Study finds long-term reductions in cardiovascular risk factors with SGLT-2 inhibitors
While the meta-analysis also found durable reductions in macrovascular complications and mortality with sodium-glucose cotransporter-2 (SGLT-2) inhibitors versus placebo, there were insufficient data comparing the drug class to other antihyperglycemic medications.
A recent meta-analysis found long-term reductions in cardiovascular risk factors with sodium-glucose cotransporter-2 (SGLT-2) inhibitors versus other antihyperglycemic medications or placebo.
Researchers looked at randomized controlled trials of at least 52 weeks' duration that were published through July 2019, enrolled patients with type 2 diabetes, and compared SGLT-2 inhibitors with placebo or other antihyperglycemic medications. Included studies reported at least one outcome of interest, such as cardiovascular risk factors, microvascular and macrovascular complications, mortality, and adverse events. Results were published Nov. 30 by the Journal of General Internal Medicine.
The analysis included 50 articles describing 39 trials involving 112,128 patients with type 2 diabetes. Twenty-eight trials (median follow-up duration, 76 weeks) compared SGLT-2 inhibitors with placebo, 12 trials (median follow-up duration, 52 weeks) compared SGLT-2 inhibitors with other antihyperglycemic medications, and one trial compared an SGLT-2 inhibitor with both placebo and another antihyperglycemic medication. The other antihyperglycemic medications were metformin in one trial, a dipeptidyl peptidase-4 inhibitor in six trials, and a sulfonylurea in five trials.
Compared to placebo, SGLT-2 inhibitors reduced cardiovascular risk factors such as HbA1c level (mean difference, −0.55%; 95% CI, −0.62% to −0.49%), macrovascular outcomes such as hospitalization for heart failure (relative risk [RR], 0.70; 95% CI, 0.62 to 0.78), and mortality (RR, 0.87; 95% CI, 0.80 to 0.94). Compared with other antihyperglycemic medications, SGLT-2 inhibitors reduced cardiovascular risk factors (mean difference for HbA1c level, −0.11%; 95% CI, −0.21% to −0.01%), but there were insufficient data available to compare the drug class to other antihyperglycemic medications for microvascular outcomes, macrovascular outcomes, or mortality. There was about a fourfold increased risk of genital yeast infections for men and women in comparisons of SGLT-2 inhibitors versus placebo and other antihyperglycemic agents.
Among other limitations, the meta-analysis excluded observational studies and was restricted to a limited number of prespecified outcomes, the authors noted. They added that they combined all antihyperglycemic medications into one comparator group, although they compared different medication classes in subgroup analyses when possible.
“While significant attention has been paid to the large [cardiovascular] outcome trials, our study reveals the sparsity of evidence on the effectiveness of SGLT2 [inhibitors] compared to other anti-hyperglycemic medications in longer-term randomized controlled trials. … These results help inform shared decision-making discussions regarding the benefits and risks in prescribing SGLT2 [inhibitors] for patients with [type 2 diabetes],” the authors concluded.