Initiating Insulin Therapy in Type 2 Diabetes

1

• Initiating Insulin Therapy in Type 2 Diabetes
• DIABETES CARE, Feb. 2005
• Raskin Philip for the
• INITIATE study group

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The INITIATE study NovoMix 30 (BID) vs
glargine (OD)
n 233 Type 2 DM BMI lt 40 kg/m2Body weight lt125
kg (275 lbs) HbA1C gt 8 on metformin /- TZD
Glargine OD (12 U, bedtime) metformin /-
pioglitazone
NovoMix 30, pre-breakfast (6U) and pre-dinner
(6U) metformin /- pioglitazone
4 wk run-in Stop insulin secretagogues (SUs,
nateglinide, repaglinide) and ?-glucosidase
inhibitors (acarbose) Optimize metformin to 1500
mg/day Switch rosiglitazone (Avandia) for 30 mg
pioglitazone (Actos)

-4 0 28 (Weeks)
INITIATE Raskin et al Diabetes, June 2004, vol
53, suppl. 2, p. A143
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Study endpoints for INITIATE

• Primary Compare HbA1c reduction
• Secondary
• Endpoint HbA1C values including the proportion of
  patients achieving HbA1C lt 7,0 and lt6,5
• 8-point BG profile showing fasting plasma glucose
  and postprandial glucose
• Safety, including number of hypoglycaemic events
  (major, minor and nocturnal) and adverse events
• Treatment satisfaction as determined by the
  Diabetic Treatment Satisfaction Questionnaire
  (DTSQ) and Insulin Treatment Satisfaction
  Questionnaire (ITSQ)
• Insulin dose and weight change

INITIATE Raskin et al Diabetes, June 2004, vol
53, suppl. 2, p. A143
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Treat-to-targetInitiation and titration

• Starting doses
• NovoMix 30 in FlexPen Glargine in
  vial
• 12U (6U at breakfast, 6U at dinner) 12U at
  bedtime
• If FPG lt180 mg/dl or 10 mmol/l10U (5U 5U for
  NovoMix 30)
• Titration occurred weekly during the first 12
  weeks, then every 2 weeks thereafter
• Titration of dinnertime NovoMix 30 and bedtime
  glargine based on fasting blood glucose (80110
  mg/dl, 4.46.1 mmol/l) over previous 3 days
  breakfast NovoMix 30 titrated based on
  pre-dinner blood glucose over previous 3 days

INITIATE Raskin et al Diabetes, June 2004, vol
53, suppl. 2, p. A143
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Treat to Target with forced titration
FBG or pre-dinner SMBG (mg/dL) (mmol/l) FBG or pre-dinner SMBG (mg/dL) (mmol/l) NovoMix 30 dose adjustment Glarginedose adjustment
lt 80 lt 4.4 -2 U -2 U
80?110 4.4?6.1 - -
111?140 6.2?7.8 2 U 2?4 U
141?180 7.83?10 4 U 4?6 U
gt 180 gt 10 6 U 6?8 U
INITIATE Raskin et al Diabetes, June 2004, vol
53, suppl. 2, p. A143
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Baseline demographics
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?????? ?????? ???? ?? ???????? 30 ??? ????? ?????
?? ?? ????? ????? ??????? ???? ?????? ???? ?????
????? ?-25 ??????? ???????
2 am
Bedtime
Lunch 90
Dinner 90
Before lunch
Before dinner
Breakfast 90
Before breakfast
INITIATE Raskin et al Diabetes Care, Vol. 28, No.
2, February 2005
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???????? 30 ??? ????? ????? ?- HbA1c ???????
???? ?? ?? ????? ????? ?????? ???? ?????
???????? ???? ?????? ????? HbA1cgt8.5 - ???????
???????
NovoMix 30 (n 100) Glargine (n 109) p-value
Baseline HbA1C Week 28 HbA1C Reduction in FPG (change from baseline for all pt.) Reduction in FPG (change from baseline for pt. HbA1cgt8.5) 9.70 ?1.48 6.91 ?1.1 -2.79 ?0.11 -3.13 ?1.63 9.84 ?1.42 7.41 ?1.3 -2.36 ?0.11 -2.60 ?1.50 0.4782 lt0.01 lt0.01 lt 0.05

INITIATE Raskin et al Diabetes Care, Vol. 28, No.
2, February 2005
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HbA1c ???????? 30 ??? ????? ????? ??????
ADA ????????? ????? ????? ????? ?? 66 ???????
?- 40 ??????? ??????
INITIATE Raskin et al Diabetes Care, Vol. 28, No.
2, February 2005
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INITIATE - Hypoglycemia

• One major hypoglycaemic episode reported during
  the trial this was in the glargine group
• At least one episode of minor hypoglycaemia
  (BGlt56mg/dl or 3.1 mmol/L) was experienced in 43
  of NovoMix 30-treated patients and 16 of
  glargine-treated patients
• For patients having minor hypoglycaemic episodes,
  the median rate of minor hypoglycaemia per
  patient per month was similar between groups (0.3
  and 0.2 episodes per patient month for NovoMix
  30 and glargine, respectively p0.54)
• Similar treatment satisfaction (details on next
  slide)

INITIATE Raskin et al Diabetes, June 2004, vol
53, suppl. 2, p. A143