Practice guidelines recommend considering sodium–glucose cotransporter-2 (SGLT2) inhibitors or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for patients who have both diabetes and atherosclerotic cardiovascular disease (CVD). The choice between the drug classes is left to the physician, except that SGLT2 inhibitors are advised for patients with a history of heart failure.
Elisabetta Patorno, MD, DrPH, associate epidemiologist in the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital, Seoyoung C. Kim, MD, ScD, physician in the Division of Pharmacoepidemiology and Pharmacoeconomics and the Division of Rheumatology, Inflammation and Immunity, and Brendan M. Everett, MD, MPH, physician in the Divisions of Cardiovascular and Preventive Medicine, and colleagues recently became the first to compare the two drug classes head-to-head in this setting. In Annals of Internal Medicine, they say the findings from their observational study support current guidelines.
- This population-based observational cohort study compared the cardiovascular benefits of sodium–glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RA) in 372,080 patients with type 2 diabetes
- The risk of the primary outcome, hospitalization for myocardial infarction or stroke, was similar with the two drug classes, regardless of the presence or absence of cardiovascular disease (CVD) at baseline. However, among patients with established CVD at baseline, there was a 10% decrease in the risk of myocardial infarction or stroke in patients who started a SGLT2 inhibitor compared with those who started a GLP-1 RA
- The initiation of either SGLT2 inhibitor or GLP-1 RA therapy was associated with an approximate 30% reduction in the risk of the co-primary outcome, hospitalization for heart failure, regardless of the presence or absence of CVD at baseline
- There was no meaningful difference in the risk of all-cause mortality with SGLT2 inhibitor versus GLP-1 RA therapy, although among patients with CVD, the risk was reduced by 12% in those on SGLT2 inhibitor therapy
From Medicare data and two commercial health insurance claims databases, the researchers identified 557,109 patients with type 2 diabetes who started an SGLT2 inhibitor (canagliflozin, dapagliflozin or empagliflozin) or a GLP-1 RA (albiglutide, dulaglutide, exenatide or liraglutide) between April 1, 2013, and December 31, 2017.
They divided the study population into patients with or without baseline CVD and matched them 1:1 on a propensity score—the predicted probability of receiving an SGLT2 inhibitor versus a GLP-1 RA, conditional on 138 baseline characteristics. That left 372,080 patients: 186,040 who started an SGLT2 inhibitor and the same number who started a GLP-1 RA.
In each of the two cohorts, 52,901 patients had established CVD and 133,139 did not. The median follow-up was approximately seven months.
Hospitalization for Myocardial Infarction or Stroke
- Patients with CVD: 21.3 events per 1,000 person-years with SGLT2 inhibitors vs. 23.8 with GLP-1 RAs (HR, 0.90)
- Patients without CVD: 7.2 vs. 6.8 (HR, 1.07)
There was evidence of effect heterogeneity on both the relative scale (P=0.003) and the absolute scale (rate difference, −2.47 vs. −0.38 events per 1,000 person-years; P<0.001).
Hospitalization for Heart Failure
- Patients with CVD: 12.0 events per 1,000 person-years with SGLT2 inhibitors vs. 16.9 with GLP-1 RAs (HR, 0.71)
- Patients without CVD: 1.3 vs. 1.9 (HR, 0.69)
There was evidence of effect heterogeneity only on the absolute scale (rate difference, −4.97 vs. −0.58 events per 1,000 person-years; P<0.001).
Overall, there was no difference in the risk of all-cause mortality between patients who received SGLT2 inhibitors and those who received GLP-1 RAs. Among patients with CVD, however, the risk was reduced in those on SGLT2 inhibitor therapy (HR, 0.88).
No randomized clinical trial has ever directly compared SGLT2 inhibitors and GLP-1 RAs for their cardiovascular benefit in patients with type 2 diabetes. Industry has little incentive to conduct such trials in the future, so this study is important for clinical decision-making:
- There were no large differences between the two drug classes in the risk of myocardial infarction or stroke, although, among patients with established CVD, those who started an SGLT2 inhibitor had 10% less risk compared with those who started a GLP-1 RA
- The two drug classes were associated with 29%–31% reduced risk of hospitalization for heart failure regardless of baseline CVD status, although the absolute benefit was greater in patients with CVD