Pharmacotherapy for Weight Management and Prevention of Diabetes

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Weight reduction for the prevention of cardiovascular disease is an imperative in the current environment of epidemic obesity and metabolic syndrome. However, the failure rate is 70-95% within 1-2 years of weight loss. Weight loss is followed by a number of adaptations including decreased thyroid and immune function and changes in signaling in the central nervous system that result in weight regain. Thus, the treatment of obesity, which is the common denominator underlying the variable symptoms of the metabolic syndrome, remains a challenge in cardiovascular rehabilitation and prevention. Programs should emphasize a moderate weight loss of 5-10% that is achievable by lifestyle change, rather than dieting, and that is maintainable over time. Drugs may assist with this goal,but no studies that demonstrate a reduction in cardiovascular morbidity or mortality as a result of drug-assisted weight reduction have been done. Promisingly, treatment with a number of drugs may reduce the incidence of type 2 diabetes. This is important in light of the high risk of fatal and nonfatal macrovascular events in patients with type 2 diabetes.

Orlistat and sibutramine are two pharma-cotherapeutic options to assist weight reduction and prevent weight regain. Orlistat is a lipase inhibitor, causing partial malabsorption of dietary fat. The XENDOS study showed that the additional weight loss induced by orlistat compared to placebo, though small, reduced the development of type 2 diabetes by 37% in a large group of obese patients treated for 4 years.76 The attrition rate in this trial was 57%, which is similar to that observed in most large-scale obesity trials, but limits the representativeness of the results. Sibu-tramine induces weight loss by inhibiting the neuronal reuptake of norepinephrine and serotonin at the receptor sites that affect food intake, and preventing the decline in energy expenditure during weight loss. The SCOUT study is currently examining the effect of sibutramine on cardiovascular morbidity and mortality.77 Recently rimonabant, a selective cannabinoid-1 receptor blocker, was approved for the treatment of overweight and obesity. Studies have shown that combined with lifestyle intervention, a dose of 20 mg of rimonabant effectively reduces body weight and waist circumference and improves some cardiovascular risk factors.78

A number of other drug classes have been studied in regard to preventing type 2 diabetes. These include oral antidiabetic agents (met-formin, acarbose, sulfonylureas, and thiazoli-dinediones), antihypertensive drugs, and lipid-lowering drugs. Of these only oral antidia-betic drugs have been studied in randomized controlled clinical trials with the incidence of diabetes as the primary endpoint. Decreases in diabetes incidence have been shown with met-formin, acarbose, and troglitazone; however, it is unknown whether these drugs prevent or only delay the onset of diabetes.79 Studies of the effect of antihypertensive and lipid-lowering drugs on diabetes incidence have all been post-hoc analyses of trials with other primary endpoints; however, several ongoing trials will be able to provide more evidence on the pharmacological prevention of type 2 diabetes.79

Finally, it must be noted that metformin and pioglitazone are two oral antidiabetic drugs that may reduce cardiovascular events in patients with type 2 diabetes.80,81

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