Treatment with anagliptin, a DPP-4 inhibitor, decreases FABP4 concentration in patients with type 2 diabetes mellitus at a high risk for cardiovascular disease who are receiving statin therapy

Cardiovasc Diabetol. 2020 Jun 15;19(1):89. doi: 10.1186/s12933-020-01061-0.

Abstract

Background: Fatty acid-binding protein 4 (FABP4) acts as a novel adipokine, and elevated FABP4 concentration is associated with obesity, insulin resistance and atherosclerosis. Dipeptidyl peptidase-4 (DPP-4) inhibitors, a class of antidiabetic drugs, have distinct structures among the drugs, possibly leading to a drug class effect and each drug effect. Sitagliptin, a DPP-4 inhibitor, has been reported to decrease FABP4 concentration in drug-naïve and sulfonylurea-treated patients with type 2 diabetes mellitus. Anagliptin, another DPP-4 inhibitor, was shown to decrease low-density lipoprotein cholesterol (LDL-C) level to a greater extent than that by sitagliptin in the Randomized Evaluation of Anagliptin vs. Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial.

Aim and methods: As a sub-analysis study using data obtained from the REASON trial, we investigated the effects of treatment with anagliptin (n = 148, male/female: 89/59) and treatment with sitagliptin (n = 159, male/female: 93/66) for 52 weeks on FABP4 concentration in patients with type 2 diabetes mellitus at a high risk for cardiovascular events who were receiving statin therapy.

Results: The DPP-4 inhibitor had been administered in 82% of the patients in the anagliptin group and 81% of the patients in sitagliptin group prior to randomization. Serum FABP4 level was significantly decreased by 7.9% by treatment with anagliptin (P = 0.049) and was not significantly decreased by treatment with sitagliptin (P = 0.660). Change in FABP4 level was independently associated with basal FABP4 level and changes in waist circumference and creatinine after adjustment of age, sex and the treatment group.

Conclusion: Anagliptin decreases serum FABP4 concentration independent of change in hemoglobin A1c or LDL-C in patients with type 2 diabetes mellitus and dyslipidemia who are on statin therapy. Trial registration ClinicalTrials.gov number NCT02330406. Registered January 5, 2015, https://clinicaltrials.gov/ct2/show/NCT02330406.

Keywords: Anagliptin; Dipeptidyl peptidase-4 inhibitor; Fatty acid-binding protein; Sitagliptin.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / prevention & control*
  • Cholesterol, LDL / blood
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Down-Regulation
  • Dyslipidemias / blood
  • Dyslipidemias / diagnosis
  • Dyslipidemias / drug therapy*
  • Dyslipidemias / epidemiology
  • Fatty Acid-Binding Proteins / blood*
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Male
  • Middle Aged
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • Blood Glucose
  • Cholesterol, LDL
  • Dipeptidyl-Peptidase IV Inhibitors
  • FABP4 protein, human
  • Fatty Acid-Binding Proteins
  • Glycated Hemoglobin A
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrimidines
  • hemoglobin A1c protein, human
  • anagliptin

Associated data

  • ClinicalTrials.gov/NCT02330406