Acute antihyperglycemic mechanisms of metformin in NIDDM. Evidence for suppression of lipid oxidation and hepatic glucose production
Abstract
To establish the antihyperglycemic mechanisms of metformin in non-insulin-dependent diabetes mellitus (NIDDM) independently of the long-term, aspecific effects of removal of glucotoxicity, 21 NIDDM subjects (14 obese, 7 nonobese) were studied on two separate occasions, with an isoglycemic (plasma glucose approximately 9 mM) hyperinsulinemic (two-step insulin infusion, 2 h each, at the rate of 4 and 40 mU.m-2.min-1) clamp combined with [3-3H]glucose infusion and indirect calorimetry, after administration of either metformin (500 mg per os, at -5 and -1 h before the clamp) or placebo. Compared with placebo, hepatic glucose production (HGP) decreased approximately 30% more after metformin (from 469 +/- 50 to 330 +/- 54 mumol/min), but glucose uptake did not increase. Metformin suppressed free fatty acids (FFAs) by approximately 17% (from 0.42 +/- 0.04 to 0.35 +/- 0.04 mM) and lipid oxidation by approximately 25% (from 4.5 +/- 0.4 to 3.4 +/- 0.4 mumol.kg-1.min-1) and increased glucose oxidation by approximately 16% (from 16.2 +/- 1.4 to 19.3 +/- 1.3 mumol.kg-1.min-1) compared with placebo (P < 0.05), but did not affect nonoxidative glucose metabolism, protein oxidation, or total energy expenditure. Suppression of FFA and lipid oxidation after metformin correlated with suppression of HGP (r = 0.70 and r = 0.51, P < 0.001). The effects of metformin in obese and nonobese subjects were no different. We conclude that the specific, antihyperglycemic effects of metformin in the…
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Evidence Hub reads this as a clinical trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 21 participants or records.
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