Metabolic effects of metformin in patients with impaired glucose tolerance

Diabet Med. 2001 Jul;18(7):578-83. doi: 10.1046/j.1464-5491.2001.00539.x.


Aims: To assess the effect of metformin on insulin sensitivity, glucose tolerance and components of the metabolic syndrome in patients with impaired glucose tolerance (IGT).

Methods: Forty first-degree relatives of patients with Type 2 diabetes fulfilling WHO criteria for IGT and participating in the Botnia study in Finland were randomized to treatment with either metformin 500 mg b.i.d. or placebo for 6 months. An oral glucose tolerance test (OGTT) and a euglycaemic hyperinsulinaemic clamp in combination with indirect calorimetry was performed at 0 and 6 months. The patients were followed after stopping treatment for another 6 months in an open trial and a repeat OGTT was performed at 12 months.

Results: Metformin treatment resulted in a 20% improvement in insulin-stimulated glucose metabolism (from 28.7 +/- 13 to 34.4 +/- 10.7 micromol/kg fat-free mass (FFM)/min) compared with placebo (P = 0.01), which was primarily due to an increase in glucose oxidation (from 16.6 +/- 3.6 to 19.1 +/- 4.4 micromol/kg FFM; P = 0.03) These changes were associated with a minimal improvement in glucose tolerance, which was maintained after 12 months.

Conclusions: Metformin improves insulin sensitivity in subjects with IGT primarily by reversal of the glucose fatty acid cycle. Obviously large multicentre studies are needed to establish whether these effects are sufficient to prevent progression to manifest Type 2 diabetes and associated cardiovascular morbidity and mortality. Diabet. Med. 18, 578-583 (2001)

Publication types

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

MeSH terms

  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Blood Pressure
  • Body Weight
  • Diabetes Mellitus, Type 2 / genetics
  • Energy Metabolism
  • Fatty Acids, Nonesterified / blood
  • Glucose Clamp Technique
  • Glucose Intolerance / blood*
  • Glucose Tolerance Test
  • Humans
  • Hyperinsulinism / blood
  • Hypoglycemic Agents / therapeutic use
  • Infusions, Intravenous
  • Insulin / administration & dosage
  • Insulin / pharmacology
  • Lipids / blood
  • Metformin / therapeutic use*
  • Weight Loss


  • Blood Glucose
  • Fatty Acids, Nonesterified
  • Hypoglycemic Agents
  • Insulin
  • Lipids
  • Metformin