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Exp Clin Endocrinol Diabetes 2013; 121(01): 27-31
DOI: 10.1055/s-0032-1327734
Article
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Effectiveness of Metformin on Weight Loss in Non-Diabetic Individuals with Obesity

C. Seifarth
1   Practice for Endocrinology, Regensburg, Germany
,
B. Schehler
1   Practice for Endocrinology, Regensburg, Germany
,
H. J. Schneider
2   Medizinische Klinik und Poliklinik IV, Ludwig-Maximilian-University, Munich, Germany
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 09. Juli 2012
first decision 13. September 2012

accepted 12. Oktober 2012

Publikationsdatum:
12. November 2012 (online)

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Abstract

Objective:

The efficacy of metformin for the treatment of obesity has been evaluated in few clinical trials with inconclusive results. Moreover, the effectiveness in a real-life outpatient setting has not been tested until today. In this study we aimed to examine the effectiveness of metformin as a weight reducing drug in obese and overweight patients with regard to their degree of insulin resistance.

Design and patients:

We treated 154 consecutive patients with a body mass index ≥27 kg/m2 in an outpatient setting over 6 months with metformin up to a dosage of 2 500 mg per day. Additionally, we included 45 untreated patients as controls. Patients were monitored for weight changes over 6 months. Before metformin treatment was started insulin sensitivity was determined in all patients by calculating HOMA index and Matsuda index after a 75 g oral glucose tolerance test.

Results:

The mean weight loss in the metformin treated group was 5.8±7.0 kg (5.6±6.5%). Untreated controls gained 0.8±3.5 kg (0.8±3.7%) on average. Patients with severe insulin resistance lost significantly more weight as compared to insulin sensitive patients. The percentage of weight loss was independent of age, sex or BMI.

Conclusion:

Metformin is an effective drug to reduce weight in a naturalistic outpatient setting in insulin sensitive and insulin resistant overweight and obese patients.

