Orlistat Plus Metformin: An Effective Combination?

The most common ways of losing weight are dieting and increasing the amount of daily exercise. However, obese persons often want to lose weight more quickly than dieting will allow. Thus, anti-obesity drugs offer another avenue. Two antiobesity agents that have been used for patients with diabetes mellitus are orlistat (Xenical®) and metformin (Glucophage®).

Orlistat inhibits gastrointestinal lipase and thus reduces the absorption of dietary fat by about 30%. Generally, treatment with orlistat also significantly improves insulin sensitivity. Metformin, an antihyperglycemic agent, decreases hyperinsulinemia and insulin resistance, leading to decreased adiposity in obese persons and those with non-insulin-dependent diabetes mellitus.

Would teaming these two agents together improve weight loss due to their different mechanisms of action? Dr. R. Sari and colleagues at Akdeniz University School of Medicine, Antalya, Turkey, recently conducted a prospective randomized study of 57 obese women (BMIs >30 kg/m2) with normal glucose tolerance (Int J Obesity 2004;28:1059). All the women ate the same foods in the same amounts during the study: All consumed a diet of 1200 to 1600 kcal/day, representing a deficiency of approximately 600 to 850 kcal/day. Approximately 50% of calories came from carbohydrate, 20% from protein, and 30% from fat.

After one month of dietary therapy, each woman was randomly assigned to receive either 120 mg orlistat, three times a day, or orlistat, 120 mg twice daily, plus 850 mg metformin twice daily. All the women took the medications for 3 months. Body weight and insulin resistance were measured at baseline, after the first month, and after the fourth month.

No real benefit came from the combination

Body weight, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglyceride levels were similar in both groups at baseline, and after the first and fourth months. There was no statistically significant change in serum lipid levels during the study in either group.

Both agents were effective for weight loss and for reducing insulin resistance. The mean weight loss in groups 1 and 2 was 2.9 lb and 2.4 lb, respectively, from baseline to the first month, and 10.5 lb and 12.7 lb, respectively, from the first to the fourth month. Adding metformin did not result in a significant additional effect on weight loss and insulin resistance when compared to orlistat alone.