Sustained weight loss exceeding 100 kg with sequential incretin-based therapy in Prader-Willi syndrome.
A 29-year-old man with Prader-Willi syndrome lost 108.7 kg over 18 months using sequential incretin-based therapy, but this is a single case report and results may not be generalizable.
Where it sits
this study against the rest of the retatrutide (ly3437943) corpusSummary and findings
A 29-year-old man with Prader-Willi syndrome and severe obesity underwent sequential incretin-based therapy, starting with retatrutide at doses of 1-12 mg weekly. After 18 months, he achieved a total weight loss of 108.7 kg and a reduction in HbA1c to 4.9%. Mild gastrointestinal symptoms were reported during dose escalation.
Abstract
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/m<sup>2</sup>) 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.
Background
Prader-Willi syndrome (PWS) is a neurogenetic disorder that leads to severe obesity and metabolic complications, making weight management challenging. Previous literature indicates that durable weight loss in PWS is rarely achieved. This study reports on a case where sequential incretin-based therapy was employed to address obesity and diabetes in a patient with genetically confirmed PWS.
Methods
The study describes a single case of a 29-year-old male with PWS who received sequential incretin-based therapy, starting with retatrutide at doses ranging from 1-12 mg weekly, followed by oral semaglutide and dulaglutide. The intervention lasted for 18 months and included a structured hypocaloric diet and supervised exercise. Primary outcomes included weight loss and changes in HbA1c levels.
Results
At 18 months, the patient achieved a total weight loss of 108.7 kg, which corresponds to a 58.8% reduction in body weight. The HbA1c level improved from 8.3% to 4.9%, indicating a potential remission of diabetes. No serious adverse events were reported, although mild transient gastrointestinal symptoms were noted during dose escalation.
Interpretation
The findings suggest that sequential incretin-based therapy may lead to significant weight loss and improved glycemic control in patients with PWS. However, the effect size observed in this single case may not be clinically meaningful across a broader population. Limitations include the lack of a control group and the potential for confounding factors due to the study's design.
Key findings
- Initial weight of 185 kg, BMI 59.7 kg/m².
- Total weight loss of 108.7 kg (58.8%) at 18 months.
- HbA1c decreased from 8.3% to 4.9% after treatment.
- Skeletal muscle mass measured at 38.5 kg after weight loss.
Limitations
- Single case report, n=1.
- No control group for comparison.
- Short follow-up duration of 18 months.
- Potential confounding factors not controlled.