Exenatide or glimepiride added to metformin on metabolic control and on insulin resistance in type 2 diabetic patients

Eur J Pharmacol. 2011 Sep;666(1-3):251-6. doi: 10.1016/j.ejphar.2011.05.051. Epub 2011 Jun 1.


The aim of this study was to evaluate the effect of exenatide compared to glimepiride on body weight, glycemic control and insulin resistance in type 2 diabetic patients taking metformin. One hundred and eleven patients with uncontrolled type 2 diabetes mellitus and intolerant to metformin at the highest dosages (2500-3000 mg/day) were enrolled in this study. Patients were randomized to receive exenatide 5 μg twice a day or glimepiride 1mg three times a day and titrated after 1 month to exenatide 10 μg twice a day or glimepiride 2mg three times a day for 12 months in a randomized, single-blind, controlled study. We evaluated at the baseline and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), HbA(1c), glycemic control, fasting plasma insulin, homeostasis model assessment insulin resistance index (HOMA-IR) index, adiponectin, tumor necrosis factor-α, and high sensitivity-C reactive protein. Both treatments gave a similar improvement of glycemic control, without any differences between the two groups. Only exenatide gave a decrease of BMI, insulin resistance parameters such as fasting plasma insulin, HOMA-IR, and adiponectin and a decrease of inflammatory parameters such as tumor necrosis factor-α, and high sensitivity-C reactive protein. Furthermore, the values obtained with exenatide were significantly better than the values recorded with glimepiride. We can conclude that exenatide was better than glimepiride in improving insulin resistance and inflammatory state. Furthermore, adiponectin increase, and tumor necrosis factor-α reduction seem to be related to weight loss obtained with exenatide.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Biomarkers / metabolism
  • Blood Glucose / metabolism
  • Body Mass Index
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Exenatide
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Inflammation / metabolism
  • Insulin Resistance*
  • Male
  • Metformin / pharmacology*
  • Metformin / therapeutic use
  • Middle Aged
  • Peptides / pharmacology*
  • Peptides / therapeutic use
  • Sulfonylurea Compounds / pharmacology*
  • Sulfonylurea Compounds / therapeutic use
  • Venoms / pharmacology*
  • Venoms / therapeutic use


  • Biomarkers
  • Blood Glucose
  • Glycated Hemoglobin A
  • Peptides
  • Sulfonylurea Compounds
  • Venoms
  • hemoglobin A1c protein, human
  • glimepiride
  • Metformin
  • Exenatide