Adults with type 2 diabetes and established cardiovascular disease treated with an SGLT2 inhibitor have lower risks for all-cause mortality, hospitalization for heart failure and major adverse CV events compared with those treated with other antihyperglycemic agents, data from a population-based cohort study show.
“The role of pharmacoepidemiologic studies goes beyond an ability to validate whether clinical trial results are reproducible in a generalizable patient population,” the researchers wrote. “Observational studies are also critical in filling a knowledge gap to inform about the real-world effectiveness of new therapies and potential serious adverse events not readily detected in clinical trials.”
In the EASEL study, Jacob A. Udell, MD, MPH, of the cardiovascular division, department of medicine at Peter Munk Cardiac Centre in Toronto, and colleagues evaluated data from the U.S. Department of Defense Military Health System on 25,258 adults with type 2 diabetes who initiated SGLT2 inhibitors (n = 12,269; mean age, 65.8 years; 56.7% men; 36.7% white) or non-SGLT2 inhibitor antihyperglycemic agents (n = 12,269; mean age, 65.9 years; 55.1% men; 33.6% white) between April 1, 2013, and Dec. 31, 2016, to determine the effect of drug choice on CV risk. The newly initiated SGLT2 inhibitors included canagliflozin (Invokana, Janssen), empagliflozin (Jardiance, Boehringer Ingelheim) and dapagliflozin (Farxiga, AstraZeneca). Follow-up was a median 1.6 years.
Participants had similar diabetes duration (5.7 years for non-SGLT2 initiators vs. 5.6 years for initiators) and CVD duration (4.4 years for both).
Outcomes included a composite endpoint of all-cause mortality and hospitalization for heart failure and major CV events, including all-cause mortality, nonfatal myocardial infarction and nonfatal stroke.
Participants who initiated SGLT2 inhibitors had lower incidence rates of all-cause mortality (1.29 vs. 2.26 events per 100 person-years; HR = 0.57; 95% CI, 0.49-0.66) and hospitalization for heart failure (0.51 vs. 0.9 events per 100 person-years; HR = 0.57; 95% CI, 0.45-0.73) compared with non-SGLT2 initiators. Further, SGLT2 initiators had a lower incidence rate for major adverse CV events compared with non-SGLT2 initiators (2.31 vs. 3.45 per 100 person-years; HR = 0.67; 95% CI, 0.6-0.75). No differences were observed for the rates of nonfatal MI and nonfatal stroke between the two groups.
SGLT2 initiators had twice the rate of below-the-knee amputations compared with non-SGLT2 initiators (0.17 vs. 0.09 per 100 person-years; HR = 1.99; 95% CI, 1.12-3.51).
“While these observations require replication in other settings, our findings underscore the potential CV benefit and a rare but serious risk that physicians and patients should monitor for when initiating this class of medication,” the researchers wrote. – by Amber Cox
Disclosures: Udell reports he receives consulting fees or speaking honoraria from Amgen, Boehringer Ingelheim, Janssen, Merck, Novartis and Sanofi Pasteur and research grant support from AstraZeneca and Novartis. Please see the study for all other authors’ relevant financial disclosures.