Managing Cardiometabolic Risk

Pharmacotherapy for the prevention of type 2 diabetes

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Although the pharmacological arsenal to decrease body weight and intra-abdominal adipose tissue remains limited, a few pharmacological compounds have been shown to reduce atherogenic intra-abdominal fat. For example, rimonabant, a selective cannabinoid receptor-1 (CB1) blocker, has been shown to reduce food intake in both rodents and humans (15, 16). For the RIO-Diabetes trial, Scheen et al. (17) randomized 692 patients to rimonabant 5 mg/day, rimonabant 20 mg/day, or a placebo and followed these patients for a year. They reported that patients treated with rimonabant 20 mg/day decreased their body weight by 5.3 ± 5.2 kg and their waist circumference by 5.2 ± 6.1 cm. Patients treated with rimonabant 20 mg/day also had increased HDL cholesterol levels as well as decreased triglyceride, C-reactive protein, and HbA1C levels. The changes in HbA1C levels were directly associated with body weight loss. Further studies are required to do the following: 1) evaluate rimonabant’s ability to prevent diabetes rather than treat diabetes and its metabolic complications and 2) investigate whether rimonabant can reduce intra-abdominal adipose tissue as assessed using imaging techniques.

In the SERENADE trial, rimonabant’s ability to lower HbA1C was tested in 278 newly diagnosed diabetic patients (138 patients were treated with rimonabant and 140 patients with placebo). Compared to the placebo, rimonabant treatment produced a 0.5% greater reduction in HbA1C. The results of the SERENADE trial were very similar to those of RIO-Diabetes in terms of weight reduction, waist circumference, and improvements to HDL cholesterol and triglyceride levels.

Reference

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15. Thornton-Jones ZD, Kennett GA, Benwell KR, et al. The cannabinoid CB1 receptor inverse agonist, rimonabant, modifies body weight and adiponectin function in diet-induced obese rats as a consequence of reduced food intake. Pharmacol Biochem Behav 2006; 84: 353-9.

16. Després JP, Golay A and Sjostrom L. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 2005; 353: 2121-34.

17. Scheen AJ, Finer N, Hollander P, et al. Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet 2006.

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