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

We studied 31 nondiabetic. habitually (greater than or equal to5 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 coproduct 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 coproduct 15 muU/mL at entry, fell to 21 +/- 11 muU/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 < .007). Low-density lipoprotein (LDL) cholesterol, 126 +/- 34 mg/dL at study entry, fell to 112 +/- 43 mg/dL at week 29 (P = .001), with a linear trend toward decreasing levels throughout (P = .036). By stepwise linear regression, the higher the entry weight, the larger the reduction in weight on metformin therapy (partial R-2 = 31%, P = .001). The greater the reduction in kilocalories consumed per day, the greater the decrease in weight on meformin therapy (partial W = 15%, P = .011). The higher the waist/hip ratio at entry, the greater its reduction on metformin therapy (partial R-2 = 11%. P = .004). The higher the entry serum leptin, the greater its reduction on metformin therapy (partial R-2 = 29%, P = .002). The geater the reduction in insulin on metformin, the greater the reduction in leptin (partial R-2 = 8%, P = .03), The higher the entry PAI-Fx, the greater the reduction in PAI-Fx on metformin (partial R-2 = 43%, P = .0001). Metformin safely and effectively reduces CHD risk factors (weight, fasting insulin, leptin, LDL cholesterol, centripetal obesity) in morbidly obese, nondiabetic subjects with BMI > 30, probably by virtue of its insulin-sensitizing action. Copyright (C) 2001 by W.B. Saunders Company.