agents from other classed should be added. The lag period before adding other agent(s) should be kept to a minimum, taking into the account the pharmacokinetics of the different agents. Timely adjustments to and/or additions of antihyperglycemic agents should be made in order to attain target A1C within 6 to 12 months [Grade D, Consensus] 3. The choice of antihyperglycemic agent(s) should take into account the individual and the following factors: Unless contraindicated, a biguanide (metformin) should be the primary drug used in overweight patients [Grade A, level 1A]; and Other classes of antihyperglycemic agents may be used either alone or in combination to attain glycemic targets with consideration given to the information in Table 1 and Figure 1 [Grade D, Consensus for the order of antihyperglycemic agents listed in Figure 1] 4. In people with type 2 diabetes, if individual treatment goals have not been reached with a regimen of nutrition therapy, physical activity and a sulfonylurea [Grade 1, Level 1A], sulfonylurea plus metformin [Grade A, Level 1A] or other oral antihyperglycemic agents [Grade D, Consensus], insulin therapy should be initiated to improve glycemic control 5. Combining insulin and the following oral antihyperglycemic agents (listed in alphabetical order) has been shown to be effective in people with type 2 diabetes: alpha-glucosidase inhibitors (acarbose) [Grade A, Level 1A] biguanide (metformin) [Grade A, Level 1A] Insulin secretagogues (sulfonylureas) [Grade A, Level 1A] Insulin sensitizers (thiazolidinediones) [Grade A, Level 1A]. (The combination of an insulin sensitizer plus insulin is currently not an approved indication in Canada.) 6. Insulin may be used as initial therapy in type 2 diabetes [Grade A, Level 1A], especially in cases of marked hyperglycemia (A1C> 9.0%) [Grade D, Consensus] [1Z(Z(pZZ1(d1Z1(1ZIZ1F1ZZ             S  F &    '    %  (  j      '  K  J     a  (      s    _      d  =  r     #  M  7  l                  +     # H ( 0޽h ? ̙336 0 p,( h ,R , 3 d   j  , c ̊j 0e0e d @T  j <4___PPT9  1. In people with type 2 diabetes, if glycemic targets are not achieved using lifestyle management within 2 to 3 months, antihyperglycemic agents should be initiated [Grade A, Level 1A] In the presence of marked hyperglycemia (A1C > 9.0%), antihyperglycemic agents should be initiated concomitant with lifestyle counselling.[Grade D, Consensus]. 2. If glycemic targets are not attained when a single antihyperglycemic agent is used initially, an antihyperglycemic agent or agents from other classed should be added. The lag period before adding other agent(s) should be kept to a minimum, taking into the account the pharmacokinetics of the different agents. Timely adjustments to and/or additions of antihyperglycemic agents should be made in order to attain target A1C within 6 to 12 months [Grade D, Consensus] 3. The choice of antihyperglycemic agent(s) should take into account the individual and the following factors: Unless contraindicated, a biguanide (metformin) should be the primary drug used in overweight patients [Grade A, level 1A]; and Other classes of antihyperglycemic agents may be used either alone or in combination to attain glycemic targets with consideration given to the information in Table 1 and Figure 1 [Grade D, Consensus for the order of antihyperglycemic agents listed in Figure 1] 4. In people with type 2 diabetes, if individual treatment goals have not been reached with a regimen of nutrition therapy, physical activity and a sulfonylurea [Grade 1, Level 1A], sulfonylurea plus metformin [Grade A, Level 1A] or other oral antihyperglycemic agents [Grade D, Consensus], insulin therapy should be initiated to improve glycemic control 5. Combining insulin and the following oral antihyperglycemic agents (listed in alphabetical order) has been shown to be effective in people with type 2 diabetes: alpha-glucosidase inhibitors (acarbose) [Grade A, Level 1A] biguanide (metformin) [Grade A, Level 1A] Insulin secretagogues (sulfonylureas) [Grade A, Level 1A] Insulin sensitizers (thiazolidinediones) [Grade A, Level 1A]. (The combination of an insulin sensitizer plus insulin is currently not an approved indication in Canada.) 