Weight loss is perhaps the most important therapeutic intervention in obese patients with T2D. Weight loss intervenes in the underlying pathophysiology and restores insulin sensitivity and sometimes even insulin secretion. In addition, it improves dyslipidemia and hypertension. In contrast, most pharmacological interventions only relieve the symptoms of the complex disease process underlying T2D whilst the disease process itself is not addressed and even progresses in the course of time. Unfortunately, the effect of weight loss interventions such as diet and lifestyle or even drugs (orlistat, sibutramine) is often modest (3-5 kg) and short-lived.