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Adverse Cardiovascular Events With Antidiabetic Agents

In veterans without preexisting cardiovascular disease, a retrospective cohort study from 2001 to 2019 showed that the addition of glucagon-like peptide-1 receptor agonists (GLP1RAs) was associated with fewer hospitalizations for major adverse cardiac events (MACE) and heart failure (HF), compared with dipeptidyl peptidase-4 inhibitors (DPP4i). The addition of sodium–glucose cotransporter-2 inhibitors (SGLT2i) had no association with primary MACE prevention.

Veterans aged 18 years or older receiving care from the Veterans Health Administration were included in the analysis; Medicare, Medicaid, and National Death Index data were linked to the VHA records. For veterans with diabetes adding GLP1RA, SGLT2i, or DPP4i onto metformin, sulfonylurea, or insulin treatment alone or in combination, MACE (acute myocardial infarction, stroke, or cardiovascular death) and HF hospitalizations showed these patterns: “The cohort included 28,759 GLP1RA versus 28,628 DPP4i weighted pairs and 21,200 SGLT2i versus 21,170 DPP4i weighted pairs. Median age was 67 years, and diabetes duration was 8.5 years. Glucagon-like peptide-1 receptor agonists were associated with lower MACE and HF versus DPP4i (adjusted hazard ratio [aHR], 0.82 [95% CI, 0.72 to 0.94]), yielding an adjusted risk difference (aRD) of 3.2 events (CI, 1.1 to 5.0) per 1,000 person-years. Sodium–glucose cotransporter-2 inhibitors were not associated with MACE and HF (aHR, 0.91 [CI, 0.78 to 1.08]; aRD, 1.28 [−1.12 to 3.32]) compared with DPP4i.”

Editorial: An editorialist discusses the use and misuse of observational research: “The unfortunate euphemism ‘real-world evidence’ has emerged to describe observational studies, which tends to overemphasize the value of such research. A common misconception is that a large sample size somehow corrects the inherent distortions in observational research. A large sample size does not eliminate biases related to missing data or the failure to capture all relevant outcomes. Given the limitations described earlier, the observed differences in HRs (0.82 vs. 0.91) comparing GLP1RA and SGLT2i with DPP4i are too small to derive reliable conclusions. In the current study, although [randomized controlled trials] have not been done in a pure primary prevention population, we do not have a biological reason for why effects should be different.

“In summary, large observational studies can be useful and informative, but the choice of outcomes measured and the study method must be carefully considered, and the results interpreted within the context of the study’s limitations. Caution and skepticism are appropriate when the effects are modest.”

Source: Annals of Internal Medicine