{"id":108182,"date":"2026-04-15T15:05:51","date_gmt":"2026-04-15T18:05:51","guid":{"rendered":"https:\/\/ubirataonline.com.br\/some-people-dont-lose-weight-with-glp-1s-evidence-is-building-that-the-drugs-are-helping-anyway\/"},"modified":"2026-04-15T15:05:54","modified_gmt":"2026-04-15T18:05:54","slug":"some-people-dont-lose-weight-with-glp-1s-evidence-is-building-that-the-drugs-are-helping-anyway","status":"publish","type":"post","link":"https:\/\/ubirataonline.com.br\/en\/some-people-dont-lose-weight-with-glp-1s-evidence-is-building-that-the-drugs-are-helping-anyway\/","title":{"rendered":"Some people don\u2019t lose weight with GLP-1s. Evidence is building that the drugs are helping anyway"},"content":{"rendered":"


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\n For the majority of people who start using GLP-1 medicines with the hope of losing weight, the drugs can feel almost miraculous: Cravings are quieted. Exercise can become easier and more fun. Pounds that stubbornly remained for years finally dissipate.\n <\/p>\n

\n But for a smaller subset of people, the medicines don\u2019t help with weight loss. Clinical trials suggest that about 10% to 15% of people who try GLP-1s, such as Wegovy and Zepbound, are \u201cnon-responders\u201d when it comes to substantial weight loss. A study<\/a> published last week suggested that genetics may play a role.\n <\/p>\n

\n But research, including new findings published Tuesday, is also continuing to paint a picture of GLP-1 medicines\u2019 benefits independent of weight loss. Clinical trials in heart health<\/a>, for example, have suggested that the medicines can reduce the risk of heart attacks and strokes, and improve outcomes in heart failure<\/a>, even when participants don\u2019t lose weight \u2013 or, in some cases, possibly even if participants gain<\/em> weight.\n <\/p>\n

\n The latest findings shed light on how the drugs may improve liver health. Wegovy, made by Novo Nordisk and based on the active ingredient semaglutide, was approved<\/a> by the US Food and Drug Administration in August for a serious liver disease called metabolic dysfunction-associated steatohepatitis, or MASH, estimated to affect about 6% of US adults. The drug was shown<\/a> in a clinical trial to help dramatically improve markers of the disease.\n <\/p>\n

\n \u201cFor the most part, I think the dogma is that this improvement is driven by weight loss,\u201d said Dr. Daniel Drucker<\/a>, a pioneer of GLP-1 research at the University of Toronto whose lab produced the new study. \u201cBut we have seen hints in our lab that weight loss isn\u2019t the whole story.\u201d\n <\/p>\n

\n Drucker argues that the mounting evidence should change the way health insurers and government programs consider whether to pay for the medicines: Instead of assessing weight loss as a measure of their success, they should take into account their other benefits \u201cacross a wide range of very serious diseases.\u201d\n <\/p>\n

\n \u201cInsurance companies have historically required at least 5% weight loss after three to four months of treatment in order to continue covering GLP-1 treatment,\u201d said Dr. Jody Dushay<\/a>, who prescribes the medicines in her practice at Beth Israel Deaconess Medical Center in Boston. \u201cWith new information about metabolic benefits separate from weight loss, this will definitely need to be reconsidered.\u201d\n <\/p>\n

\n She estimates that about 5% to 8% of patients in her practice are what she calls \u201cweight non-responders\u201d to GLP-1s. The drugs are so named for the hormone they mimic, which plays a role in insulin secretion, stomach emptying and appetite.\n <\/p>\n

\n \u201cBut with the increasing number of indications for these medications,\u201d Dushay told CNN in an email, \u201cwe are going to see (or, we need to look for!) benefits in people who do not meet weight loss \u2018responder\u2019 criteria.\u201d\n <\/p>\n

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\n <\/source><\/source><\/source><\/source><\/source><\/picture>\n <\/div>\n<\/div>\n

