GLP-1s don't work for everyone: why and what options are being studied

About 12% of U.S. adults are taking GLP-1 medications, but studies estimate up to 20% of users may not respond; researchers report genetics and other factors can influence response, and a review notes combining GLP-1s with a naltrexone‑bupropion medication is being explored for some non-responders.

Many adults in the United States are using GLP-1 medications for weight loss or chronic conditions, and past trials generally show 5% to 15% weight loss over one year for people who respond. Recent research indicates that a notable minority—reported as up to 20%—may not respond to GLP-1 treatment, and a study in Nature suggests genetic differences can affect how well the drugs work. A separate review in Obesity Science and Practice examines combining GLP-1s with a fixed‑dose naltrexone‑bupropion medication (NB‑ER, sold as Contrave in some markets) as one possible approach for those with suboptimal response, and clinicians quoted in the article describe obesity as multifactorial and variable in treatment response. Key points: - About 12% of U.S. adults are reported to be taking a GLP-1 medication for weight loss or other chronic conditions. - Clinical trials commonly show average weight loss of roughly 5%–15% of starting body weight over one year for people who respond. - Up to 20% of users may have a poor or limited response; a Nature study reports genetic factors may influence response rates. - A review in Obesity Science and Practice discusses combining GLP-1s with naltrexone‑bupropion (NB‑ER/Contrave) to target both hunger and food cravings; the article notes further research and clinical evaluation are needed. Summary: A portion of people taking GLP-1 medications do not achieve expected weight-loss results, and emerging studies point to genetic and other biological factors as contributors. Researchers and clinicians are examining combined medication approaches and further research to better understand and address variable treatment responses; the timeline and broader clinical adoption remain under evaluation.