Popular weight-loss drugs GLP-1 generally work well for people living with HIV, and they can improve heart, liver and gut health and reduce smoking in line with their known benefits for obesity and diabetes, according to studies presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2026). However, much remains to be learned about their long-term use in this population.
“With the exception of antiretroviral therapy, I can’t think of another class of medicine where there are so many voices,” said Todd Brown, MD, PhD, of Johns Hopkins Medicine, during his plenary talk. GLP-1 Agonists: Are They a Cure for Everything? He concluded that interest is warranted, but there are unanswered questions for people with HIV, and “global access will be a major challenge.”
Weight gain and metabolic disorders are an increasing concern for HIV patients with age. Glucagon-like peptide-1 (GLP-1) receptor agonists, including semaglutide (Ozempac or Vigovi), mimic a natural hormone that suppresses appetite, regulates insulin and blood sugar, and slows gastric emptying. Tirzepatide (Mounjaro or Zepbound) targets both GLP-1 and another gut hormone called GIP. Originally developed to treat type 2 diabetes, these drugs are now widely used to manage obesity. They have been shown to reduce the risk of heart and kidney disease and some types of cancer, and to improve sleep apnea and arthritis pain, and are currently being studied for fatty liver disease, addiction and other conditions.
Real world use
Three studies at CROI looked at the real-world use of GLP-1 agonists in people living with HIV.
Lauren O’Connor, George Washington University Milken Institute School of Public Health, PhD, MPH, and colleagues evaluated outcomes in the DC Cohort Longitudinal Status Neutral Study of 362 HIV-positive people who took GLP-1 medication for at least six months. Most had diabetes (82%) or obesity (78%). The most commonly used GLP-1 was semaglutide (50%). The average time on medication was 3.2 years, but 71% had a gap of more than three months between their prescriptions.
Nearly one in five participants (19%) lost between 5% and 10% of their baseline body weight, and 11% lost 10% or more, but this remained two-thirds of the 5% weight loss threshold. Black people appeared to lose less weight than white people, but the difference was not statistically significant after adjusting for other factors. People with diabetes are at least 10% more likely to experience weight loss than people with only obesity, this is also the case for HIV-negative people. Age and CD4 T-cell count did not differ between weight loss categories.
Daniel Lee, MD, of the University of California, San Diego, and colleagues specifically looked at the use of terzapatide, which produces more weight loss than semaglutide in the general population. In this analysis of 61 people with HIV, the overall weight loss was about 14% of baseline body weight over 12 months – slightly less than the 17% loss seen in the larger population. Here, too, people with diabetes only lost less weight than obese/overweight people (22 vs. 37 pounds, respectively). Participants also saw significant reductions in hemoglobin A1C (a measure of blood sugar) and blood pressure, improved HDL cholesterol levels and a 10-year reduction in heart disease risk. However, more than a quarter (26%) stopped taking terzapatide before completing one year, mostly because of side effects or insurance issues.
Heidi Crane, MD, MPH, of the University of Washington in Seattle, and colleagues compared the use of semaglutide versus terzapatide at the AIDS Research Network’s Center for Integrated Clinical Systems (CNICS), which follows HIV-positive adults in US academics. Three-quarters were male, and the median age was approximately 52 years. About 80% were obese and half had diabetes. A total of 2,187 people started semaglutide between April 2018 and July 2025, but only 497 people started terzepatide, which was not approved until 2022. Although the percentage of weight loss in this study was lower than in the previous two, those who used terzapatide lost more weight and improved their A1C levels more than semaglutide.
Special conditions
Crane’s team also looked at changes in smoking among people who received semaglutide in the CNICS group. In this analysis, 204 people with HIV reported smoking when they started semaglutide for diabetes or weight management, an average of 10.5 cigarettes per day. After starting the drug, smoking decreased to 2.7 cigarettes per day – a 26% reduction. “Semiglutide may provide additional benefits to overall health in HIV-infected individuals,” the researchers concluded.
In another CNICS analysis, Lara Hyder, PharmD, University of Manitoba, Canada, and colleagues evaluated the effect of semaglutide on depression in HIV-infected people. Although some early reports suggested that GLP-1 agonists may be associated with an increased risk of suicide, extensive research by the Food and Drug Administration found no such link—and, in fact, some studies found a reduced risk. Reassuringly, Haider’s study, which included 354 HIV-positive people who started semaglutide, found that the drug was not associated with an overall worsening of depressive symptoms with absent, mild, moderate, or severe depression at baseline.
Looking back at the CNICS cohort, Jamie Ma, MD, University of Washington, and colleagues evaluated the association between semaglutide use and liver fibrosis. Metabolic disorder-associated steatohepatitis (MASLD) and its more severe form, metabolic disorder-associated steatohepatitis (MASH), are a growing concern for HIV patients. Over time, the buildup of fat in the liver leads to inflammation, fibrosis (liver scarring), cirrhosis, and liver cancer. Based on a study of HIV-negative people, the Food and Drug Administration last year approved Vigovi to treat MASH in people with moderate to advanced fibrosis.
