TOPLINE:
Treatment of osteoporosis with denosumab, compared with bisphosphonate therapy, may help prevent progression to type 2 diabetes (T2D) in those at high risk for it.
In patients with osteoporosis who already have established T2D, denosumab may also reduce the risk for all-cause mortality and foot ulceration, although the risk for nephropathy may increase.
METHODOLOGY:
- A retrospective analysis of data from a large global federated database including 331,375 patients without baseline T2D or cancer, prescribed either denosumab (n = 45,854) or bisphosphonates (n = 285,521), across 83 healthcare organisations.
- Propensity score matching (1:1) of confounders resulted in 45,851 patients per cohort.
- The secondary analysis assessing long-term outcomes in 40,779 patients with T2D included 5771 who were prescribed denosumab and 35,008 who were bisphosphonates.
- The systematic review assessing incident T2D yielded from four studies for meta-analysis included 185,386 participants.
TAKEAWAY:
- Treatment with denosumab significantly reduced the risk for incident T2D (hazard ratio, 0.83; P < .01), with incidence rates per 1000 person-years of 45.78 with denosumab vs 56.16 with bisphosphonates.
- The T2D risk was significantly reduced among those with overweight/obesity (hazard ratio, 0.76) but not with normal weight (0.99), and in those aged ≥ 60 years (0.80) but not in those aged < 60 years (0.76).
- In those with pre-existing T2D, denosumab was associated with lower all-cause mortality (0.79; P = .05) and a lower risk for foot ulceration (0.67; P = .01), but not retinopathy (0.79; P = .29), peripheral neuropathy (1.04; P = .93), or amputations (0.84; P = .39).
- Denosumab use was associated with an increased risk for incident nephropathy (1.33; P < .01).
- Denosumab did not reduce the risk for any cardiovascular disease (ischaemic heart disease, heart failure, or atrial fibrillation and flutter) outcomes or cerebrovascular accidents.
- In the meta-analysis, denosumab was also associated with a reduced risk for incident T2D (relative risk, 0.83; P = .52).
IN PRACTICE:
"We have conducted the largest real-world cohort study showing that patients prescribed denosumab, compared with bisphosphonates, have a 17% lower risk of developing T2D over a 5-year follow-up period…We therefore suggest a potential association of denosumab therapy in lowering incident T2D risk, above and beyond the impact of bisphosphonates, particularly in older patients with overweight or obesity…"These findings may help inform the design of future RCTs to confirm (or refute) our findings," the authors wrote.
SOURCE:
Conducted by Alex E. Henney, MBChB, of the University of Liverpool and Liverpool University Hospitals NHS Foundation trust, and colleagues, this study was published online on June 20, 2024, in Diabetes, Obesity, and Metabolism.
LIMITATIONS:
The real-world data included were not randomised or controlled for comparisons. There was potential lack of data completeness in electronic health records and potential for residual bias confounding, as by indication.
DISCLOSURES:
Alex E. Henney has no disclosures, but some co-authors do, including from industry.
