In primary prevention, SGLT-2i reduce both the risk of hospitalization for HF and progression of DKD; in secondary prevention, SGLT-2i are effective on the three endpoints, DPP-4i are neutral, while GLP1-RA show mixed results.
The four trials with dipeptidyl-peptidase inhibitors (DPP-4i) (SAVOR-TIMI 53 with saxagliptin, EXAMINE with alogliptin, TECOS with sitagliptin and CARMELINA with linagliptin) failed to show any significant effect on HF risk in patients with T2D, with the notable exception of saxagliptin which was associated with a 27% increased risk.
The risk of MI for DPP-4I users was similar to that for α-GI users, while the risk of HF for DPP-4I users was slightly higher than for α-GI users (MI: aHR, 0.98 [95%CI, 0.82-1.17], HF: aHR, 1.12[95%CI, 1.04-1.21]).
Thus, this comprehensive review summarizes the CV outcomes (excluding heart failure) reported in meta-analyses of randomized controlled trials (RCTs) of SUs vs placebo or other glucose-lowering agents, DPP-4is vs placebo or other glucose-lowering agents and SUs vs DPP-4is in phase-II/III studies.
Thus, we aimed to evaluate whether the heart failure protective effect of SGLT-2i differs depending on the underlying CVD and the prescription period compared with dipeptidyl peptidase-4 inhibitors (DPP-4i).
Most recent studies with DPP-4is do not confirm the increased risk of hospitalisation for heart failure reported with saxagliptin in SAVOR-TIMI 53, but further post-marketing surveillance is still recommended.
During a 30 month period, the hazard ratio for heart failure admission to hospital associated with canagliflozin was 0.70 (95% confidence interval 0.54 to 0.92) versus a DPP-4i (n=17 667 pairs), 0.61 (0.47 to 0.78) versus a GLP-1RA (20 539), and 0.51 (0.38 to 0.67) versus a sulfonylurea (17 354 ).
We examined IV strength and estimated risk differences (RDs) for HF using Kaplan-Meier curves, which were compared with propensity score (PS)-weighted RD for DPP-4i versus TZD.
The hazard ratios (HRs) of hospitalization for HF for DPP-4i-treated patients were 0.78 (95% confidence interval [CI], 0.67-0.86) in all of the patients, 0.77 (95% CI, 0.68-0.79) in patients with baseline cardiovascular disease, and 0.71 (95% CI, 0.56-0.90) in patients without baseline cardiovascular disease compared with HRs for sulfonylurea-treated patients.