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Randomized Controlled Trial
. 2017 May;11(3):602-610.
doi: 10.1177/1932296817699847. Epub 2017 Mar 28.

Use of Sitagliptin With Closed-Loop Technology to Decrease Postprandial Blood Glucose in Type 1 Diabetes

Lisa J Underland  1 , Jeniece Trast Ilkowitz  1   2 , Ranjitha Katikaneni  1 , Amy Dowd  1 , Rubina A Heptulla  1
Affiliations
Randomized Controlled Trial

Use of Sitagliptin With Closed-Loop Technology to Decrease Postprandial Blood Glucose in Type 1 Diabetes

Lisa J Underland et al. J Diabetes Sci Technol. 2017 May.

Abstract

Background: Postprandial hyperglycemia poses a challenge to closed-loop systems. Dipeptidyl peptidase-4 (DPP-4) inhibitors, like sitagliptin, reduce postprandial glucose concentrations in patients with type 2 diabetes. The objective of this study was to assess sitagliptin's role in type 1 diabetes (T1DM) as an adjunct therapy in reducing postprandial blood glucose with an insulin-only closed-loop system.

Methods: This was a randomized, double-blinded, placebo controlled, crossover design trial. The participants were18-35 years old, had T1DM, and an HbA1c of ≤ 8.5%. A dose determination study included eight subjects with T1DM. There were three study visits. Four hours after receiving study drug (placebo, sitagliptin 50 mg, sitagliptin 100 mg), subjects underwent a mixed meal tolerance test with assessment of hormone concentrations. In a second study, 15 subjects underwent two visits receiving either placebo or 100 mg of sitagliptin plus an insulin only closed-loop system for 25 hours with timed meals. Blood glucose and other hormone concentrations were analyzed using repeated measures ANOVA.

Results: For the dose determination study, sitagliptin 100 mg resulted in reduced postprandial blood glucose ( P = .006). For the closed-loop study, glucose concentrations were lower in the treatment group, most prominently during the first two study meals ( P = .03). There was no difference in glucagon concentrations, but insulin concentrations and insulin delivery were lower in the treatment group.

Conclusions: Sitagliptin may be considered as an adjunct therapy in a closed-loop setting. Larger studies are needed to determine the role of oral agents like sitagliptin to lower postprandial hyperglycemia with closed loop.

Keywords: artificial pancreas; closed loop; sitagliptin; type 1 diabetes.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RAH is a shareholder in Thermalin Diabetes and a consultant for Lexicon, Merck, and Mannkind. For all other authors, the disclosures are “none.”

Figures

Figure 1.
Figure 1.
Study Design. (A) Dose determination study schematic. (B) Closed-loop study schematic.
Figure 2.
Figure 2.
Dose determination/open loop. (A) Glucose concentrations between the control and the two treatment groups. (B) Total AUC for glucose concentrations between the control and the two treatment groups.
Figure 3.
Figure 3.
(A, C, E) Glucose, insulin, and glucagon concentrations in the control vs sitagliptin treatment arms. (B, D, F) Total area under curve (AUC) for glucose, insulin, and glucagon between the control and treatment groups.
See this image and copyright information in PMC

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