6. Insulin may be used as initial therapy in type 2 diabetes [Grade A, Level 1A], especially in cases of marked hyperglycemia (A1C> 9.0%) [Grade D, Consensus] [1Z(Z(pZZ1(d1Z1(1ZIZ1F1ZZ             S  F &    '    %  (  j      '  K  J     a  (      s    _      d  =  r     #  M  7  l                  +     # H , 0޽h ? ̙331 0 |`4(  4R 4 3 d   j  4 C j d @  j  " H 4 0޽h ? ̙33T 0  (  X  C d   j   S |j d @  j  " H  0޽h ? ̙33U 0  (  X  C d   j   S j d @  j  " H  0޽h ? ̙33]V 0 p(  X  C d   N  S 5Nd @  N 1Can J Diabetes 2003; 27(Suppl 2):s 18-20, 37-41. B21  H  0޽h ? ̙33c 0 5(  ^  S d9   j   c $hj d pr  j  +  H  0޽h ? ̙33d 0 5(  ^  S d9   j   c $,kj d pr  j  +  H  0޽h ? ̙33Q 0 |( @ R  3 d   j   C hj d @  j  " H  0޽h ? ̙33R 0 |( \)  R  3 d   j   C j d @  j  " H  0޽h ? ̙33S 0 |( Y R  3 d   j   C j d @  j  " H  0޽h ? ̙33G 0 |( @ R  3 d   k   C k d @  k  " H  0޽h ? ̙33H 0 |( @ R  3 d   k   C T k d @  k  " H  0޽h ? ̙33I 0 |((  (R ( 3 d   k  ( C Kj d @  k  " H ( 0޽h ? ̙33J 0 | 4(  4R 4 3 d   k  4 C Lk d @  k  " H 4 0޽h ? ̙33K 0 |@@(  @R @ 3 d   k  @ C k d @  k  " H @ 0޽h ? ̙33L 0 |`L(  LR L 3 d   k  L C lk d @  k  " H L 0޽h ? ̙33M 0 |X(   XR X 3 d   k  X C |$k d @  k  " H X 0޽h ? ̙33N 0 |d(  dR d 3 d   k  d C *k d @  k  " H d 0޽h ? ̙33O 0 |p(  pR p 3 d   k  p C /k d @  k  " H p 0޽h ? ̙33W 0 ||( p |R | 3 d   k  | C (5k d @  k  " H | 0޽h ? ̙33X 0 | (  R  3 d   k   C :k d @  k  " H  0޽h ? ̙33Y 0 |@(   R  3 d   k   C ?k d @  k  " H  0޽h ? ̙33Z 0 |P(  R  3 d   k   C LEk d @  k  " H  0޽h ? ̙33[ 0 |p( (}@ R  3 d   k   C Jk d @  k  " H  0޽h ? ̙33\ 0 |(  R  3 d   k   C Pk d @  k  " H  0޽h ? ̙33] 0 |(  TH0 R  3 d   k   C TUk d @  k  " H  0޽h ? ̙33^ 0 |( 5% R  3 d   k   C Zk d @  k  " H  0޽h ? ̙33_ 0 |(  R  3 d   k   C t`k d @  k  " H  0޽h ? ̙33` 0 |(  R  3 d   k   C fk d @  k  " H  0޽h ? ̙33a 0 |0( *X}p R  3 d   k   C kk d @  k  " H  0޽h ? ̙33b 0 |P(  R  3 d   k   C  qk d @  k  " H  0޽h ? ̙33e 0  (  X  C d   k   S vk d @  k  " H  0޽h ? ̙33TPx\]lTE>sOv)"RM KRmP(e.[K IM4"QH|QIODQ|mL  ]ϙ۽{wݭԦd왿{ߝo6t_`H8LiL @H$b$GA1BmG1wP2P(L9b 4\(3Pf|ԳP@2e'ax>Jb(%c=/ >X;Q`u+y8c [:͝ 沽 ^pIRW@3@됍 ԜTS?~hiG'ZgT?Y&^18]~lܷ}:BධoS0Wl 9հ0/ epk]c't9)n4FKC(gcZ=ڦ3p@R}BGKH`Muab4ǜPweh܀59B#[#\룵9lvݮ/b.Y؉;F=-Pv4ۙƜ4@/}ls_A> KKLzCW=rvVIxSc.:Cť)oB88<gpxC:Z]Ѐ T_T'HQPPPPPPPPPP/!XG?)si=Q8C:'*c6imƒ*_5}򴻉[uGDD2@TsBx'Ύ5}{l+ y&3F؟%}|S9nff(eĴQl~bw=@N0li3Y2<[*=p 8H3CgкuG4\lOKv|_ Gxp2mC2M7RU8$ ax*+8bįV /Xf{&j_"Mvq!H=ָUĭϏẠ~[:߮d8Mʚ(_HP((,߾~ɮB\_QFXu4Sz5&AP4~93'K`~5Oʬh &2h42b_̴:y>З_PS2RH| //X9qFLv3&x `^c>.gʂ#b]?p]W<^uޏqA郧$^Kx~!|1mĘ|f^a/'ELgX 512ANlaq+:-ZJw\|56UTVVT7i0sl -e[a^߇Aɪq7_һR'ṭXRG5dh/\<\6.(]tD-i!Wz o6 ƒ qGģ| ~OYikz(0+fB5ԠPV#1=sMd]V8ܴnkFj]e\q Ce(TK1w1,2G0^bN9_I: ?rX0p= G A AZ  aQ`he:sR% w(*0L. 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%O =$V".Many patients have inadequate glycemic control//2       QRSTU&The evolution of management guidelines''" '  Studies including UKPDS have highlighted the importance of glycemic control in reducing complications New guidelines include tighter targets for glycemic control Guidelines recognize importance of treating all aspects of the condition Current guidelines therefore include targets for glycemic control lipid levels blood pressure^1 2> PowerPoint Document( DocumentSummaryInformation8;:?1*7,riKOQSUWY[+*FFGHF_%_DBc!CfB ClB'pCrCt]?A4&]&&46PR9VXZ\NAO@PQAR@RSAT@UVAW@X Hb$AoQ-+,ra%+52$Y:^X5ؤr9+52$u2Sxq8*&`n2$w$ia?d8ZZ2$p$r_)2$-bVs*kɱT2$]5J =a 5kpn3$$2$5Pq}vLyKuR${+DUQ聑Odv# lfAA5%"  f33333@pg4BdBd  0pp@p@ <42d2dLqt 0X{ <4BdBdLp 0g4dd  