Sustained weight loss exceeding 100 kg with sequential incretin-based therapy in Prader–Willi syndrome

Yovera-Aldana M.; Manrique-Hurtado H.; Umpierrez G.E. · JCEM Case Reports (2026) · DOI: 10.1210/jcemcr/luag260

Resumen

Prader–Willi syndrome (PWS) is a neurogenetic disorder characterized by hyperphagia, severe obesity, and early-onset metabolic complications, in which durable weight loss is rarely achieved. We report a 29-year-old man with genetically confirmed maternal uniparental disomy PWS who presented with severe obesity (185 kg; body mass index [BMI] 59.7 kg/m2) and newly diagnosed type 2 diabetes (glycated hemoglobin [HbA1c], 8.3% [SI: 67 mmol/mol] [reference range, <5.7% (SI: <39 mmol/mol)]). He received sequential incretin-based therapy, initiated with retatrutide (1-12 mg weekly) within a clinical trial, followed by oral semaglutide and then dulaglutide after retatrutide became unavailable, together with a structured hypocaloric diet and supervised exercise. At 18 months, total weight loss reached 58.8% (−108.7 kg), with HbA1c of 4.9% (SI: 30 mmol/mol), consistent with diabetes remission after discontinuation of all glucose-lowering medications. Mild transient gastrointestinal symptoms occurred during dose escalation, with no serious adverse events. Follow-up bioimpedance showed a skeletal muscle mass of 38.5 kg after a 58.8% reduction in total body weight. © The Author(s) 2026. Published by Oxford University Press on behalf of the Endocrine Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. See the journal About page for additional terms.

Instituciones: Universidad Científica del Sur