Journal
DIABETIC MEDICINE
Volume 28, Issue 10, Pages 1176-1181Publisher
WILEY
DOI: 10.1111/j.1464-5491.2011.03331.x
Keywords
dipeptidyl peptidase IV inhibitor; glucagon-like peptide 1; HbA(1c); sitagliptin; Type 1 diabetes
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Funding
- Merck Inc.
- Merck Inc. (Whitehouse Station, NJ, USA)
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Aims Patients with Type 1 diabetes have significantly elevated postprandial glucagon secretion. Dipeptidyl peptidase IV inhibitors improve HbA(1c) by several mechanisms, including increasing glucagon-like peptide 1 and glucose-dependent insulinotropic peptide concentrations, which decreases postprandial rises in glucagon in both Type 1 and Type 2 diabetes. This study evaluates the clinical implications of sitagliptin in adult patients with Type 1 diabetes. Methods This investigator-initiated, double-blind, randomized, crossover, 8-week, pilot study enrolled 20 adult subjects with Type 1 diabetes. Subjects received sitagliptin 100 mg/day or placebo for 4 weeks and then crossed over. Outcomes included 2-h postprandial blood glucose and 24-h area under the curve changes in glucose measurements from continuous glucose monitoring, HbA1c, fructosamine and insulin dose. Results Sitagliptin significantly reduced blood glucose (2-h postprandial and 24-h area under the curve) despite reduced total and prandial insulin dose. Based on continuous glucose monitor findings, sitagliptin improved measures of glycaemic control, including mean blood glucose (-0.6 mmol/l; P = 0.012) and time in euglycaemic range 4.4-7.8 mmol/l (0.4 +/- 0.2 h; P = 0.046). Significant reductions were also observed in M100, Glycemic Risk Assessment Diabetes Equation (GRADE) and J-index. After controlling for period, treatment and insulin dose, the HbA1c was also significantly reduced [-0.27 +/- 0.11% (-2.91 +/- 1.16 mmol/mol); P = 0.025] when patients were taking sitagliptin. Conclusions Sitagliptin significantly improved overall glucose control, including postprandial and 24-h glucose control, in adult patients with Type 1 diabetes, while significantly reducing prandial insulin requirements. Further investigation is warranted in patients with Type 1 diabetes in a larger cohort designed to assess both clinical outcomes and mechanism of action.
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