Hormonal
Polygenic scores for BMI and Type 2 Diabetes do not significantly predict weight loss outcomes in patients treated with GLP-1 receptor agonists.
If you are taking a GLP-1 RA (like semaglutide or liraglutide), your common genetic risk for obesity does not predict how much weight you will lose. The drug's effectiveness is largely independent of your polygenic score for BMI or Type 2 Diabetes. Focus on adherence and lifestyle factors rather than genetic testing for treatment selection.
We found no significant associations between GLP1-RA-induced weight loss and polygenic scores for body mass index or type 2 diabetes, nor with missense variants in GLP1R.
Why this rating
Large multi-ancestry biobank study (n=6,750) with robust statistical power to detect small effects.
Source
Association between plausible genetic factors and weight loss from GLP1-RA and bariatric surgery
J German et al. · Nature Medicine · 2025
DOI 10.1038/s41591-025-03645-3
More from this paper
- GLP-1 RA treatment results in significantly lower weight loss in individuals of African and admixed American ancestry compared to European ancestry, after adjusting for baseline factors.Good
- A higher polygenic score for BMI is associated with lower weight loss following bariatric surgery, although the effect size is modest and attenuates in sensitivity analyses.Moderate
Related findings · Hormonal
- Initial treatment for type 2 diabetes should be a combination of metformin and either an SGLT-2 inhibitor or a GLP-1 receptor agonist to achieve cardiorenal protection, rather than monotherapy or older agents like sulfonylureas.Strong
- For patients with specific monogenic obesity syndromes (leptin deficiency, POMC/PCSK1/LEPR mutations), targeted pharmacotherapy (recombinant leptin or setmelanotide) is highly effective and should be prioritized, unlike in polygenic obesity.Strong
- Continued weekly administration of 2.4 mg subcutaneous semaglutide prevents weight regain and promotes further weight loss in adults with overweight or obesity, whereas switching to placebo results in significant weight regain.Strong
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