Treatment with metformin and a dipeptidyl peptidase-4 inhibitor elevates apelin levels in patients with type 2 diabetes mellitus

Drug Des Devel Ther. 2015 Aug 14:9:4679-83. doi: 10.2147/DDDT.S85740. eCollection 2015.

Abstract

Background: The objective of this study was to assess the effects of metformin monotherapy or combined treatment with a dipeptidyl peptidase-4 inhibitor (vildagliptin) on apelin levels in patients with type 2 diabetes mellitus.

Methods: Twenty-five patients with poor glycemic control (glycosylated hemoglobin >6.5% [48 mmol/mol]) taking 1,000 mg of metformin daily and 25 healthy controls matched for age and body mass index were enrolled in this study. Anthropometric parameters, glycemic and lipid profile, insulin resistance (homeostasis model assessment of insulin resistance index), and apelin levels were measured at baseline and at 12-week and 24-week visits.

Results: At baseline, apelin levels were higher in the T2DM patients than in the controls (1.93±1.81 ng/mL versus 6.09±4.90 ng/mL; P<0.05). After 12 weeks, when vildagliptin was added, fasting blood glucose and glycosylated hemoglobin decreased, and apelin levels increased further (from 6.09±4.90 ng/mL to 24.23±12.59 ng/mL; P<0.05). Follow-up at 24 weeks showed no further improvement in the glycemic profile and no further increase in apelin levels.

Conclusion: Both metformin and vildagliptin favorably changed glycemic indices and apelin levels. For patients inadequately controlled on a low dose of metformin, addition of vildagliptin may be helpful.

Keywords: adipocytokine; antidiabetic drug; glucagon-like peptides; glucose-dependent insulinotropic polypeptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / therapeutic use
  • Adult
  • Apelin
  • Biomarkers / blood
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / enzymology
  • Dipeptidyl Peptidase 4 / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Resistance
  • Intercellular Signaling Peptides and Proteins / blood
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Nitriles / therapeutic use*
  • Pyrrolidines / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Up-Regulation
  • Vildagliptin

Substances

  • APLN protein, human
  • Apelin
  • Biomarkers
  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Intercellular Signaling Peptides and Proteins
  • Nitriles
  • Pyrrolidines
  • hemoglobin A1c protein, human
  • Metformin
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4
  • Vildagliptin
  • Adamantane