Key words

metformin - obesity - insulin resistance
 

  • References

  • 1 Li Z, Maglione M, Tu W et al. Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med 2005; 142: 532-546
    CrossrefPubMedSuche in Google Scholar
  • 2 Christopoulou FD, Kiortsis DN. An overview of the metabolic effects of rimonabant in randomized controlled trials: potential for other cannabinoid 1 receptor blockers in obesity. J Clin Pharm Ther 2011; 36: 10-18
    CrossrefPubMedSuche in Google Scholar
  • 3 Meneghini LF, Orozco-Beltran D, Khunti K et al. Weight beneficial treatments for type 2 diabetes. J Clin Endocrinol Metab 2011; 96: 3337-3353
    CrossrefPubMedSuche in Google Scholar
  • 4 Bennett WL, Odelola OA, Wilson LM et al. Evaluation of guideline recommendations on oral medications for type 2 diabetes mellitus: a systematic review. Ann Intern Med 2012; 156: 27-36
    CrossrefPubMedSuche in Google Scholar
  • 5 Sterne J. Pharmacology and mode of action of hypoglycaemic guanidine derivatives. In: Campbell GD. (ed.). Oral hypoglycaemic agents. London: Academic; 1969: 193-245
    Suche in Google Scholar
  • 6 Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997; 18: 774-800
    CrossrefPubMedSuche in Google Scholar
  • 7 Unlühizarci K, Keleştimur F, Bayram F et al. The effects of metformin on insulin resistance and ovarian steroidogenesis in women with polycystic ovary syndrome. Clin Endocrinol 1999; 51: 231-236
    CrossrefPubMedSuche in Google Scholar
  • 8 Lee A, Morley JE. Metformin decreases food consumption and induces weight loss in subjects with obesity with type II non-insulin-dependent diabetes. Obes Res 1998; 6: 47-53
    PubMedSuche in Google Scholar
  • 9 Stumvoll M, Nurjhan N, Perriello G et al. Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. N Engl J Med 1995; 333: 550-554
    CrossrefPubMedSuche in Google Scholar
  • 10 Lustig RH. Hypothalamic obesity: the sixth cranial endocrinopathy. The Endocrinologist 2002; 12: 210-217
    CrossrefPubMedSuche in Google Scholar
  • 11 Sigal RJ, El-Hashimy M, Martin BC et al. Acute post-challenge hyperinsulinemia predicts weight gain. Diabetes 1997; 46: 1025-1029
    CrossrefPubMedSuche in Google Scholar
  • 12 Odeleye OE, de Courten M, Pettitt DJ et al. Fasting hyperinsulinemia is a predictor of increased body weight gain and obesity in Pima Indian children. Diabetes 1997; 46: 1341-1345
    CrossrefPubMedSuche in Google Scholar
  • 13 Bailey DJ, Turner RC. Metformin. N Engl J Med 1996; 334: 574-579
    CrossrefPubMedSuche in Google Scholar
  • 14 Hermann LS, Melander A. Biguanides: basic aspects and clinical uses. In: Alberti KGMM, DeFronzo RA, Keen H, Zimmet P. (eds.). International textbook of diabetes mellitus. Vol. 1. Chichester, England: John Wiley; 1992: 773-795
    Suche in Google Scholar
  • 15 Knowler WC, Barrett-Connor E, Fowler SE et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393-403
    CrossrefPubMedSuche in Google Scholar
  • 16 Diabetes Prevention Program Research Group . Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care 2012; 35: 731-772
    CrossrefPubMedSuche in Google Scholar
  • 17 Fontbonne A, Diouf I, Baccara-Dinet M et al. Effects of 1-year treatment with metformin on metabolic and cardiovascular risk factors in non-diabetic upper-body obese subjects with mild glucose anomalies: a post-hoc analysis of the BIGPRO1 trial. Diabetes Metab 2009; 35: 385-391
    CrossrefPubMedSuche in Google Scholar
  • 18 Gambineri A, Patton L, Vaccina A et al. Treatment with flutamide, metformin, and their combination added to a hypocaloric diet in overweight-obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006; 91: 3970-3980
    CrossrefPubMedSuche in Google Scholar
  • 19 Derosa G, Maffioli P. Anti-obesity drugs: a review about their effects and their safety. Expert Opin Drug Saf 2012; 11: 459-471
    CrossrefPubMedSuche in Google Scholar
  • 20 Ara R, Blake L, Gray L et al. What is the clinical effectiveness and cost-effectiveness of using drugs in treating obese patients in primary care? A systematic review. Health Technol Assess 2012; 1: 1-195
    PubMedSuche in Google Scholar
  • 21 Bray GA, Ryan DH. Medical Therapy for the Patient with Obesity. Circulation 2012; 125: 1695-1703
    CrossrefPubMedSuche in Google Scholar
  • 22 Gillies CL, Abrams KR, Lambert PC et al. Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis. BMJ 2007; 334: 299-308
    CrossrefPubMedSuche in Google Scholar
  • 23 Setter SM, Iltz JL, Thams J et al. Metformin hydrochloride in the treatment of type 2 diabetes mellitus: a clinical review with a focus on dual therapy. Clin Ther 2003; 25: 2991-3026
    CrossrefPubMedSuche in Google Scholar
  • 24 Haffner S, Temprosa M, Crandall J et al. Intensive lifestyle intervention or metformin on inflammation and coagulation in participants with impaired glucose tolerance. Diabetes 2005; 54: 1566-1572
    CrossrefPubMedSuche in Google Scholar
  • 25 Wang M, Tong JH, Zhu G et al. Metformin for treatment of antipsychotic-induced weight gain: A randomized, placebo-controlled study. Schizophr Res 2012; 138: 54-57
    CrossrefPubMedSuche in Google Scholar
  • 26 Bushe CJ, Bradley AJ, Doshi S et al. Changes in weight and metabolic parameters during treatment with antipsychotics and metformin: do the data inform as to potential guideline development? A systematic review of clinical studies. Int J Clin Pract 2009; 63: 1743-1761
