Insulin detemir reduces weight gain as a result of reduced food intake in patients with type 1 diabetes

Sunil Zachariah, Ben Sheldon, Fariba Shojaee-Moradie, Nicola C Jackson, Katharine Backhouse, Sigurd Johnsen, Richard H Jones, A Margot Umpleby, David L Russell-Jones, Sunil Zachariah, Ben Sheldon, Fariba Shojaee-Moradie, Nicola C Jackson, Katharine Backhouse, Sigurd Johnsen, Richard H Jones, A Margot Umpleby, David L Russell-Jones

Abstract

Objective: Insulin detemir lacks the usual propensity for insulin to cause weight gain. We investigated whether this effect was a result of reduced energy intake and/or increased energy expenditure.

Research design and methods: A 32-week, randomized crossover design trial was undertaken in 23 patients with type 1 diabetes. Patients on a basal-bolus regimen (with insulin aspart as the bolus insulin) were randomly assigned to insulin detemir or NPH insulin as a basal insulin for 16 weeks, followed by the other basal insulin for 16 weeks. At the end of each 16-week period, total energy expenditure, resting energy expenditure, diet-induced thermogenesis, activity energy expenditure, energy intake, weight change, glycemic control, hypoglycemic episodes, and hormones that affect satiety and fuel partitioning were measured.

Results: After 16 weeks, weight change was -0.69±1.85 kg with insulin detemir and +1.7±2.46 kg with NPH insulin (P<0.001). Total energy intake was significantly less with insulin detemir (2,016±501 kcal/day) than with NPH insulin (2,181±559 kcal/day) (P=0.026). There was no significant difference in any measure of energy expenditure, HbA1c percentage, or number of hypoglycemic episodes. Leptin was lower and resistin was higher with insulin detemir compared with NPH insulin (P=0.039, P=0.047). After the meal, ghrelin and pancreatic polypeptide levels (P=0.002, P=0.001) were higher with insulin detemir.

Conclusions: The reduced weight gain with insulin detemir compared with NPH insulin is attributed to reduced energy intake rather than increased energy expenditure. This may be mediated by a direct or indirect effect of insulin detemir on the hormones that control satiety.

Trial registration: ClinicalTrials.gov NCT00509925.

Figures

Figure 1
Figure 1
A: Changes in body weight after 16 weeks of treatment. B: Change in energy intake after 16 weeks. C: Change in total energy expenditure after 16 weeks. □, NPH insulin; ■, insulin detemir.
Figure 2
Figure 2
Mathematical model showing the relationships between changes in measured variables. +, Significant positive relationship; −, Significant negative relationship.

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