In a new study published in the JAMA Network Open medical journal, Novo Nordisk A/S’s Saxenda (liraglutide), an earlier-generation weight loss drug, reveals significant declines in bone density among patients in the hips, spine, and forearm.

The study, led by Signe Sørenson Torekov of Copenhagen University, suggests that while these medications effectively reduce weight, they may compromise bone health due to caloric restriction and hormonal changes.

195 participants were randomized, with 48 participants in the exercise group, 49 in the liraglutide group, 49 in the combination group, and 49 in the placebo group.

The total estimated mean change in weight loss during the study was 7.03 kg in the placebo group, 11.19 kg in the exercise group, 13.74 kg in the liraglutide group, and 16.88 kg in the combination group. 

The observation that bone mass density (BMD) decreased with liraglutide alone but not in combination with exercise supports using exercise with obesity medications in populations with reduced bone mass (e.g., after menopause).

The low-calorie diet increased P-CTX, the marker of bone resorption (destruction of bone tissues), by 27% and P-P1NP, the marker of bone formation, by 7%.

From week 26, P-CTX decreased again in all treatment groups, reflecting more stable body weight development. No changes in P-P1NP were observed in any active treatment group compared with placebo, suggesting that bone formation was not suppressed despite the concomitant weight reductions.

Bloomberg notes that the finding raises alarms about similar effects in newer, more potent treatments like Wegovy and Eli Lilly And Co’s Zepbound, which induce greater weight loss.

The study notes that despite a substantial weight loss of 16.9 kg for the combination group vs 7.0 kg for the placebo group, the combination treatment preserved site-specific BMD compared with placebo.

Thus, in the combination group, the preserved bone mass was observed despite a weight reduction of a magnitude that is clinically relevant in the context of novel incretin-based obesity therapies, such as semaglutide and tirzepatide, which resulted in weight losses of around 15% to 19% in a systematic review.

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