The Role of Metformin Response in Lipid Metabolism in Patients with Recent-Onset Type 2 Diabetes: HbA1c Level as a Criterion for Designating Patients as Responders or Nonresponders to Metformin

PLoS One. 2016 Mar 15;11(3):e0151543. doi: 10.1371/journal.pone.0151543. eCollection 2016.

Abstract

Background: In this study, we investigated whether response to metformin, the most frequently drug for diabetes treatment, influences the therapeutic effects of antilipidemic medication in newly diagnosed patients with type 2 diabetes mellitus (T2DM).

Methods: A total of 150 patients with T2DM were classified into two groups following 3 months of metformin therapy (1000 mg twice daily): responders (patients showing ≥1% reduction in HbA1c from baseline) and nonresponders (patients showing <1% reduction in HbA1c from baseline). The patients received atorvastatin 20 mg, gemfibrozil 300 mg, or atorvastatin 20 mg and gemfibrozil 300 mg daily.

Principal findings: HbA1c and fasting glucose levels were significantly different between baseline and 3 months among responders receiving atorvastatin; however, these differences were not statistically significant in nonresponders. Atherogenic ratios of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C; p = 0.002), total cholesterol to HDL-C (TC/HDL-C; p<0.001) and AIP (the atherogenic index of plasma; p = 0.004) decreased significantly in responders receiving atorvastatin than in nonresponders. Moreover, responders receiving atorvastatin showed a significant increase in HDL-C levels but nonresponders receiving atorvastatin did not (p = 0.007). The multivariate model identified a significant association between metformin response (as the independent variable) and TG, TC, HDL-C and LDL-C (dependent variables; Wilk's λ = 0.927, p = 0.036).

Conclusions: Metformin response affects therapeutic outcomes of atorvastatin on atherogenic lipid markers in patients newly diagnosed with T2DM. Metformin has a greater impact on BMI in responders of metformin compared to nonresponders. Adoption of better therapeutic strategies for reducing atherogenic lipid markers may be necessary for metformin nonresponders.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atorvastatin / pharmacokinetics
  • Atorvastatin / pharmacology*
  • Atorvastatin / therapeutic use
  • Biological Transport / drug effects
  • Blood Glucose / analysis
  • Blood Pressure / drug effects
  • Body Mass Index
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Monitoring
  • Drug Resistance
  • Drug Synergism
  • Drug Therapy, Combination
  • Dyslipidemias / blood
  • Dyslipidemias / drug therapy*
  • Dyslipidemias / etiology
  • Female
  • Gemfibrozil / pharmacology*
  • Gemfibrozil / therapeutic use
  • Glycated Hemoglobin / analysis*
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use
  • Hypolipidemic Agents / pharmacology*
  • Hypolipidemic Agents / therapeutic use
  • Male
  • Metformin / pharmacology*
  • Metformin / therapeutic use
  • Middle Aged

Substances

  • Blood Glucose
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Hypolipidemic Agents
  • Metformin
  • Atorvastatin
  • Gemfibrozil

Grants and funding

This study was funded by Mazandaran University of Medical Sciences.