SGLT2 inhibitors, GLP-1 receptor agonists compared for CV, renal outcomes

Sodium-glucose cotransporter-2 (SGLT2) inhibitors were associated with fewer hospitalizations for heart failure and slower progression of kidney disease while glucagon-like peptide-1 (GLP-1) receptor agonists were associated with lower risk of stroke.


Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists reduce major adverse coronary events (MACEs) to a similar degree in patients with established cardiovascular disease (CVD), but SGLT2 inhibitors have a more marked effect on preventing hospitalization for heart failure and progression of kidney disease, a meta-analysis found.

Researchers did a systematic review and trial-level meta-analysis of trials of the two drug classes to examine rates of MACE (which they defined as a composite of myocardial infarction, stroke, and cardiovascular death), hospitalization for heart failure, and progression of kidney disease. Data from eight trials and 77,242 patients were included. Results were published Feb. 21 by Circulation.

In the study, 8,213 of 77,242 patients (10.6%) experienced a MACE (4,871 patients in the GLP-1 trials and 3,342 patients in the SGLT2 trials), and 84.7% were in patients with established CVD. Both drug classes reduced MACEs (hazard ratios [HRs], 0.88 [95% CI, 0.84 to 0.94] with GLP-1 receptor agonists and 0.89 [95% CI, 0.83 to 0.96] with SGLT2 inhibitors; P<0.001 and P=0.001, respectively). For both drug classes, this effect was only seen in patients with established CVD (HRs, 0.86 [95% CI, 0.80 to 0.93] with established CVD vs. 1.01 [95% CI, 0.87 to 1.16] without CVD; P=0.002 and P=0.81, respectively).

Both drug classes reduced the relative risk of myocardial infarction (HRs, 0.91 [95% CI, 0.84 to 0.98] with GLP-1 receptor agonists and 0.89 [95% CI, 0.80 to 0.98] with SGLT2 inhibitors; P=0.012 and P=0.018, respectively). GLP-1 receptor agonists reduced the risk of stroke (HR, 0.86; 95% CI, 0.77 to 0.97; P=0.012), while SGLT2 inhibitors had no effect (HR, 0.97; 95% CI, 0.86 to 1.10). Both drug classes significantly reduced the relative risk of cardiovascular death (HRs, 0.88 [95% CI, 0.80 to 0.96] with GLP-1 receptor agonists and 0.84 [95% CI, 0.75 to 0.94] with SGLT2 inhibitors; P=0.004 and P=0.002, respectively). SGLT2 inhibitors reduced hospitalizations from heart failure (HR, 0.69; 95% CI, 0.61 to 0.79; P<0.001) whereas GLP-1 receptor agonists did not have a significant effect (HR, 0.93; 95% CI, 0.83 to 1.04; P=0.20).

Both drugs reduced the risk of progression of kidney disease, including macroalbuminuria (HRs, 0.82 [95% CI, 0.75 to 0.89] with GLP-1 receptor agonists and 0.62 [95% CI, 0.58 to 0.67] with SGLT2 inhibitors; P<0.001 for both comparisons). Only SGLT2 inhibitors reduced the risk of worsening estimated glomerular filtration rate, end-stage kidney disease, or renal death (HR, 0.55; 95% CI, 0.48 to 0.64; P<0.001).

The distinct clinical benefit profiles of the two drug classes should be considered in the decision-making process when treating patients with diabetes, the study authors concluded. “The exact pathobiological explanations [for] how these two drug classes exert their favorable effects are still unclear,” they noted.