Metformin reduces weight, centripetal obesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30.

Abstract

We studied 31 nondiabetic, habitually or =5 years) morbidly obese subjects (mean SD body mass index BMI 43 8.7, median 43). Our specific aim was to determine whether metformin (2.55 g/d for 28 weeks) would ameliorate morbid obesity and reduce centripetal obesity; lipid and lipoprotein cholesterol, insulin, and leptin levels; and plasminogen activator inhibitor activity (PAI-Fx), risk factors for coronary heart disease (CHD). The patients were instructed to continue their prestudy dietary and exercise regimens without change. After 2 baseline visits 1 week apart, the 27 women and 4 men began receiving metformin, 2.55 g/d, which was continued for 28 weeks with follow-up visits at study weeks 5, 13, 21, and 29. Daily food intake was recorded by patients for 7 days before visits then reviewed with a dietitian. Kilocalories per day and per week were calculated. At each visit, fasting blood was obtained for measurement of lipid profile, insulin, leptin, and PAI-Fx. The mean SD kilocalories consumed per day, 1,951 661 at entry, fell by week 29 to 1,719 493 (P =.014) but did not differ at weeks 5, 13, and 21 from that at week 29 (P >.2). Weight fell from 258 62 pounds at entry to 245 54 pounds at week 29 (P =.0001). Girth was reduced from 51.8 6.2 to 49.2 4.5 inches (P =.0001). Waist circumference fell from 44.0 6.4 inches to 41.3 5.9 (P =.0001). The waist/hip ratio fell from 0.85 0.09 to 0.84 0.09 (P =.04). Fasting serum insulin, 28 15 microU/mL at entry, fell to 21 11 microU/mL at week 29 (P =.0001), and leptin fell from 79 33 ng/mL to 55 27 ng/mL (P =.0001). On metformin, there were linear trends in decrements in weight, girth, waist circumference, waist/hip ratio, insulin, and leptin throughout the study period (P 30, probably by virtue of its insulin-sensitizing action.

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