The GLP-1 receptor agonist liraglutide used to treat patients with type 2 diabetes (T2D) for 26 weeks had no impact on bone resorption, even though subjects lost weight.
Liraglutide treatment also appeared to preserve hip bone mineral density vs placebo. Study findings were published online ahead of print on December 20 in the journal Bone.
"Liraglutide treatment for 26 weeks did not affect bone resorption and preserved hip BMD despite weight loss in patients with T2D, suggesting that liraglutide has some antiresorptive effect," the authors wrote.
Liraglutide is approved to reduce hyperglycemia in adults with T2D and also has been shown in animal studies to affect bone turnover by decreasing bone resorption. Writing in the background to the study, authors, led by Katrine Hygum, a doctoral student in the department of endocrinology and internal medicine at Aarhus University Hospital in Denmark, point to a reduction in bone turnover in patients with T2D that may be a result of changes in bone signaling and hyperglycemia.
The researchers note that the postprandial incretin response is reduced in T2D patients and that “incretin hormones may also affect bone turnover, but a direct effect of GLP-1 on osteoblasts is controversial.”
In the randomized double-blind clinical trial, 60 adults with T2D were assigned to treatment with liraglutide 1.8 mg daily or placebo for 26 weeks. The primary endpoint was change in p-collagen 1 cross-linked C-terminal telopeptide (p-CTX). P-CTX is a highly responsive marker of bone resorption, the magnitude of which study investigators expected to see decline.
BMD was assessed at the total hip, femoral neck, and lumbar spine at baseline, 13 weeks, and 26 weeks via DXA. Bone microarchitecture, geometry, and estimated strength also were measured at those points at the right-side radius and tibia via quantitative computed tomography.
- Among patients treated with liraglutide, CTX increased by 0.07 µg/L (95% CI, 0.03-0.1) and among patients treated with placebo by 0.03 µg/L (95% CI, 0-0.06). Changes were not different between the 2 groups.
- Subjects in the liraglutide group lost weight from baseline to week 4 (P <.001) that was sustained thereafter.
- Procollagen type 1 N-terminal propeptide (P1NP), the most sensitive biomarker of bone formation decreased among patients treated with liraglutide from baseline to week 4 (P <.01) but increased between weeks 4 and 13 (P =.03) and remained elevated thereafter.
- Weight and P1NP did not change among patients treated with placebo.
The authors conclude that the absence of effect of on bone resorption, and the preservation of BMD despite weight loss among T2D patients treated with liraglutide suggests that the GLP-1 receptor agonist may have some antiresorptive effect.
Limitations of the study include the small sample size and while all patients had T2D, not all had an indication for liraglutide and so were not necessarily representative of patients treated in real-world settings.