Initiation of SGLT2i vs. DPP-4i associated with lower risk of CV events in T2DM
Risk of cardiovascular events and death associated with initiation of SGLT2 inhibitors compared with DPP-4 inhibitors: an analysis from the CVD-REAL 2 multinational cohort study
Introduction and methods
SGLT2i and DPP-4i are glucose lowering drugs used in the treatment of T2DM. CV outcome trials showed that SGLT2i reduced the risk of major adverse CV events in patients with T2DM and atherosclerotic CVD (ASCVD) or CKD [1,2]. In addition, SGLT2i also reduced the risk of hospitalization for HF in patients with T2DM with and without ASCVD [1, 3-5]. In contrast, DPP-4i have shown no effect on ischemic events or CV death and the DPP-4i sitagliptin has shown no effect on hospitalization for HF [5-9]. To date, there are no clinical trials that directly compare SGLT2i with DPP-4i in terms of CV effects. This comparative cohort analysis from the CVD-REAL 2 study used data from de-identified health records from 13 countries (Australia, Canada, Denmark, Germany, Israel, Japan, Norway, Singapore, South Korea, Spain, Sweden, Taiwan, and the USA). These data were used to assess the risk of CV events and death in adults with T2DM newly initiated on SGLT2i compared with those newly initiated on DPP-4i.
A non-parsimonious propensity score for initiating a SGLT2i was developed within each country. Based on the propensity scores, patients initiating a SGLT2i were matched in a 1:1 ratio with patients initiating a DPP-4i. 193124 new users of a SGLT2i and 193124 new-users of a DPP-4i were included in the analysis. Mean age was 58 (SD 12.2) years, 44.1% were women and 30.1% had established CVD.
Studied outcomes were hospitalization for HF, all-cause death, the composite of hospitalization for HF or all-cause death, non-fatal myocardial infarction (MI), and non-fatal stroke. An intention-to-treat (ITT) approach was used in the primary analysis in which patients were followed-up from the start of index treatment until either occurrence of the first outcome event, or the censoring date. Data for deaths were available for all 13 countries. Data for the other outcomes were available for 12 countries (No data from Australia was available).
- Initiation of a SGLT2i versus a DPP-4i was associated with substantially and significantly lower risks of hospitalization for HF (ITT unadjusted approach, pooled HR 0.69, 95%CI 0.61-0.77, P<0.0001), all-cause death (ITT unadjusted approach, pooled HR 0.59, 95%CI 0.52-0.67, P<0.0001), and the composite outcome of hospitalization for HF or all-cause death (ITT unadjusted approach, pooled HR 0.64, 95%CI 0.57-0.72, P<0.0001). Results showed that HRs consistently favored SGLT2i over DPP-4i in each studied country. ITT multivariate-adjusted and on-treatment analyses showed similar results.
- Initiation of a SGLT2i versus a DPP-4i was associated with modestly but significantly lower risk of MI (ITT unadjusted approach, pooled HR 0.88, 95%CI 0.80-0.98, P=0.020) and stroke (ITT unadjusted approach, pooled HR 0.85, 95%CI 0.77-0.93, P=0.0004). HR’s for MI and stroke favored SGLT2i over DPP4i most countries (11 out of 12 countries). ITT multivariate-adjusted and on-treatment analyses showed similar results.
- Subgroup analyses were performed in patients with and without CVD at baseline. Initiation of a SGLT2i versus a DPP-4i was associated with significantly lower risks of hospitalization for HF, all-cause death, and the composite of both outcomes, with no significant interactions across subgroups. HRs favored SGLT2i over DPP-4i for MI and stroke in both subgroups with no significant interactions across subgroups. However, HRs were not significant for the subgroup with established CVD at baseline for the outcomes MI and stroke.
This international, comparative cohort study showed that initiation of SGLT2i versus DPP-4i in adults with T2DM was associated with substantially lower risks of hospitalization for HF and all-cause death and with modestly, but significantly lower risks of MI and stroke in clinical practice. These findings support previous evidence for the CV benefits associated with use of SGLT2i in T2DM.