Liraglutide Shows Promise for Weight Loss in People with Rare Genetic Forms of Obesity | Research

The takeaway

In a real-world cohort of adults with molecularly confirmed or suspected genetic obesity, liraglutide 3 mg produced clinically meaningful weight loss of ~5% with improvements in appetite, body composition, and metabolic markers.

~5% weight loss in 12 weeks
Liraglutide achieved clinically meaningful weight loss in adults with genetic obesity — a population where lifestyle interventions typically fail

What the researchers found

Liraglutide 3 mg produced median weight loss of 4.7% (MCGO) and 5.2% (HSGO) after 12 weeks at maximum dose, with significant improvements in appetite, fat mass, fasting glucose, and HbA1c in adults with genetic obesity.

Why it matters

People with genetic obesity have few effective treatment options — lifestyle interventions that work for common obesity often fail for them. Showing that GLP-1 drugs like liraglutide are effective in this population could transform care for thousands of people with rare genetic conditions driving severe obesity.

The numbers in context

The study included adults with molecularly confirmed genetic obesity (MCGO) and highly suspected genetic obesity (HSGO), tracked at a specialized center.

How the study worked

Real-world cohort study at Erasmus University Obesity Center, Rotterdam (March 2019–August 2023). 98 adults with molecularly confirmed (n=23) or suspected (n=75) genetic obesity received liraglutide 3 mg or naltrexone-bupropion per manufacturer protocol. Evaluation at 12 weeks on maximum/highest-tolerated dose assessed anthropometrics, body composition, metabolic markers, appetite, eating behavior, and quality of life.

Who was studied

Adults with molecularly confirmed or suspected genetic obesity

What this study cannot tell us

Real-world study without placebo control — can't definitively attribute all weight loss to medication. Short-term evaluation (12 weeks) doesn't address long-term efficacy or weight regain. The HSGO group lacked molecular confirmation, so some may not have true genetic obesity. Relatively small sample, especially the MCGO group (n=23).

How to read the evidence

Moderate evidence from a real-world cohort study at a specialized obesity center. The lack of placebo control and short follow-up limit conclusions, but the real-world setting adds practical relevance.

When this study was published

Published in 2024, reflecting current clinical practice for pharmacotherapy in genetic obesity at a leading European obesity center.

The bigger picture

Genetic obesity affects a small but significant population — possibly 5-10% of severe early-onset obesity cases have identifiable genetic causes. As genetic testing becomes more common, more patients will be diagnosed. This study suggests GLP-1 drugs remain effective even when obesity has a genetic basis, broadening the population that can benefit from these medications.

Questions still open

Would newer GLP-1 agonists like semaglutide produce even greater weight loss in genetic obesity?
Do specific genetic mutations predict better or worse response to GLP-1 therapy?
Is the weight loss sustained beyond the 12-week evaluation period?

Common questions

What is genetic obesity and how is it different from common obesity?

Genetic obesity is caused by specific mutations in genes that control hunger, satiety, or energy metabolism — often in the leptin-melanocortin pathway. People with genetic obesity typically develop severe obesity in early childhood and experience intense, uncontrollable hunger that lifestyle changes can't fix. It's estimated to account for 5-10% of severe early-onset obesity cases, though many cases remain undiagnosed.

Does this mean GLP-1 drugs work even if obesity is caused by genetics?

This study suggests yes — at least for short-term weight loss. Liraglutide produced about 5% weight loss in 12 weeks regardless of whether patients had molecularly confirmed or suspected genetic obesity. This is encouraging because it means GLP-1 drugs may work through pathways that aren't blocked by the specific genetic mutations causing the obesity, offering hope for a treatment-resistant population.

Read the original research

Treatment with liraglutide or naltrexone-bupropion in patients with genetic obesity: a real-world study.

EClinicalMedicine, 74, 102709

View on PubMed ↗Publisher’s paper ↗

Citation

Welling, Mila S; de Groot, Cornelis J; Mohseni, Mostafa; Meeusen, Renate E H; Boon, Mariëtte R; van Haelst, Mieke M; van den Akker, Erica L T; van Rossum, Elisabeth F C. (2024). Treatment with liraglutide or naltrexone-bupropion in patients with genetic obesity: a real-world study.. EClinicalMedicine, 74, 102709. https://doi.org/10.1016/j.eclinm.2024.102709