Does Liraglutide Affect Bone Turnover in Type 2 Diabetes?

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In patients with type 2 diabetes, treatment with liraglutide does not affect bone resorption and preserves hip bone mineral density, even with weight loss.

In patients with type 2 diabetes (T2D), treatment with liraglutide does not affect bone resorption and preserves hip bone mineral density (BMD), even with weight loss, according to study results published in Bone.

Animal studies have shown a possibly beneficial relationship between treatment with liraglutide, a glucagon-like peptide-1 receptor agonist, and bone turnover in obese mice. To examine this relationship in patients with T2D, researchers conducted a prospective study of 60 individuals who were randomly assigned to treatment with liraglutide 1.8 mg or placebo daily for 26 weeks. The study’s primary end point was change in plasma level of C-terminal telopeptide of type 1 collagen (CTX). The researchers chose CTX as the primary end point because it is the most responsive marker of bone resorption.

Secondary outcomes included changes in the bone formation markers bone alkaline phosphatase, osteocalcin, and procollagen type 1 N-terminal propeptide (P1NP) and changes in BMD.

At 26 weeks, the researchers observed increased plasma CTX in patients treated with liraglutide (0.07 μg/L; 95% CI, 0.03-0.10; P <.001) and in patients treated with placebo (0.03 μg/L; 95% CI, 0.00-0.06; P =.04) compared with baseline. The difference in changes between the 2 groups was not statistically significant (P =.16).

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From baseline to week 4, patients with liraglutide had a weight decrease (-3.8 kg; 95% CI, 2.5-5.2; P <.001) that remained stable afterwards. Patients treated with liraglutide also had lower levels of plasma P1NP from baseline to week 4 (P <.01), which increased between weeks 4 and 26 (P =.001). Patients treated with placebo did not have significant changes in weight or P1NP. Neither group showed significant changes for other markers of bone formation.

The results also indicated that from baseline to study end, patients treated with placebo had a decrease in BMD at the total hip compared with no change in patients treated with liraglutide (P =.01 for difference between groups). There was no interaction between treatment and time with regard to BMD at the femoral neck or lumbar spine.

The study had several limitations, including its short study period. The researchers also noted that they were unable to assess the effects of changing plasma glucose in different phases of the study, as they only measured hemoglobin A1c at baseline and at the end of the study period and did not record plasma glucose levels.

“Liraglutide treatment for 26 weeks prevented changes in bone resorption and preserved hip BMD despite weight loss in patients with T2D, thus suggesting that liraglutide has some antiresorptive effect,” the researchers wrote.

Disclosure: This clinical trial was supported by Novo Nordisk Scandinavia. Please see the original reference for a full list of authors’ disclosures.

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Hygum K, Harsløf T, Jørgensen NR, Rungby J, Pedersen SB, Langdahl BL. Bone resorption is unchanged by liraglutide in type 2 diabetes patients: a randomised controlled trial. Bone. 2020;132:115197.