When to Add GLP-1 Receptor Agonists to Metreleptin in Lipodystrophy, With Lindsay Fourman, MD

"If a patient is on metreleptin and you're looking to add another agent, a GLP-1 receptor agonist might be a good option,” Lindsay Fourman, MD, endocrinologist at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, told HCPLive.

The comments come alongside new real-world data presented at Endocrine Society (ENDO) Annual Meeting 2026, showing that nearly 1 in 5 adults receiving sustained metreleptin therapy for lipodystrophy subsequently initiated sustained GLP-1 receptor agonist therapy. While the descriptive analysis did not assess efficacy, it highlights growing clinical adoption of the combination and the need for prospective studies.

Metreleptin is approved by the US Food and Drug Administration (FDA) as leptin replacement therapy for complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy.

Since lipodystrophy is associated with severe insulin resistance, diabetes, hypertriglyceridemia, and ectopic fat accumulation, investigators have begun exploring GLP-1 receptor agonists as adjunctive therapy. Early retrospective and preclinical data suggest these agents may improve metabolic outcomes, supporting interest in combination treatment with metreleptin, although the available evidence remains limited and largely observational.

While the rationale for combination therapy includes potential metabolic benefits, clinicians should consider patients’ baseline health status, including pancreatitis risk and elevated triglyceride levels.

“In terms of who you'd hesitate with, there is this kind of cloud around the question of pancreatitis. A lot of data speaks against it now, so we're not so worried about pancreatitis with GLP-1s, but it is a little bit of a hesitation. If a patient just had pancreatitis, I would give it some time for resolution of that episode before starting. I might wait 6 months or something. I also try to get triglycerides down because that can be the trigger for pancreatitis.”

Once a GLP-1 receptor agonist has been initiated in a patient receiving metreleptin therapy, Fourman emphasized the importance of ongoing monitoring. Since metreleptin has been associated with hypoglycemia, blood glucose should be closely tracked, and she recommended the use of a continuous glucose monitor during titration for safety.

Ultimately, Fourman noted that case series suggest GLP-1 receptor agonist monotherapy in lipodystrophy may reduce HbA1c by about 1 to 2%, while combination therapy with metreleptin has been associated with reductions of 2 to 3% or greater in some cases, suggesting a response that may be more synergistic than simply additive. However, she emphasized that additional data are needed before the combination can be incorporated into routine clinical practice.

Editor’s Note: Fourman reports relevant disclosures with Theratechnologies, Chiesi Farmaceutici, and Rhythm Pharmaceuticals.

References

1. Fourman T, Berria R, Zadeh E, et al. Real-World Prescribing Patterns of Combined Metreleptin and GLP-1 Receptor Agonist Therapy in Adults with Lipodystrophy. Poster presented at: Endocrine Society; June 13-17, 2026; Chicago, Ill.

2. Lebenthal Y, Halperin S, Interator H, Brener A, Brown R. American Diabetes Association. Published March 19, 2025. Accessed June 26, 2026. https://diabetesjournals.org/care/article/48/5/e71/158022/Oral-Glucagon-Like-Peptide-1-Analog-as-an-Adjuvant