Denosumab Reduces Type II Diabetes Risk Save

The British Medical Journal has publish a matched cohort analysis demonstrating that adults receiving denosumab had a lower risk of incident type 2 diabetes (NIDDM) compared with those taking oral bisphosphonates for osteoporosis.

Design Population based study involving emulation of a randomized target trial using electronic health records.

Analysis of a UK primary care database between 1995-2021, looked at adults (>45 years) who used denosumab or an oral bisphosphonate for osteoporosis, They compared 4301 new users of denosumab were matched on propensity score to 21 038 users of an oral bisphosphonate users followed for a mean of 2.2 years.

They found a lower incidence of NIDDM in denosumab users (5.7 per 1000 person years) compared to oral bisphosphonate users (8.3 per 1000 PY) with a lower overall risk of type 2 diabetes (HR 0.68; 0.52 to 0.89).  This effect was also seen in those with prediabetes, where denosumab also lowered the risk (HR 0.54, 0.35 to 0.82). This was also associated with a lower rate of obesity (BMI ≥30; HR0.65; 0.40 to 1.06).

Reasons for these observations were not apparent, but there is research showing RANKL/RANK signaling pathways may be involved in energy metabolism. A 5 years, large population based study, showed higher RANKL levels were associated with a fourfold increased risk of type 2 diabetes.