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Insulin detemir: weight neutral

Insulin detemir: weight neutral . Hans Häring Germany. Agenda. The problem of weight gain in insulin-treated diabetes Effect of insulin detemir on weight Possible mechanisms explaining differential insulin detemir and NPH insulin weight outcomes . Weight gain in type 1 diabetes in the DCCT.

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Insulin detemir: weight neutral

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  1. Insulin detemir: weight neutral Hans Häring Germany

  2. Agenda • The problem of weight gain in insulin-treated diabetes • Effect of insulin detemir on weight • Possible mechanisms explaining differential insulin detemir and NPH insulin weight outcomes

  3. Weight gain in type 1 diabetes in the DCCT Intensive therapy Conventional therapy p < 0.0001 6 30 5 20 4 Change in mean weight (kg) Change in weight (kg) 3 10 2 0 1 0 – 10 1st 2nd 3rd 4th n = 146 n = 131 Weight gain (quartiles) at mean follow up of 6.1 years Initial 12 months DCCT. Diabetes Care 1988;11:567-73 and Purnell et al. JAMA 1998;280:140-46

  4. * p < 0.01 compared with baseline and first quartile at follow up Cardiovascular risk factors increase with weight gain in type 1 diabetes (DCCT) Total cholesterol SystolicBP DiastolicBP HDL LDL 8 * * 6 * * 4 2 Percent change from baseline 0 –2 Gained the most weight(fourth quartile of weight gain) –4 * –6 Gained the least weight(first quartile of weight gain) –8 –10 Patients on intensive insulin therapy – changes from baseline to follow up (mean 6.1 years) Purnell et al. JAMA 1998;280(2):140-6.

  5. In the UKPDS, insulin-treated patients with type 2 diabetes gained the most weight 10 insulin conventional 7.5 chlorpropamide glibenclamide 5 Change in weight (kg) metformin 2.5 0 0 3 6 9 12 Years from randomisation –2.5 While patients on all therapies gained weight, patients receiving insulin gained the most UKPDS 34. Lancet 1998:352:854–865.

  6. Cardiovascular risk factors and weight in patients with type 2 diabetes • Possible multiple CV risk factors at time of diagnosis of type 2 diabetes • Bodyweight and CV risk are associated1 • Losing weight improves CV risk profiles2 • In a study of 100 people with type 2 diabetes treated with insulin or insulin/OAD therapy, all gained weight3 • Systolic BP and LDL cholesterol levels increased • Weak but positive relationship between systolic BP and weight gain (r=0.22) 1. Anderson JW, Kendall CW, Jenkins DJ. J Am Coll Nutr 2003;22(5):331-9. 2. Markovic TP et al. Diabetes Care 1998;21(5):695-700. 3. Yki-Jarvinen H et al. J Clin Endocrinol Metab 1997;82(12):4037-43.

  7. Why do people on insulin gain weight? • Better glycaemic control –  glycosuria1 • Anabolic effects of insulin –  fat storage2 • Decreased basal metabolic rate – less energy expenditure1 • Defensive eating against hypoglycaemia 1. Carlson et al. Diabetes 1993;42:1700-1707 2. Birkeland et al. J Intern Med 1994;236:305-13

  8. Effect of insulin detemir on weight1. Long-term study • 12-month comparison. Basal-bolus insulin aspart plus NPH insulin or insulin detemir • Patients with type 1 diabetes, n = 315 De Leeuw et al. (in press 2004)

  9. Change in weight with insulin detemir vs. NPH insulin in patients with type 1 diabetes p < 0.001 (12 months) 1.2 Insulin detemir NPH insulin 0.6 Change in weight (kg) 0 –0.6 3 6 9 12 Months De Leeuw et al. (in press 2004)

  10. Effect of insulin detemir on weight2. Children and adolescents • 6-month comparison. Basal-bolus insulin aspart plus NPH insulin or insulin detemir • Patients aged 6-17 with type 1 diabetes, n = 347 De Leeuw et al. (in press 2004)

