Effects of Conjugated Linoleic Acid and Metformin on Insulin Sensitivity in Obese Children: Randomized Clinical Trial

J Clin Endocrinol Metab. 2017 Jan 1;102(1):132-140. doi: 10.1210/jc.2016-2701.


Context: Insulin resistance precedes metabolic syndrome abnormalities and may promote cardiovascular disease and type 2 diabetes in children with obesity. Results of lifestyle modification programs have been discouraging, and the use of adjuvant strategies has been necessary.

Objective: This study aimed to evaluate the effects of metformin and conjugated linoleic acid (CLA) on insulin sensitivity, measured via euglycemic-hyperinsulinemic clamp technique and insulin pathway expression molecules in muscle biopsies of children with obesity.

Design: A randomized, double-blinded, placebo-controlled clinical trial was conducted.

Setting: Children with obesity were randomly assigned to receive metformin, CLA, or placebo.

Results: Intervention had a positive effect in all groups. For insulin sensitivity Rd value (mg/kg/min), there was a statistically significant difference between the CLA vs placebo (6.53 ± 2.54 vs 5.05 ± 1.46, P = 0.035). Insulinemia and homeostatic model assessment of insulin resistance significantly improved in the CLA group (P = 0.045). After analysis of covariance was performed and the influence of body mass index, age, Tanner stage, prescribed diet, and fitness achievement was controlled, a clinically relevant effect size on insulin sensitivity remained evident in the CLA group (37%) and exceeded lifestyle program benefits. Moreover, upregulated expression of the insulin receptor substrate 2 was evident in muscle biopsies of the CLA group.

Conclusions: Improvement of insulin sensitivity, measured via euglycemic-hyperinsulinemic clamp and IRS2 upregulation, favored patients treated with CLA.

Trial registration: ClinicalTrials.gov NCT02063802.

Publication types

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

MeSH terms

  • Adolescent
  • Biomarkers / analysis
  • Blood Glucose / analysis
  • Body Composition
  • Cardiovascular Diseases / prevention & control*
  • Child
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / blood
  • Insulin Resistance*
  • Linoleic Acids, Conjugated / therapeutic use*
  • Lipids / analysis
  • Male
  • Metabolic Syndrome / prevention & control*
  • Metformin / therapeutic use*
  • Obesity / complications
  • Obesity / drug therapy*
  • Prognosis


  • Biomarkers
  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Linoleic Acids, Conjugated
  • Lipids
  • Metformin

Associated data

  • ClinicalTrials.gov/NCT02063802