Metformin decreases food consumption and induces weight loss in subjects with obesity with type II non-insulin-dependent diabetes.

Metformin often promotes weight loss in patients with obesity with non-insulin-dependent diabetes mellitus (NIDDM). The mechanism may be attributed to decreased food intake. This study has tested the effect of metformin on satiety and its efficacy in inducing weight loss. Twelve diet-treated NIDDM women with obesity were randomly given two dose levels (850 mg or 1700 mg) of metformin or placebo at 0800 for three consecutive days followed by a meal test on the third day on three occasions using a 3x3 Latin square design. The number of sandwich canapes eaten in three consecutive 10-minute periods beginning at 1400 hours was used to quantitate food intake, and the level of subjective hunger was rated just before the sandwich meal with a linear analogue hunger rating scale at 1400 after a 6-hour fast. The prior administration of metformin produced a reduction in calorie intake after each of the two doses of metformin treatment. The 1700-mg metformin dose had the most marked appetite suppressant action. Similarly, hunger ratings were significantly lowered after metformin, and the effect was most pronounced after the administration of 1700 mg of metformin. To assess the efficacy of metformin in reducing bodyweight, 48 diet-treated NIDDM women with obesity who had failed to lose weight by diet therapy were first placed on a 1200-kcal ADA (American Diabetes Association) diet before being randomized to receive either metformin (850 mg) or placebo twice daily in a double-blind fashion for 24 weeks. A 4-week single-blind placebo lead-in period preceded and a 6-week single-blind placebo period followed the 24-week double-blind treatment period. Subjects treated with metformin continued to lose weight throughout 24 weeks of treatment; their mean maximum weight loss was 8 kg greater than that of the placebo group, with corresponding lower HbA1C and fasting blood glucose levels at the end of the active treatment period. These results indicate that metformin decreases calorie intake in a dose-dependent manner and leads to a reduction in bodyweight in NIDDM patients with obesity.

[1]  D. Jakubowicz,et al.  Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. , 1996, The New England journal of medicine.

[2]  E. Ferrannini,et al.  Acute Antihyperglycemic Mechanisms of Metformin in NIDDM: Evidence for Suppression of Lipid Oxidation and Hepatic Glucose Production , 1994, Diabetes.

[3]  R. Considine,et al.  Serum immunoreactive-leptin concentrations in normal-weight and obese humans. , 1996, The New England journal of medicine.

[4]  J. Lord,et al.  Effect of metformin on insulin receptor binding and glycaemic control in type II diabetes. , 1983, British medical journal.

[5]  H. Rüdiger,et al.  Biguanide treatment increases the number of insulin-receptor sites on human erythrocytes. , 1981, The New England journal of medicine.

[6]  J. Bue-Valleskey,et al.  The role of neuropeptide Y in the antiobesity action of the obese gene product , 1995, Nature.

[7]  J. Morley Neuropeptide regulation of appetite and weight. , 1987, Endocrine reviews.

[8]  S. P. Grossman The role of glucose, insulin and glucagon in the regulation of food intake and body weight , 1986, Neuroscience & Biobehavioral Reviews.

[9]  E. Rolls,et al.  Pleasantness changes and food intake in a varied four-course meal , 1984, Appetite.

[10]  C. Bailey Biguanides and NIDDM , 1992, Diabetes Care.

[11]  R. Jung,et al.  Energy expenditure in non-insulin dependent diabetic subjects on metformin or sulphonylurea therapy. , 1987, Clinical science.

[12]  A. Mushlin,et al.  A double-blind clinical trial in weight control. Use of fenfluramine and phentermine alone and in combination. , 1984, Archives of internal medicine.

[13]  G Dailey,et al.  Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. , 1995, The New England journal of medicine.

[14]  Stone Db Treatment of the obese diabetic patient. , 1967 .

[15]  B. Clarke,et al.  Comparison of metformin and chlorpropamide in non-obese, maturity-onset diabetics uncontrolled by diet. , 1977, British medical journal.

[16]  R. Campbell,et al.  Hunger in humans induced by 2-deoxy-D-glucose: glucoprivic control of taste preference and food intake. , 1977, Science.

[17]  W. Klein Sulfonylurea-metformin-combination versus sulfonylurea-insulin-combination in secondary failures of sulfonylurea monotherapy. Results of a prospective randomized study in 50 patients. , 1991, Diabete & metabolisme.

[18]  I. Stein,et al.  Vagotomy and the hunger-producing action of insulin in man. , 1948, Journal of applied physiology.

[19]  S. Woods,et al.  Insulin in the brain: a hormonal regulator of energy balance. , 1992, Endocrine reviews.

[20]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1994, Nature.

[21]  Hermann Ls Metformin: a review of its pharmacological properties and therapeutic use. , 1979 .

[22]  R. Vigneri,et al.  Treatment of NIDDM patients with secondary failure to glyburide: comparison of the addition of either metformin or bed-time NPH insulin to glyburide. , 1991, Diabete & metabolisme.

[23]  T. Koschinsky,et al.  Oral antidiabetic combination therapy with sulphonylureas and metformin. , 1991, Diabete & metabolisme.

[24]  L. S. Hermann,et al.  Comparative efficacy of metformin and glibenclamide in patients with non-insulin-dependent diabetes mellitus. , 1991, Diabete & metabolisme.

[25]  G. Bray,et al.  A randomized double-blind clinical trial of fluoxetine in obese diabetics. , 1992, International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity.

[26]  L. J. Duncan,et al.  Weight-reducing Effect of Diguanides in Obese Non-diabetic Women , 1969, British medical journal.

[27]  G. Bray,et al.  Insulin secretion in hypothalamic obesity: diurnal variation and the effect of naloxone. , 1993, Obesity research.

[28]  S. Woods,et al.  Intraventricular insulin reduces food intake and body weight of lean but not obese zucker rats , 1986, Appetite.

[29]  L. Campfield,et al.  Insulin normalization as an approach to the pharmacological treatment of obesity. , 1995, Obesity research.

[30]  D. Porte,et al.  Insulin binding to brain capillaries is reduced in genetically obese, hyperinsulinemic Zucker rats , 1990, Peptides.

[31]  B. Clarke,et al.  Comparison of chlorpropamide and metformin treatment on weight and blood-glucose response of uncontrolled obese diabetics. , 1968, Lancet.

[32]  B. Guy-grand,et al.  INTERNATIONAL TRIAL OF LONG-TERM DEXFENFLURAMINE IN OBESITY , 1989, The Lancet.

[33]  A. Stunkard,et al.  The anorectic effect of dexamphetamine sulphate. , 1968, British journal of pharmacology and chemotherapy.

[34]  I. Leck,et al.  PREVALENCE AND DURATION OF UNDETECTED BREAST CANCER , 1975, The Lancet.

[35]  H. Kissileff,et al.  A Quadratic Equation Adequately Describes the Cumulative Food Intake Curve in Man , 1982, Appetite.