\n Drucker\u2019s study, led by postdoctoral fellow Dr. Maria Gonzalez-Rellan, sought to understand why semaglutide appeared to improve markers of MASH regardless of whether participants lost weight in clinical trials.\n <\/p>\n

\n The research team did this, in part, by creating essentially \u201cweight non-responders\u201d out of lab mice, eliminating GLP-1 receptors in the brain in a group of them to make it so they don\u2019t lose weight with GLP-1 medicines, Drucker said.\n <\/p>\n

\n \u201cThat allows us to then say, \u2018OK, if we prevent weight loss, because that\u2019s mediated by the brain, do we still see the benefits of GLP-1 and improving liver health?\u2019 \u201d he explained. \u201cAnd the answer is: Absolutely, we see substantial benefits, even in the absence of weight loss.\u201d\n <\/p>\n

\n The team identified a group of cells in the liver that, when stimulated by GLP-1, kick-start a process that communicates with the immune system to \u201cquiet down inflammation,\u201d Drucker said. \u201cIt\u2019s this very rare population of blood vessel cells that\u2019s driving the reduction of inflammation.\u201d\n <\/p>\n

\n To further validate their findings, the group studied what happened when mice engineered to lack GLP-1 receptors in those liver cells lost a substantial amount of weight: no liver improvement.\n <\/p>\n

\n \u201cIt\u2019s elegant work,\u201d said Dr. Harlan Krumholz<\/a>, a cardiologist and professor at Yale School of Medicine who wasn\u2019t involved in the study.\n <\/p>\n

\n He pointed out, though, that since the study was done in mice, it can\u2019t be said with certainty that the same mechanisms are at play in people.\n <\/p>\n

\n \u201cBut we can now say that this is a biologically plausible explanation for why some benefits of these drugs appear to extend beyond simple weight reduction,\u201d Krumholz added.\n <\/p>\n

\n The ability of GLP-1 medicines to tamp down inflammation may be a key reason they help with heart conditions and kidney disease<\/a> in ways independent of weight loss, as well.\n <\/p>\n

\n A study of results from a major cardiovascular outcomes trial of Wegovy in 2024 found that its ability to reduce the risk of people having a second heart attack or stroke wasn\u2019t dependent on how much weight people lost.\n <\/p>\n

\n The study author, Professor John Deanfield<\/a> from University College London, suggested<\/a> that \u201cpositive impacts on blood sugar, blood pressure, or inflammation, as well as direct effects on the heart muscle and blood vessels,\u201d may be at play.\n <\/p>\n

\n That\u2019s not to say weight loss doesn\u2019t also help \u2013 and is probably a key driver of improvement in conditions including arthritis and sleep apnea, said Drucker, who has received consulting and speaking fees from companies that make GLP-1 medicines.\n <\/p>\n

\n But the new findings add to the body of evidence suggesting that the medicines could be used in more tailored ways, taking into account their sometimes substantial costs and side effects, which can include nausea and other gastrointestinal symptoms.\n <\/p>\n

\n \u201cIt\u2019s very important to understand: Should we be trying to maximize the weight loss, and sometimes that means using the highest doses of the medicine, and sometimes that means more side effects?\u201d Drucker said. \u201cOr, in this case with metabolic liver disease, we could only use a smaller dose of the medicine and not have so much of the adverse events, and it wouldn\u2019t cost the patient as much money because they\u2019re not taking as much of the drug.\n <\/p>\n

\n \u201cSo,\u201d Drucker added, \u201cit\u2019s really clinically relevant to understand how these medicines work in every one of these conditions.\u201d\n <\/p>\n<\/p><\/div>\n


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For the majority of people who start using GLP-1 medicines with the hope of losing weight, the drugs can feel almost miraculous: Cravings are quieted. Exercise can become easier and more fun. Pounds that stubbornly remained for years finally dissipate. But for a smaller subset of people, the medicines don\u2019t help with weight loss. 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