Adults with type 2 diabetes treated with semaglutide had a significantly lower risk of fracture than those treated with other weight-loss drugs, according to results from a large population-based study.
The findings run counter to concerns that GLP-1 receptor agonists may negatively affect lean body mass and possibly bone mass during weight loss.
“These findings highlight potential bone-protective effects of semaglutide, decoupling the traditional clinical concern of weight-loss induced skeletal decline,” said first author Sun H. Kim, MD, associate professor at Stanford University Medical Center in Palo Alto, California, during a presentation at ENDO 2026: The Endocrine Society Annual Meeting.
“Semaglutide represents a highly favourable option for type 2 diabetes patients, particularly those at elevated risk for bone fragility,” she said.
Patients with type 2 diabetes have an increased risk of hip fractures, Kim noted. Possible contributing factors include medications that can cause hypoglycaemia and increase fall risk, inflammation, and even hyperglycaemia, which may promote an accumulation of advanced glycation end products.
Although obesity treatment in diabetes confers wide-ranging benefits, lean mass loss has been observed with GLP-1 receptor agonist (RA) therapy and may be linked to mechanical unloading, Kim said. However, some preclinical studies suggest GLP-1 RAs may have protective effects on bone.
In a study presented by Kim and colleagues at the American Association of Clinical Endocrinology meeting in 2025, patients treated with semaglutide had fewer fractures than those who lost weight after sleeve gastrectomy (hazard ratio [HR], 0.74).
Retrospective Analysis of Fracture Risk
To further evaluate the association in patients with type 2 diabetes, the authors conducted a retrospective cohort analysis comparing semaglutide with other weight-loss drugs.
Using RxNorm and LOINC code databases, the investigators identified patients with type 2 diabetes who had no prior history of fractures or osteoporosis medication use.
Patients were stratified according to treatment with semaglutide (n = 26,324) or treatment with dulaglutide, phentermine/topiramate, or bupropion/naltrexone, with no prior semaglutide use.
After high-dimensional propensity score matching, the cohorts included 17,506 patients each. Mean age was 54.1 years in the semaglutide group and 54.5 years in the comparator group. Women comprised 55.4% and 53.9% of the groups, respectively, and mean BMI was 38.6 and 37.8, respectively.
In the subset of patients with available BMI data (4191 patient pairs), semaglutide was associated with a significantly greater reduction in BMI than the comparator drugs (-1.9 vs -1.2). The between-group difference was sustained at 1 year (-0.72; P < .001).
After a mean follow-up of 1327 days, 794 fractures occurred in the semaglutide group compared with 1045 in the control group, corresponding to fracture rates of 4.54% and 5.97%, respectively (HR, 0.85; P < .001). The results were sustained at 1 year, with a mean difference of -0.72 (P < .001) in favour of semaglutide.
“Even in the subgroups, compared either directly to dulaglutide or the other weight-loss medications, the trend persisted,” Kim said.
For people with type 2 diabetes using GLP-1 RAs, the findings are encouraging, she added.
“It would be exciting if these medications are further shown to be truly bone protective,” Kim said.
Bone Effects Remain an Open Question
More work is needed to determine whether the effect is unique to semaglutide or also applies to other GLP-1 RAs, Kim said. She noted particular interest in whether the glucose-dependent insulinotropic polypeptide component of tirzepatide may have additional bone-protective effects.
“Ideally, future directions would include a randomized trial,” she said. “Fracture incidence would be needed, and obviously it would be nice to have other imaging and bone turnover markers. Whether this benefit is specific to semaglutide compared to other GLP-1 RAs remains to be determined.”
Commenting on the study, Heide Siggelkow, MD, associate professor of endocrinology at the Clinic of Gastroenterology, Gastrointestinal Oncology and Endocrinology at the University Medical Center in Göttingen, Germany, who co-moderated the session, noted that the findings address an important question.
“Everyone is talking about GLP-1 RAs and bone and muscle,” she told Medscape Medical News. “We know that patients can lose lean mass on these drugs, but we don’t really know if it’s harmful, for instance, whether it affects function. We wonder whether it’s physiological or pathological — is it something that is gained with the weight and then lost with the weight?”
Ultimately, Siggelkow said, identifying differences among therapies could have important clinical implications.
“If one drug can be shown to be better than others, as this study suggests, that’s very important, particularly if, for instance, you have a patient who is post-menopausal and you have to choose between several options,” she said.
“If you know one can be protective, that would certainly be an advantage.”
