Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular disease, death and safety outcomes in type 2 diabetes – A systematic review

Abstract

There are strong overall associations of SGLT2 inhibition with protection against major cardiovascular events, heart failure, serious decline in kidney function and all-cause death. SGLT2 inhibitors were also associated with infections, volume depletion effects and amputation. Some associations appear to differ between compounds.

Cardiovascular outcomes of sodium glucose cotransporter‐2 inhibitors in patients with type 2 diabetes

“…These results were consistent among patients with and without pre‐existing CVD. We also found that use of SGLT2 inhibitors was associated with a 46% to 52% reduction in the risk of hospitalization because of heart failure, a finding that complements those reported in the EMPA‐REG, CANVAS trials and in recent observational studies . Finally, we observed a modestly lower risk of lower extremity amputation comparing use of SGLT2 inhibitors to use of sulfonylureas, but not to use of DPP‐4 inhibitors.…”

“…Similarly, the Canagliflozin Cardiovascular Assessment Study (CANVAS) trial reported a lower risk of CVD events with canagliflozin compared to placebo (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75, 0.97) . Subsequently, these results were supported by a meta‐analysis of RCTs which found a net protective effect of SGLT2 inhibitors against major CVDs (relative risk [RR], 0.85; 95% CI, 0.77, 0.93), heart failure (RR, 0.67; 95% CI, 0.55, 0.80) and all‐cause death (RR, 0.79; 95% CI, 0.70, 0.88) …”

Cardiovascular efficacy and safety of sodium‐glucose co‐transporter‐2 inhibitors and glucagon‐like peptide‐1 receptor agonists: a systematic review and network meta‐analysis

“…Core outcome sets were defined in the protocol of the RCTs, which aimed to reduce selective reporting biases, but in many cases the unavailability of data was in safety (adverse events) outcomes. Despite sparse data for some outcomes, all models appeared to converge from visual analysis of history and trace plots, and the estimates from pairwise analyses and network meta-analyses in the present study were similar to those from meta-analyses conducted previously [10][11][12][13]41]. Furthermore, it was not possible to assess individual treatments in the network but only combined in treatment groups; however, by comparing the class effects of treatments, rather than individual treatment effects, statistical power was increased.…”

Observational research on sodium glucose co‐transporter‐2 inhibitors: A real breakthrough?

“…A novel informative MA should assess renal outcomes such as progression to albuminuria or serious decline in renal function, unquantified outcomes (infections), and debated issues such as BKAs or fractures 72. From a methodological viewpoint, individual patient‐data MAs and head‐to‐head RWD from observational studies could represent a viable research option, such as the OBSERVE‐4D meta‐analytic approach 24…”