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 ([ge ]5 years) morbidly obese subjects (mean [plusmn] SD body mass index [BMI] 43 [plusmn] 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 [plusmn] SD kilocalories consumed per day, 1,951 [plusmn] 661 at entry, fell by week 29 to 1,719 [plusmn] 493 ( P = .014) but did not differ at weeks 5, 13, and 21 from that at week 29 ( P [gt ] .2). Weight fell from 258 [plusmn] 62 pounds at entry to 245 [plusmn] 54 pounds at week 29 ( P = .0001). Girth was reduced from 51.8 [plusmn] 6.2 to 49.2 [plusmn] 4.5 inches ( P = .0001). Waist circumference fell from 44.0 [plusmn] 6.4 inches to 41.3 [plusmn] 5.9 ( P = .0001). The waist/hip ratio fell from 0.85 [plusmn] 0.09 to 0.84 [plusmn] 0.09 ( P = .04). Fasting serum insulin, 28 [plusmn] 15 [mu ]U/mL at entry, fell to 21 [plusmn] 11 [mu ]U/mL at week 29 ( P = .0001), and leptin fell from 79 [plusmn] 33 ng/mL to 55 [plusmn] 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 [lt ] .007). Low-density lipoprotein (LDL) cholesterol, 126 [plusmn] 34 mg/dL at study entry, fell to 112 [plusmn] 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 R 2 = 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 [gt ] 30, probably by virtue of its insulin-sensitizing action.