SGLT2 inhibitors associated with reduced risk of CV and renal events

Meta-analysis of 6 outcomes trials of 4 sodium-glucose cotransporter 2 (SGLT2) inhibitors in type 2 diabetes (T2DM) patients shows SGLT2 inhibitors are associated with reduced risk of major adverse cardiovascular (CV) events and CV death, the latter showing significant heterogeneity. The largest magnitude of benefit was for reduction in risk of renal disease progression and hospitalisation for heart failure (HHF), with estimates of HHF risk outcome the most consistent observation across the trials in this class

The aim of this meta-analysis was to combine the data from 6 placebo-controlled cardiovascular and renal outcomes trials of SGLT2 inhibitors in T2DM patients from 2015 to 2020 to assess the heterogeneity of all SGLT2 inhibitors on cardiovascular and renal outcomes and whether trends are observed across the drug class.

The outcomes trials included in the meta-analysis are:

• CANVAS programme (2 trials), canagliflozin cardiovascular assessment study;
• CREDENCE, evaluation of the effects of canagliflozin on renal and cardiovascular outcomes in participants with diabetic nephropathy;
• DECLARE-TIMI 58, multicenter trial to evaluate the effect of dapagliflozin on the incidence of cardiovascular events;
• EMPA-REG OUTCOME, empagliflozin cardiovascular outcome event trial in type 2 diabetes mellitus patients;
• VERTIS CV, cardiovascular outcomes following ertugliflozin treatment in type 2 diabetes mellitus participants with vascular disease.

Overall, SGLT2 inhibitors were associated with reduced risks of

• major adverse CV events (HR, 0.90; 95%CI, 0.85-0.95)
• HHF (HR, 0.68; 95%CI, 0.61-0.76)
• renal events (HR, 0.62; 95%CI, 0.56-0.70)

The presence or absence of atherosclerotic CV disease did not modify the association with outcomes for major adverse CV events (P = 0.63 for interaction), nor for HHF/CV death (P = 0.62 for interaction), HHF (P = 0.26 for interaction), or renal outcomes (P = 0.73 for interaction).

These data support current international guideline recommendations to prioritise the use of SGLT2 inhibitors with demonstrated outcomes, independent of glucose control considerations, in patients with T2DM with or at high risk for renal complications or heart failure; for T2DM patients with or at high risk for CV complications SGLT2 inhibitors are recommended after glucagon-like peptide 1 receptor agonist (GLP-1 RA).