  11. 0.8 0.7 p < 0.001 0.6 0.5 0.4 Change in BMI (kg/m2 ) 0.3 0.2 0.1 0 Weight and BMI, insulin detemir vs. NPH insulin, children & adolescents, type 1 diabetes 4.0 3.5 p < 0.001 3.0 2.5 2.0 Change in weight (kg) 1.5 1.0 0.5 0 NPH Insulin detemir Robertson et al. Diabetes 2004;53 (Suppl. 2):A144

  12. 0.8 0.7 p = 0.002 0.6 0.5 p = 0.004 0.4 Change in BMI (kg/m2 ) 0.3 0.2 0.1 0 6 – 11 12 – 17 Weight and BMI, insulin detemir vs. NPH insulin, children & adolescents, type 1 diabetes NPH 4.0 Insulindetemir 3.5 p = 0.003 3.0 p = 0.009 2.5 Change in weight (kg) 2.0 1.5 1.0 0.5 0 Age (yrs): 12 – 17 6 – 11 Robertson et al. Diabetes 2004;53 (Suppl. 2):A144

  13. Effect of insulin detemir on weight3. Type 2 diabetes treat-to-target trials • 24-week addition of basal insulin to OADs in insulin-naive patients with type 2 diabetes De Leeuw et al. (in press 2004)

  14. Insulin glargine vs. NPH insulinTreat-to-target trial: HbA1c and weight 9.0 3.5 NPH + OAD + 3.0 kg + 2.8 kg 3 Insulin glargine + OAD 8.5 2.5 8.0 Change in weight from baseline to endpoint (kg) 2 HbA1c (%) 7.5 1.5 7.0 1 6.5 0.5 0 0 4 8 12 16 20 24 Insulin glargine + OAD NPH + OAD Weeks Riddle et al. Diabetes Care 2003;26:3080-3086

  15. Insulin detemir vs. NPH insulinTreat-to-target trial: HbA1c and weight p < 0.05 9.0 3.5 Insulin detemir + OAD + 2.8 kg 3 NPH + OAD 8.5 2.5 8.0 Change in weight from baseline to endpoint (kg) 2 HbA1c (%) 7.5 + 1.2 kg 1.5 7.0 1 6.5 0.5 0 24 Insulin detemir+ OAD NPH + OAD 0 12 -2 Weeks Accepted at EASD 2004 as Poster 754:PS 64.

  16. Less weight gain with insulin detemir than NPH insulin – a rapid and sustained effect Insulin detemir NPH 86 85 p < 0.001 84 83 Weight (kg) 82 81 0 -2 1 3 5 7 9 11 13 15 17 19 21 23 Weeks Hermansen et at EASD 2004 Poster 754:PS 64.

  17. Effect of insulin detemir on weight4. Overview of phase III studies

  18. Weight change: insulin detemir phase III studies Insulin detemir *p<0.05, insulin detemir vs NPH 2 NPH insulin * * * * * * * * * * * 1.5 1 Weight change (kg) 0.5 0 type 2 diabetes -0.5 # † ‡ ## -1 Haak Home Vague Home Standl Pieber Pieber Rašlová De Leeuw Hermansen Russell-Jones †IDet (am+bed); ‡IDet (am+predinner); #IDet (12hourly); ##IDet (am+bed)

  19. Possible mechanisms for reduced weight gain with insulin detemir • Reduced snacking due to reduced risk of hypoglycaemia? • Increased ratio of hepatic:peripheral activity? • A CNS effect?

  20. Conclusion • Weight gain is associated with insulin treatment in people with type 1 and type 2 diabetes • The consequences of gaining weight or being overweight can be serious and are worrying in people with type 1 or type 2 diabetes • Treatment with insulin detemir results in good glycaemic control without weight gain

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