SGLT-2 inhibitors best for lowering mortality risk in T2DM : JAMA

The comparative clinical efficacy of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors for the treatment of type 2 diabetes is unknown. Dr.Zheng and his co-investigators conducted a meta-analysis to compare the efficacies of SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors on mortality and cardiovascular endpoints.The researchers found that Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide–1 (GLP-1) agonists were both associated with a lower mortality risk, compared with that seen with dipeptidyl peptidase–4 (DPP-4) inhibitors and in controls, in patients with type 2 diabetes.It implies that Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are ranked first in terms of lower mortality risk in type 2 diabetes. The meta-analysis has been published in JAMA.

International guidelines recommend SGLT2 inhibitors or incretin-based treatments in patients with type 2 diabetes who don’t achieve target glycemic control on metformin.But there is hardly any study of the relative clinical effectiveness of these drug classes, which has led to uncertainty about what treatment approach is optimal. “When no head-to-head trial exists, network meta-analysis can be used to estimate the effect,” the authors wrote.

Researchers analyzed over 250 randomized trials comparing SGLT-2 inhibitors (e.g., canagliflozin, empagliflozin), glucagon-like-peptide 1 (GLP-1) agonists (e.g., semaglutide), dipeptidyl peptidase 4 (DPP-4) inhibitors (e.g., sitagliptin, saxagliptin), and controls (placebo or no treatment) among 175,000 patients with type 2 diabetes. Among the findings:

• For low all-cause and cardiovascular mortality, the authors rank SGLT-2 inhibitors first, followed by GLP-1 agonists, and then DPP-4 inhibitors.


• SGLT-2 inhibitors were also associated with lower risk for heart failure and serious adverse events, relative to all other groups.


• GLP-1 agonists were associated with lower stroke risk than controls.


• All active treatments conferred increased hypoglycemia risk.

The authors write: "Of the 3 classes tested, SGLT-2 inhibition may be preferred over the incretin-based therapies based on their association with lower mortality and their favorable adverse event profile.Use of DPP-4 inhibitors was not associated with lower mortality than placebo or no treatment.