0p@ ppFlO ʚ;38ʚ;<4ddddL@v 08~0___PPT10 >___PPT9 0$ ; y 2  3 2*3 ZD  P    3 \UKPDS: decreased risk of diabetes-related complications associated with a 1% decrease in A1C,]\ ] :UKPDS: the benefits of improved glycemic control;;$&*     Improved glycemic control significantly reduces risk of diabetes-related complications UKPDS results indicated that a 1% reduction in A1C would reduce the risk of microvascular complications by 37%, but have less effect (16%) on macrovascular complications Further improvement in sustained glycemic control and reduction in the burden of cardiovascular disease are needed70Z2&0Z 50Z20Z 40Z2I0Z t      C   2  R CUKPDS demonstrated loss of glycemic control with all agents studiedDD$2         IProportion of patients with A1C < 7.0% on monotherapy at 3, 6 and 9 yearsJZJ &*    !The UKPDS demonstrated progressive decline of b-cell function over timeNH.$$$$G   *#1998 CDA Treatment Targets$  V6O1 `7+$Lifestyle Intervention$   The first step in treating type 2 diabetes Nutrition therapy and exercise can improve glycemic control Success of lifestyle intervention related to: patient s initial fasting plasma glucose level amount of weight loss achieved by patient Only a minority of patients are able to attain treatment targets using lifestyle intervention alone. T-ZZ>sZZ0sZ]Z sZ=sZ1sZZm0]p&[    d;EUKPDS 7: Response of FPG to Diet Therapy in Newly Diagnosed PatientsFF$E   N= 3044, newly diagnosed patients FPG at diagnosis 12.1+/- 3.7 mmol/L Diet counseling Patients with FPG 10-12 mmol/L needed reduction of 28% ideal body weight; to attain FPG <6 mmol/L 16% achieved FPG <6 after 3 months: in the group presenting with FPGs of 6-8 mmol/L 50% met this target in the group presenting with FPGs of 16-22 mmol/L only 10% were successfulsZ/0 sZ &sZ6ZZ0 sZ 4ZZ0 sZ &D  /  D  G    9       %  &9Primary Sites of Action of Oral Antihyperglycemic Agents::$&!   |DKey Recommendations   VAntihyperglycemic agents should be initiated if glycemic targets not met after 2-3 months of lifestyle intervention Antihyperglycemic agents should be started concomitantly with lifestyle if A1C levels are greater than 9% The lag period before adding other agent(s) should be kept to a minimum to achieve glycemic targets within 6-12 months Unless contraindicated, metformin should be used first line; other agents should be considered in the order they appear in the treatment algorithm Insulin therapy should be initiated if targets cannot be achieved with lifestyle changes and oral therapy 0Vl ZZW   =    5    ,%*New Treatment Options for Type 2 Diabetes++$*   i>/Management of Hyperglycemia in Type 2 Diabetes00$&     DZ   M.N/ rB A1C <7% (< 6% if can be achieved safely) Aim to achieve targets within 6-12 months Start with combination therapy or insulin for patients with A1C > 9% Consider insulin at any stage of treatment Vascular protection to further reduce cardiovascular risk)l *l El +l :l k  ed  GHIJKLMNOc  WXYZ[\]^_`ab/<./23456 7 : ;?@A]a"f$k&s*t+u,v-w.x/y0~23589:;<=>?@ABCDEFGHIJKLMNOPQRSTUrd V? jd ;(    *Document Word.Document.80.Microsoft Word Document/ 0DTimes New Roman 0 0DArialNew Roman 0 0 DGeorgiawcrosoft Word DocumentSlide 1/Many patients have inadequate glycemic controlSlide 3Slide 4Slide 5Slide 6Slide 7'The evolution of management guidelines]UKPDS: decreased risk of diabetes-related complications associated with a 1% decrease in A1C;UKPDS: the benefits of improved glycemic controlDUKPDS demonstrated loss of glycemic control with all agents studiedJProportion of patients with A1C < 7.0% on monotherapy at 3, 6 and 9 yearsJThe UKPDS demonstrated progressive decline of -cell function over time Slide 141998 CDA Treatment Targets Slide 16 Slide 17 Slide 18Lifestyle InterventionFUKPDS 7: Response of FPG to Diet Therapy in Newly Diagnosed Patients Slide 21:Primary Sites of Action of Oral Antihyperglycemic AgentsKey Recommendations+New Treatment Options for Type 2 Diabetes0Management of Hyperglycemia in Type 2 Diabetes Slide 26 Slide 27 Slide 28 Slide 29 Slide 30 Slide 31 Slide 32 Slide 33 Slide 34 Slide 35 Slide 36 Slide 37 Slide 38 Slide 39 Slide 40 Slide 41 Slide 42 Slide 43 Slide 44 Slide 45 Slide 46 Slide 47 Slide 48 Slide 49 Slide 50 Slide 51 Slide 52 Slide 53 Slide 54 Slide 55 Slide 56 Slide 57  Fonts UsedDesign TemplateEmbedded OLE Servers Slide Titles90>? %O ="V".Many patients have inadequate glycemic control//.   