Elsevier

Molecular Metabolism

Volume 9, March 2018, Pages 168-175
Molecular Metabolism

Original Article
Efficacy of vildagliptin for prevention of postpartum diabetes in women with a recent history of insulin-requiring gestational diabetes: A phase II, randomized, double-blind, placebo-controlled study

https://doi.org/10.1016/j.molmet.2017.12.015Get rights and content
Under a Creative Commons license
open access

Highlights

  • Treatment with vildagliptin suggested positive effects on β-cell function and HbA1c.

  • Treatment with vildagliptin was safe.

  • Contraindication of vildagliptin during lactation led to exclusion of women with early postpartum diabetes.

  • Slow enrolment and high drop-out rates are major challenges in studies of women with GDM.

Abstract

Objective

Women with insulin-requiring gestational diabetes mellitus (GDM) are at high risk of developing diabetes within a few years postpartum. We implemented this phase II study to test the hypothesis that vildagliptin, a dipeptidyl peptidase-4 inhibitor, is superior to placebo in terms of reducing the risk of postpartum diabetes.

Methods

Women with insulin-requiring GDM were randomized to either placebo or 50 mg vildagliptin twice daily for 24 months followed by a 12-month observation period (EudraCT: 2007-000634-39). Both groups received lifestyle counseling. The primary efficacy outcomes were the diagnosis of diabetes (American Diabetes Association (ADA) criteria) or impaired fasting glucose (IFG)/impaired glucose tolerance (IGT).

Results

Between 2008 and 2015, 113 patients (58 vildagliptin, 55 placebo) were randomized within 2.2–10.4 (median 8.6) months after delivery. At the interim analysis, nine diabetic events and 28 IFG/IGT events had occurred. Fifty-two women withdrew before completing the treatment phase. Because of the low diabetes rate, the study was terminated. Lifestyle adherence was similar in both groups. At 24 months, the cumulative probability of postpartum diabetes was 3% and 5% (hazard ratio: 1.03; 95% confidence interval: 0.15–7.36) and IFG/IGT was 43% and 22% (hazard ratio: 0.55; 95% confidence interval: 0.26–1.19) in the placebo and vildagliptin groups, respectively. Vildagliptin was well tolerated with no unexpected adverse events.

Conclusions

The study did not show significant superiority of vildagliptin over placebo in terms of reducing the risk of postpartum diabetes. However, treatment was safe and suggested some improvements in glycemic control, insulin resistance, and β-cell function. The study identified critical issues in performing clinical trials in the early postpartum period in women with GDM hampering efficacy assessments. With this knowledge, we have set a basis for which properly powered trials could be performed in women with recent GDM.

Trial registration number at ClinicalTrials.gov

NCT01018602.

Keywords

Gestational diabetes mellitus
Prevention
Dipeptidyl peptidase-4 inhibitor
Postpartum diabetes
Randomized controlled trial
Life-style

Abbreviations

DPP4 inhibitor
dipeptidyl peptidase-4 inhibitor
GDM
gestational diabetes mellitus
GIP
glucose-dependent insulinotropic polypeptide
GLP-1
Glucagon-like peptide-1
IFG
impaired fasting glucose
IGT
impaired glucose tolerance
ITT
intention-to-treat

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