Conference Coverage

CVD-REAL 2: Lower mortality, CV risks with SGLT-2i vs. DPP-4i treatment in T2DM



Initiation of treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor is associated with significantly lower risks of death, cardiovascular events, and stroke, compared with initiation of dipeptidyl peptidase–4 (DPP-4) inhibitor treatment in patients with type 2 diabetes mellitus, according to findings from the CVD-REAL 2 study.

CVD-REAL 2 is a real-world, observational cohort study involving the analysis of health records for two matched cohorts of patients with T2DM from 12 countries across the globe, including 181,620 SGLT-2 inhibitor recipients and 181,620 DPP-4 inhibitor recipients who were newly initiated on their respective treatments between December 2012 and November 2017. The respective rates of all-cause death were 0.83 and 1.33 per 100 patient-years (4,768 events; hazard ratio, 0.51), Shun Kohsaka, MD, of Keio University School of Medicine, Tokyo, and his colleagues reported in a late-breaking poster at the annual scientific sessions of the American Diabetes Association.

“HRs for all-cause death consistently favored SGLT-2 inhibitor vs. DPP-4 inhibitor in each country,” the investigators noted. “Directionally, the same results were observed in other cardiovascular outcomes, including [hospitalization for heart failure (HHF)], and the composite of all-cause death or HHF but modestly for [myocardial infarction] and stroke.”

The rates of hospitalization for heart failure per 100 patient-years were 0.80 and 1.08 in the SGLT-2 inhibitor and DPP-4 inhibitor groups (3,875 events; HR, 0.68), and for HHF plus all-cause death, they were 1.55 and 2.22 per 100 patient-years (7,807 events; HR, 0.67), respectively. The rates of myocardial infarction in the groups, respectively, were 0.53 and 0.58 per 100 patient-years (2,298 events; HR, 0.90), and for stroke, they were 0.82 and 0.99 per 100 patient-years (3,747 events; HR, 0.84), the investigators reported.

Study subjects in both cohorts had a mean age of 58 years, and 30% and 29% in the SGLT-2 inhibitor and DPP-4 inhibitor groups, respectively, had established cardiovascular disease. Only those newly initiated on either an SGLT-2 inhibitor or DPP-4 inhibitor were selected from each data source; fixed-dose combinations were allowed as long as there was no use of either drug during the year prior to enrollment.

In the SGLT-2 inhibitor cohort, most exposures (60.1%) were to dapagliflozin, followed by canagliflozin (23.8%) and empagliflozin (12.1%). The remaining exposures were to ipragliflozin, tofogliflozin, or luseogliflozin (0.3-2.8%). In the DPP-4 inhibitor group, most exposures (49.7%) were to sitagliptin, 18.9% were to linagliptin, 10.4% were to saxagliptin, and the remaining exposures were to alogliptin, gemigliptin, teneligliptin, anagliptin, evogliptin, and trelagliptin (0.1%-4.7%).

Those in the SGLT-2 inhibitor group were followed for a mean of 439 days, and those in the DPP-4 inhibitor group were followed for a mean of 446 days.

“The results were consistent across the subgroups of patients with and without established [cardiovascular disease], favoring SGLT-2 inhibitor vs. DPP-4 inhibitor for all outcomes,” they noted.

Both DPP-4 inhibitors and SGLT2 inhibitors are widely used in T2DM, and although clinical trials demonstrated lower risk of cardiovascular events with SGLT-2 inhibitors and a neutral effect on cardiovascular events with DPP-4 inhibitors, large comparative studies are lacking, the investigators explained.

Though limited by the possibility of residual, unmeasured confounding, as well as by a lack of mortality data in Japan and Singapore apart from the inpatient setting, the findings of this “large, contemporary analysis of real-world administrative data” are complementary to those from previous observational studies and clinical trials, they concluded, noting that “SGLT-2 inhibitor experience in real-world practice is still relatively short and longer-term follow-up is required to examine whether effects are sustained over time.”

The CVD-REAL studies are sponsored by AstraZeneca. Dr. Kohsaka reported receiving research support from Bayer Yakuhin and Daiichi Sankyo and serving on the speaker’s bureau for Bayer Yakuhin and Bristol-Myers Squibb.

SOURCE: Kohsaka S et al. ADA 2018, Abstract 124-LB.

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