QRSTU&The evolution of management guidelines''" '  Studies including UKPDS have highlighted the importance of glycemic control in reducing complications New guidelines include tighter targets for glycemic control Guidelines recognize importance of treating all aspects of the condition Current guidelines therefore include targets for glycemic control lipid levels blood pressure^1 2>  y 2  3 2*3  s \UKPDS: decreased risk of diabetes-related complications associated with a 1% decrease in A1C,]\ ] :UKPDS: the benefits of improved glycemic control;;$ ;  Improved glycemic control significantly reduces risk of diabetes-related complications UKPDS results indicated that a 1% reduction in A1C would reduce the risk of microvascular complications by 37%, but have less effect (16%) on macrovascular complications Further improvement in sustained glycemic control and reduction in the burden of cardiovascular disease are needed70Z2&0Z 50Z20Z 40Z2I0Z &    CUKPDS demonstrated loss of glycemic control with all agents studiedDD$C    IProportion of patients with A1C < 7.0% on monotherapy at 3, 6 and 9 yearsJZJ  J !The UKPDS demonstrated progressive decline of b-cell function over timeNH.$$$$G   *#1998 CDA Treatment Targets$  V6O1 `7+$Lifestyle Intervention$   The first step in treating type 2 diabetes Nutrition therapy and exercise can improve glycemic control Success of lifestyle intervention related to: patient s initial fasting plasma glucose level amount of weight loss achieved by patient Only a minority of patients are able to attain treatment targets using lifestyle intervention alone. T-ZZ>sZZ0sZ]Z sZ=sZ1sZZm0]p m d;EUKPDS 7: Response of FPG to Diet Therapy in Newly Diagnosed PatientsFF$E   N= 3044, newly diagnosed patients FPG at diagnosis 12.1+/- 3.7 mmol/L Diet counseling Patients with FPG 10-12 mmol/L needed reduction of 28% ideal body weight; to attain FPG <6 mmol/L 16% achieved FPG <6 after 3 months: in the group presenting with FPGs of 6-8 mmol/L 50% met this target in the group presenting with FPGs of 16-22 mmol/L only 10% were successfulsZ/0 sZ &sZ6ZZ0 sZ 4ZZ0 sZ &L   E  -  %  &9Primary Sites of Action of Oral Antihyperglycemic Agents::$&!   |DKey Recommendations   VAntihyperglycemic agents should be initiated if glycemic targets not met after 2-3 months of lifestyle intervention Antihyperglycemic agents should be started concomitantly with lifestyle if A1C levels are greater than 9% The lag period before adding other agent(s) should be kept to a minimum to achieve glycemic targets within 6-12 months Unless contraindicated, metformin should be used first line; other agents should be considered in the order they appear in the treatment algorithm Insulin therapy should be initiated if targets cannot be achieved with lifestyle changes and oral therapy 0Vl ZZWN d      ,%*New Treatment Options for Type 2 Diabetes++$*   i>/Management of Hyperglycemia in Type 2 Diabetes00$&     DZ   M.N/ rB A1C <7% (< 6% if can be achieved safely) Aim to achieve targets within 6-12 months Start with combination therapy or insulin for patients with A1C > 9% Consider insulin at any stage of treatment Vascular protection to further reduce cardiovascular risk)l *l El +l :l k  ed  GHIJKLMNOc  WXYZ[\]^_`ab/<./23456 7 : ;?@A]a"f$k&s*t+u,v-w.x/y0~23589:;<=>?@ABCDEFGHIJKLMNOPQRSTUr2 b  W