This analysis included 1,850 people living with HIV who started semaglutide for diabetes or weight loss and data available to calculate the FIB-4 liver fibrosis score (age, platelet count and ALT and AST liver enzyme levels). About three-quarters were men, the median age was 52 years, most had an undetectable HIV load, and the average CD4 count was about 800. Based on FIB-4 scores, 74% were absent with mild fibrosis, 23% had moderate fibrosis and 3% had advanced fibrosis.
Semaglutide was associated with a reduction in FIB-4 fibrosis scores in participants with mild to advanced liver stiffness, with the greatest improvement seen in those with severe fibrosis. “Our findings, together with previous studies, suggest that semaglutide may play a role in the management of MASLD and liver fibrosis in people with HIV, particularly as they age and experience the long-term effects of cardiometabolic disease,” the researchers concluded.
While the above studies were observational, Allison Ross Eckard, MD, of the Medical University of South Carolina, and colleagues reported new findings in a randomized controlled trial of semaglutide versus placebo in people with HIV, focusing on subclinical heart health. This trial enrolled 108 non-diabetic people with viral suppression on stable antiretroviral therapy who had lipohypertrophy or central fat accumulation. About 60% were men, and the average age was 53 years.
Researchers previously reported that participants assigned to semaglutide showed improvements in weight, total body fat, visceral fat, blood pressure, glucose metabolism and lipid levels over 32 weeks compared to those taking placebo. In the current analysis, they found “no significant effects” on markers of subclinical vascular disease (including endothelial function and arterial stiffness) or calcified atherosclerotic plaque. However, they did see “improvements in overall cardiometabolic health and heart disease risk,” including significant reductions in C-reactive protein (a biomarker of inflammation), significant reductions in 10-year heart disease risk and a trend toward better oxygen consumption.
Finally, Miguel Marin, PhD, of the African Health Research Institute, and colleagues observed changes in gut health in a subset of participants in the LIROH (liraglutide for obesity in HIV) trial in South Africa. HIV is known to disrupt intestinal homeostasis and integrity of the intestinal epithelial lining, contributing to chronic immune dysfunction and inflammation despite viral suppression with antiretroviral therapy. Liraglutide (Victoza or Saxenda) is an older GLP-1 agonist that is injected once daily, while semaglutide and terzapatide are once-weekly injections.
The researchers collected blood samples and colon biopsies of colon and duodenal tissue from the five test participants at four time points. As expected, liraglutide reduced weight loss and A1C levels. Biopsy samples showed favorable changes in intestinal T cells and epithelial cells after initiation of liraglutide, while blood samples showed reductions in various inflammatory biomarkers. Based on these findings, the researchers suggested that GLP-1 receptor agonists may be “a potential strategy for reducing intestinal pathology in HIV patients.”
Hopes and Obstacles
These studies represent only the tip of the iceberg when it comes to research on GLP-1 drugs for people living with HIV. At last year’s CROI, researchers reported data showing that semaglutide can slow biological aging, improve cognitive function and gut health and reduce alcohol use in people living with HIV.
Reviewing the body of evidence to date, Brown noted that the drug significantly improves inflammation even before people lose a lot of weight, possibly due to a direct effect on T cells. Their known ability to reduce the “food noise” can lead to other cravings and addictions. They are even being explored as longevity medicines.
But the remaining questions remain. People on GLP-1 agonists typically lose less body weight in addition to fat, but it is still unclear whether this is due to muscle loss or bone loss leading to decreased performance. Weight loss is reversible when the drug is stopped, and little is known about maintenance strategies, such as lower doses or less frequent dosing. Important clinical trials included fewer participants than 75, so more research is needed on outcomes as people age. Are the risks and benefits of these drugs different in people with HIV than in people without HIV? Can drugs reduce the chronic inflammation and immune dysfunction seen in people with HIV, and if so, how will they affect common comorbid conditions?
Brown noted that it is estimated that 27% of the world’s population is eligible for GLP-1 drugs and that with universal access we could reduce global obesity by 20% and save 28 million lives over a five-year period. The World Health Organization recently published guidelines stating that GLP-1 therapy may be used as a treatment for obesity.
“The challenge, of course, is getting these drugs to the people who need them,” Brown said. “Here we come to the real Achilles heel of this treatment. I hope that the changing landscape will reduce costs, increase productivity and improve access to these drugs.”
Patents for semaglutide have now expired in several countries, including India and China, leading to cheaper generics (although people in the US will have to wait until 2030). Andrew Hill, PhD, of the University of Liverpool – known for his analysis of how much HIV and hepatitis C drugs could cost – estimated that injectable semaglutide could be produced for just $3 a month. Brown predicted that the recently approved Vigovi pill and other future oral medications, which are easier to manufacture and distribute, will be a game changer. More than 60 experimental GLP-1 agonists and related drugs are in development for various indications, he noted, with the potential for increased competition and lower prices.
“So back to our first question. Is our interest in GLP-1 receptor agonists rational or irrational?” Brown asked. “I would say it’s logical. This class of drugs has really changed the way we treat many diseases, and we’re really at the beginning of that change.”
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