Managing CMR

Preventing Type 2 Diabetes

Targeting Abdominal Obesity

Pharmacotherapy for the Prevention of Type 2 Diabetes

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Orlistat, a gastrointestinal lipase inhibitor, has been shown to decrease body weight in humans (18). In the XENDOS study (Xenical in the Prevention of Diabetes in Obese Subjects), Torgerson et al. (19) randomized 3,305 obese patients with or without IGT to a lifestyle intervention group, with either a placebo or orlistat 120 mg, three times daily. After the 4 year treatment period, the cumulative incidence of diabetes was 9.0% with placebo and 6.2% with orlistat, for an overall risk reduction of 37.3%. Orlistat was more effective than the placebo in decreasing body weight (5.8 vs. 3.0 kg) and waist circumference (6.4 vs. 4.4 cm). However, diabetes incidence only decreased in patients with IGT at baseline, even if body weight loss was similar in patients with and without IGT.

Thiazolidinediones (TZDs) are peroxisome-proliferator activated receptor-γ (PPAR-γ) agonists that have been shown to improve insulin sensitivity while increasing total body fat in patients with type 2 diabetes (20). Shadid and Jensen (21) tested the difference between diet and exercise and treatment with the PPAR-γ agonist pioglitazone in improving insulin sensitivity and body fat distribution in 39 abdominally obese, insulin-resistant, nondiabetic men and premenopausal women who were randomized to receive either 30 mg/day pioglitazone or a diet and exercise program for 20 weeks. They found that only the diet and exercise group had a reduction of waist circumference, body fat percentage, and intra-abdominal adipose tissue surface as calculated by computed tomography at the L4-L5 level. Similar improvements in insulin resistance markers and other cardiometabolic risk variables were observed in both groups, suggesting that diet and exercise improve insulin sensitivity by mobilizing intra-abdominal adipose tissue.

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18. Tonstad S, Pometta D, Erkelens DW, et al. The effect of the gastrointestinal lipase inhibitor, orlistat, on serum lipids and lipoproteins in patients with primary hyperlipidaemia. Eur J Clin Pharmacol 1994; 46: 405-10.
19. Torgerson JS, Hauptman J, Boldrin MN, et al. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 2004; 27: 155-61.
20. Kelly IE, Han TS, Walsh K, et al. Effects of a thiazolidinedione compound on body fat and fat distribution of patients with type 2 diabetes. Diabetes Care 1999; 22: 288-93.
21. Shadid S and Jensen MD. Effects of pioglitazone versus diet and exercise on metabolic health and fat distribution in upper body obesity. Diabetes Care 2003; 26: 3148-52.