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This combination therapy consists of metformin, orlistat, and topiramate, and was evaluated by the University of Iowa in the REVIVE clinical trial. Metformin is a biguanide that improves insulin sensitivity and reduces hepatic glucose production, primarily through the activation of AMP-activated protein kinase (AMPK). Orlistat is a potent, specific, and long-acting inhibitor of gastric and pancreatic lipases, which prevents the absorption of dietary fats in the gastrointestinal tract. Topiramate is a sulfamate-substituted monosaccharide with anticonvulsant properties that contributes to weight loss through multiple mechanisms, including the modulation of GABAergic transmission and inhibition of carbonic anhydrase. The combination is designed to address obesity and metabolic syndrome X by targeting multiple physiological pathways involved in energy balance and metabolic health, with a specific clinical focus on reversing visceral obesity and improving vascular function.
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