Linagliptin improves endothelial function in patients with type 2 diabetes: A randomized study of linagliptin effectiveness on endothelial function

J Diabetes Investig. 2017 May;8(3):330-340. doi: 10.1111/jdi.12587. Epub 2016 Nov 21.

Abstract

Aims/introduction: The present multicenter, prospective, controlled, open and randomized three-arm parallel study was designed to compare the effects of linagliptin with those of metformin on endothelial function.

Materials and methods: Type 2 diabetes patients treated with 750 mg of metformin (hemoglobin A1c ≥6.0% and <8.0%, n = 96) were randomized to continue metformin 750 mg/day (control group, n = 29), metformin at 1,500 mg/day (metformin group, n = 26) and metformin 750 mg/day supplemented with linagliptin 5 mg/day (linagliptin add-on group, n = 29) and treated for 16 weeks. Vascular endothelial function was evaluated by flow-mediated dilation. The primary end-point was changes in flow-mediated dilation at 16 weeks relative to baseline.

Results: Linagliptin significantly improved flow-mediated dilation from baseline (4.9 ± 2.7%) to 16 weeks (6.3 ± 2.7%, P < 0.05), whereas the other groups did not show any changes. Hemoglobin A1c at 16 weeks was significantly lower in the metformin and linagliptin add-on groups compared with the control (6.6 ± 0.6%, 6.5 ± 0.5% and 7.0 ± 0.6%, respectively). Single and multiple regression analyses showed that apolipoprotein B correlated significantly with change in flow-mediated dilation, and apolipoprotein B was decreased only in the linagliptin add-on group (-6.0 ± 11.3 mg/dL, P < 0.01).

Conclusions: Linagliptin for 16 weeks improved endothelial function with a modest improvement in glycemic control. This effect was mediated, at least in part, by reduction in apolipoprotein B. Linagliptin has a protective role on endothelial function in patients with type 2 diabetes with moderate hyperglycemia.

Keywords: Endothelial function; Linagliptin; Type 2 diabetes.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / drug therapy*
  • Diabetes Mellitus, Type 2 / complications*
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Linagliptin / therapeutic use*
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Prospective Studies
  • Treatment Outcome

Substances

  • Hypoglycemic Agents
  • Linagliptin
  • Metformin