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Denosumab modestly improves fasting glucose in some women with diabetes

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February 16, 2018

In a small subset of postmenopausal women with osteoporosis and diabetes who were not prescribed antidiabetes medications, the osteoporosis drug denosumab was shown to modestly improve fasting serum glucose over 3 years compared with placebo, according to a post hoc analysis of the FREEDOM trial.

Denosumab (Prolia, Amgen) is a monoclonal antibody that blocks the interaction of receptor activator of nuclear factor kappa- ligand, or RANKL, with its receptor, RANK, reducing osteoclast number and activity, Nicola Napoli, MD, of the division of endocrinology and diabetes at the University Campus Bio-Medico di Roma, Italy, and colleagues wrote in the study background. Recent research suggests that RANKL may also contribute to glucose regulation and may have a role in beta-cell replication.

“Nonclinical studies showed that RANKL signaling blockade enhances glucose metabolism in mouse models of impaired glucose homeostasis, including insulin resistance and overt diabetes,” Napoli and colleagues wrote. “Therefore, it could be speculated that the effect of RANKL blockade on glucose regulation is only evident when an impairment of glucose tolerance has already begun.”

Napoli and colleagues analyzed data from 1,934 postmenopausal women aged 60 to 90 years with osteoporosis and prediabetes or diabetes, randomly assigned to 60 mg denosumab once every 6 months for 36 months or placebo, in addition to daily oral calcium and vitamin D. Researchers measured fasting serum glucose at baseline, 1 month and every 6 months until study completion. Patients were stratified into three groups: patients with diabetes prescribed antidiabetes medications (n = 372), patients with diabetes not prescribed antidiabetes medications (n = 294) and patients with prediabetes (n = 1,268). Researchers used mixed models for repeated measures to estimate the effects of treatment on post-baseline fasting serum glucose levels.

In analyzing all women with diabetes, researchers did not observe between-group differences for post-baseline fasting serum glucose measurements for women assigned denosumab vs. placebo. However, in assessing only women with diabetes not prescribed antidiabetes medications, those assigned denosumab had a lower estimated average post-baseline fasting serum glucose compared with those assigned to placebo (114.9 mg/dL vs. 121.7 mg/dL; least squares mean, –6.8; P = .02). There were no differences observed among women with prediabetes, according to researchers.

“It remains to be determined whether blockade of RANKL has a clinically important effect on glucose metabolism,” the researchers wrote. – by Regina Schaffer

Disclosures: Napoli reports receiving consultant fees from Amgen. Please see the study for the other authors’ relevant financial disclosures.

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