(B12) Effect of Bisphosphonates versus Denosumab on Risks of Cardiovascular Events in Patients with Type 2 Diabetes

Publication Number: 624

Background: Compared to non-diabetes, individuals with type 2 diabetes mellitus (T2DM) are more likely to comorbid with osteoporosis and receive corresponding treatment, such as bisphosphonates (BP) and denosumab (DS). Current evidence shown controversial findings of these medications in association with cardiovascular events, which are the main complications that increase mortality in diabetic patients. However, there was lack of comparative studies conducted in patients with T2DM.

Objectives: To compare BP with DS in risks of multiple cardiovascular events in T2DM patients.

Methods: This was a cohort study applying Taiwan’s National Health Insurance Database. We identified T2DM patients who had been diagnosed with osteoporosis and received any BP or DS during 2013 to 2018. Further, we excluded those treated with BP and DS at the same date. For DS users, the first prescription date of DS was defined as the index date. Each DS user was matched to a BP user on sex, birth year and prior treatment duration of BP. Outcomes of interest included acute coronary syndrome (ACS), myocardial infarction (MI), ischemic stroke (IS) and peripheral arterial disease (PAD). Individuals who had experienced events before index date were excluded and the rest were followed until event occurrence, death, disenrollment or end of study period (Dec 31 2020). To control confounders, we calculated a propensity score (PS) of being treated by BP for each individual, considering their demographics, comorbidities, medication histories and healthcare utilization pattern. Inverse probability treatment weighting (IPTW) of PS was applied in the Cox hazard model to calculate the hazard ratios of outcomes for BPs versus DS. To account for competing risk by death, subdistribution model was applied. We also conducted per-protocol analysis as sensitivity analysis and performed subgroup analysis by sex, CKD status and age.

Results: After matching and exclusion of those with prior events, a total of 13210 patients (6605 pairs) were included. Mean(SD) age was 74(9) years and 87% were female. Compared to BP users, DS users had higher comorbidity index, proportion of CKD and history of recent hospitalization. After a median follow-up of 2 years, a total of 414 ACS, 233 MI, 638 IS and 391 PAD events were observed. After PS IPTW, BP use was found with lower risks of ACS (HR 0.76, 95%CI 0.63 to 0.92) and MI (HR 0.72, 95%CI 0.55 to 0.93). However, risks of IS and PAD showed no significant difference. Per-protocol analysis showed similar results with slightly wider confidence intervals. From subgroup analysis, lower HRs of ACS and MI were found in female and CKD subgroups.

Conclusions: For T2DM patients with osteoporosis, use of BP lowered risks of ACS and MI when compared to DS.