Antiobesity pharmacotherapy in the management of Type 2 diabetes

Obesity is a well-known risk factor for the development of Type 2 diabetes mellitus. The management of the obese diabetic patient remains a challenge for the clinician but, in any case, weight reduction should be considered a s a key objective. In this respect, several antiobesity drugs have demonstr ated potential. However, while fenfluramine and dexfenfluramine have been s hown to promote weight loss and to directly improve insulin sensitivity, be ing two mechanisms contributing to better blood glucose control in obese Ty pe 2 diabetic patients, they were recently withdrawn due to safety problems . Sibutramine, a new selective norepinephrine and serotonin reuptake inhibi tor, promotes weight loss by decreasing food intake, an effect which leads to a mild improvement (significant in patients losing greater than or equal to 5% of initial body weight) of blood glucose control in obese diabetic p atients. Similarly, orlistat, a selective gastrointestinal lipase inhibitor which increases faecal fat losses, enhances diet-induced weight reduction and improves both blood glucose control and vascular risk profile, especial ly dyslipidaemia, in obese Type 2 diabetic patients. Further studies are re quired to better identify good responders to pharmacotherapy and specify th e role of antiobesity agents in the overall long-term management of obese s ubjects with Type 2 diabetes. Other novel pharmacological approaches deserv e further consideration, for instance beta-3 agonists aiming to increase en ergy expenditure, drugs interfering with tumor necrosis factor-alpha (TNF-a lpha) or free fatty acid release by the adipose tissue or agents that slow gastric emptying. However, until now, results regarding efficacy and/or saf ety have been disappointing or preliminary in humans. Copyright (C) 2000 Jo hn Wiley & Sons, Ltd.