    CrossrefPubMedSuche in Google Scholar
  • 27 Park MH, Kinra S, Ward KJ et al. Metformin for obesity in children and adolescents: a systematic review. Diabetes Care 2009; 32: 1743-1745
    CrossrefPubMedSuche in Google Scholar
  • 28 Mauras N, DelGiorno C, Hossain J et al. Metformin use in children with obesity and normal glucose tolerance-effects on cardiovascular markers and intrahepatic fat. J Pediatr Endocrinol Metab 2012; 25: 33-40
    PubMedSuche in Google Scholar
  • 29 Metwally M, Amer S, Li TC et al. of metformin versus orlistat for the management of obese anovulatory women. Hum Reprod 2009; 24: 966-975
    PubMedSuche in Google Scholar
  • 30 Harborne LR, Sattar N, Norman JE et al. Metformin and weight loss in obese women with polycystic ovary syndrome: comparison of doses. J Clin Endocrinol Metab 2005; 90: 4593-4598
    CrossrefPubMedSuche in Google Scholar
  • 31 Ghandi S, Aflatoonian A, Tabibnejad N et al. The effects of metformin or orlistat on obese women with polycystic ovary syndrome: a prospective randomized open-label study. J Assist Reprod Genet 2011; 28: 591-596
    CrossrefPubMedSuche in Google Scholar
  • 32 Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999; 22: 1462-1470
    CrossrefPubMedSuche in Google Scholar
  • 33 Levri KM, Slaymaker E, Last A et al. Metformin as treatment for overweight and obese adults: a systematic review. Ann Fam Med 2005; 3: 457-461
    CrossrefPubMedSuche in Google Scholar
  • 34 Goodpaster BH, Kelley DE, Wing RR et al. Effects of weight loss on regional fat distribution and insulin sensitivity in obesity. Diabetes 1999; 48: 839-847
    CrossrefPubMedSuche in Google Scholar
  • 35 Glueck CJ, Fontaine RN, Wang P et al. Metformin reduces weight, centripetal obesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30. Metabolism 2001; 50: 856-861
    CrossrefPubMedSuche in Google Scholar
  • 36 Gokcel A, Gumurdulu Y, Karakose H et al. Evaluation of the safety and efficacy of sibutramine, orlistat and metformin in the treatment of obesity. Diabetes Obes Metab 2002; 4: 49-55
    CrossrefPubMedSuche in Google Scholar
  • 37 Mogul HR, Peterson SJ, Weinstein BI et al. Long-term (2–4 year) weight reduction with metformin plus carbohydrate-modified diet in euglycemic, hyperinsulinemic, midlife women (Syndrome W). Heart Dis 2003; 5: 384-392
    CrossrefPubMedSuche in Google Scholar
  • 38 Dohm GL, Tapscott E, Pories W et al. An in vitro human muscle preparation suitable for metabolic studies. Decreased insulin stimulation of glucose transport in muscle from morbidly obese and diabetic subjects. J Clin Invest 1988; 82: 486-494
    CrossrefPubMedSuche in Google Scholar
  • 39 Oppert JM, Nadeau A, Tremblay A et al. Plasma glucose, insulin, and glucagon before and after long-term overfeeding in identical twins. Metabolism 1995; 44: 96-105
    CrossrefPubMedSuche in Google Scholar
  • 40 Luyckx AS, Lefevbre PJ. Plasma insulin in reactive hypoglycemia. Diabetes 1971; 20: 435-442
    PubMedSuche in Google Scholar
  • 41 Schultes B, Oltmanns KM, Kern W et al. Modulation of hunger by plasma glucose and metformin. J Clin Endocrinol Metab 2003; 88: 1133-1141
    CrossrefPubMedSuche in Google Scholar
  • 42 Giannarelli R, Aragona M, Coppelli A et al. Reducing insulin resistance with metformin: the evidence today. Diabetes Metab 2003; 29: 28-35
    PubMedSuche in Google Scholar
  • 43 Mizuno TM, Funabashi T, Kleopoulos SP et al. Specific preservation of biosynthetic responses to insulin in adipose tissue may contribute to hyperleptinemia in insulin-resistant obese mice. J Nutr 2004; 134: 1045-1050
    PubMedSuche in Google Scholar
  • 44 Cusin I, Terrettaz J, Rohner-Jeanrenaud F et al. Hyperinsulinemia increases the amount of GLUT4 mRNA in white adipose tissue and decreases that of muscles: a clue for increased fat depot and insulin resistance. Endocrinology 1990; 127: 3246-3248
    CrossrefPubMedSuche in Google Scholar
  • 45 Tan S, Hahn S, Benson S et al. Metformin improves polycystic ovary syndrome symptoms irrespective of pre-treatment insulin resistance. Eur J Endocrinol 2007; 157: 669-676
    CrossrefPubMedSuche in Google Scholar
  • 46 Paolisso G, Amato L, Eccellente R et al. Effect of metformin on food intake in obese subjects. Eur J Clin Invest 1998; 28: 441-446
    CrossrefPubMedSuche in Google Scholar
  • 47 Mick GJ, Wang X, Ling Fu C et al. Inhibition of leptin secretion by insulin and metformin in cultured rat adipose tissue. Biochim Biophys Acta 2000; 1502: 426-432
    CrossrefPubMedSuche in Google Scholar
  • 48 Morin-Papunen LC, Koivunen RM, Tomas C et al. Decreased serum leptin concentrations during metformin therapy in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 1998; 83: 2566-2568
    CrossrefPubMedSuche in Google Scholar
  • 49 Mannucci E, Ognibene A, Cemasco F et al. Effect of metformin on glucagon-like peptide-1 (GLP-1) and leptin levels in obese nondiabetic subjects. Diabetes Care 2001; 24: 489-494
    CrossrefPubMedSuche in Google Scholar
  • 50 Mannucci E, Tesi F, Bardini G et al. Effects of metformin on glucagon-like peptide-1 levels in obese patients with and without Type 2 diabetes. Diabetes Nutr Metab 2004; 17: 336-342
    PubMedSuche in Google Scholar