From adiposity to multisystem morbidity: the case for weight loss as disease modification.

Large-scale randomized evidence shows weight loss from incretin-based therapies is a disease-modifying strategy in several obesity-related conditions, with average weight loss of about 14–20% in people without diabetes.

• Why it matters: Obesity is linked to multisystem morbidity, but the degree to which weight-loss interventions prevent or modify specific diseases varies and many conditions remain insufficiently studied.
• What they did: The Review triangulates evidence from epidemiology, genetic analyses (including Mendelian randomisation), observational weight-change studies, and randomized trials, emphasizing semaglutide and tirzepatide.
• The result: Robust trial support exists for disease modification in some conditions (including type 2 diabetes and heart failure with preserved ejection fraction), while musculoskeletal, respiratory, cardiovascular, and mental health disorders need more trials across disease stages and weight-loss magnitudes.

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