Effects of 1-year orlistat treatment compared to placebo on insulin resistance parameters in patients with type 2 diabetes

J Clin Pharm Ther. 2012 Apr;37(2):187-95. doi: 10.1111/j.1365-2710.2011.01280.x. Epub 2011 Aug 4.

Abstract

What is known and objective: The behavioural approach is usually slow and not always sufficient to achieve optimal targets in weight and metabolic control in obese diabetic patients, and a pharmacological treatment is often necessary. The aim of this study was to compare the effects of orlistat and placebo on body weight, glycaemic and lipid profile and insulin resistance in patients with type 2 diabetes.

Methods: Two hundred and fifty-four obese, diabetic patients were enrolled in this study and randomized to take orlistat 360mg or placebo for 1year. We evaluated at baseline and after 3, 6, 9 and 12months body weight, waist circumference (WC), body mass index (BMI), glycated haemoglobin (HbA(1c) ), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), lipid profile, retinol-binding protein-4 (RBP-4), resistin, visfatin and high-sensitivity C-reactive protein (Hs-CRP).

Results and discussion: We observed a significant reduction in body weight, WC, BMI, lipid profile, RBP-4 and visfatin in the orlistat group but not in control group. Faster improvements in HbA(1c) , PPG, FPI, HOMA-IR, resistin and Hs-CRP were recorded with orlistat than with placebo. A similar decrease in FPG was seen in the two groups. Significant predictors of change in insulin resistance (HOMA-IR) were RBP-4 and resistin concentration in the orlistat group (r=-0·53, P<0·05, and r=-0·59, P<0·01, respectively).

What is new and conclusion: To the best of our knowledge, this is the first study investigating the effect of orlistat on insulin resistance and markers of inflammation. Orlistat improved lipid profile and led to faster glycaemic control and insulin resistance parameters than the control, without any serious adverse event. Orlistat also improved RBP-4 and visfatin, effects not observed with placebo.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Anti-Obesity Agents / adverse effects
  • Anti-Obesity Agents / pharmacology
  • Anti-Obesity Agents / therapeutic use*
  • Biomarkers / metabolism
  • Blood Glucose / drug effects
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / physiopathology
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Insulin Resistance
  • Lactones / adverse effects
  • Lactones / pharmacology
  • Lactones / therapeutic use*
  • Lipids / blood
  • Male
  • Middle Aged
  • Nicotinamide Phosphoribosyltransferase / drug effects
  • Nicotinamide Phosphoribosyltransferase / metabolism
  • Obesity / complications
  • Obesity / drug therapy*
  • Orlistat
  • Retinol-Binding Proteins, Plasma / drug effects
  • Retinol-Binding Proteins, Plasma / metabolism

Substances

  • Anti-Obesity Agents
  • Biomarkers
  • Blood Glucose
  • Lactones
  • Lipids
  • RBP4 protein, human
  • Retinol-Binding Proteins, Plasma
  • Orlistat
  • Nicotinamide Phosphoribosyltransferase