Spotlight on efficacy of SGLT-2 inhibitors and GLP-1 receptor agonists

Several recent studies tried to evaluate the efficacy of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists.

A Taiwanese study, published by Diabetes, Obesity and Metabolism on May 1, matched 26,032 patients with type 2 diabetes who started either a GLP-1 receptor agonist or an SGLT-2 inhibitor between 2012 and 2018. The median follow-up was approximately 0.6 years in the primary on-treatment analysis. They found similar risks of several outcomes: myocardial infarction (hazard ratio [HR], 0.99; 95% CI, 0.65 to 1.52), total stroke (HR, 0.90; 95% CI, 0.69 to 1.17), ischemic stroke (HR, 0.86; 95% CI, 0.65 to 1.14), and hemorrhagic stroke (HR, 0.88; 95% CI, 0.63 to 1.25). Among patients with kidney disease, GLP-1 receptor agonists were associated with an increased risk of total stroke (HR, 1.76; 95% CI, 1.06 to 2.94) and ischemic stroke (HR, 1.88; 95% CI, 1.09 to 3.23), but not in patients without chronic kidney disease (HRs, 0.86 [95% CI, 0.62 to 1.21] and 0.80 [95% CI, 0.55 to 1.115], respectively). However, in patients with cardiovascular disease, GLP-1 receptor agonists were associated with a lower risk of hemorrhagic stroke (HR, 0.64; 95% CI, 0.43 to 0.97) but not in patients without cardiovascular disease. The study authors concluded that they did not observe substantial differences in the risks of myocardial infarction and stroke between the two drug classes but that there appeared to be some differences based on the presence of kidney or cardiovascular disease. There are mechanisms that could possibly explain these differences in effects, but limitations of the study included potential for confounding and short follow-up (about half a year), they noted.

A meta-analysis, also published by Diabetes, Obesity and Metabolism on May 1, focused on 27 trials that randomized patients with type 2 diabetes to a GLP-1 receptor agonist or SGLT-2 inhibitor and reported cardiovascular or renal events or all-cause mortality. The meta-analysis found significant variation among the trials in the probability that the drugs were superior to placebo for these outcomes. For GLP-1 receptor agonists, the probability ranged from 0% to 69% for prevention of a cardiorenal event and 0% to 8% for mortality. For SGLT-2 inhibitors, the respective ranges were 0% to 96% and 0% to 93%. The study authors noted that the probabilities were higher on average for SGLT-2 inhibitors, particularly in trials with renal or heart failure outcomes. “These results demonstrate within- and between-class differences, highlight the drawbacks of a binary interpretation of the results, particularly in the context of the current designs of noninferiority trials, and have implications for decision makers and future clinical recommendations,” they wrote.

Finally, a study published by BMJ Open Diabetes Research & Care on March 29 looked at 34,376 Italian patients with diabetes and heart failure. Two cohorts of patients were included, among whom slightly less than 4% were on an SGLT-2 inhibitor, less than 4% were on an GLP-1 receptor agonist, about half were on insulin, and more than a third were on other diabetes medications. The analysis found that both SGLT-2 inhibitors and GLP-1 receptor agonists were associated with lower risk of a major cardiovascular event or death compared with insulin (HRs, 0.29 and 0.482, respectively). They were also associated with lower risk of first hospitalization for heart failure (HRs, 0.57 and 0.67, respectively). The study authors said that their results provide the “first consistent evidence that long-term treatment [with either drug class] compared with insulin is associated with a significant reduction of risk” for the studied outcomes. They noted, however, that patients in the insulin cohort were undertreated with other recommended cardiovascular medications and metformin, which could have affected the findings.