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Effect of denosumab on fasting glucose in women with diabetes or prediabetes from the FREEDOM trial
Author(s) -
Napoli Nicola,
Pannacciulli Nicola,
Vittinghoff Eric,
Crittenden Daria,
Yun Jang,
Wang Andrea,
Wagman Rachel,
Schwartz Ann V.
Publication year - 2018
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.2991
Subject(s) - prediabetes , placebo , denosumab , medicine , diabetes mellitus , randomized controlled trial , endocrinology , urology , type 2 diabetes , osteoporosis , alternative medicine , pathology
Background RANKL is a key regulator of bone resorption that may also modulate glucose metabolism. Denosumab (DMAb) is a fully human monoclonal antibody that binds RANKL and was associated with fracture risk reduction in the FREEDOM trial. We hypothesized that DMAb treatment decreased fasting serum glucose (FSG) relative to placebo in women with diabetes or prediabetes enrolled in FREEDOM trial. Methods Post hoc analysis of FREEDOM, in which 7808 postmenopausal osteoporotic women were randomized to receive DMAb or placebo every 6 months for 36 months. All diabetes group included subjects with a self‐report of diabetes, use of antidiabetic medication (ADM), or an FSG ≥ 126 mg/dL at baseline. The diabetes group without prior ADM use included subjects with a self‐reported history of diabetes or FSG level ≥ 126 mg/dL at baseline. Prediabetes was defined as an FSG of 100 to 125 mg/dL on no ADM. Average postbaseline FSG across visits was estimated and compared between DMAb and placebo . Main outcome measures are the difference in average postbaseline FSG across follow‐up visits between DMAb and placebo. Results Estimated average postbaseline FSG across visits was not different between DMAb and placebo in either all diabetes group ( P = .20) or those with prediabetes ( P = .42); in diabetic women not on ADM, estimated average postbaseline FSG across visits was lower with DMAb than placebo (−6.8 mg/dL; 95% CI, −12.6 to −1.0; P = .02). Conclusions DMAb did not affect FSG in postmenopausal osteoporotic women with prediabetes or diabetes. There was evidence of modest FSG lowering with DMAb in those with diabetes who were not on ADM. It remains to be determined whether blockade of RANKL has a clinically important effect on glucose metabolism.