Effects of newer anti-hyperglycemic agents on cardiovascular outcomes in older adults: Systematic review and meta-analysis

Aim

To demonstrate cardiovascular safety of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and sodium/glucose cotransporter 2 inhibitors (SGLT-2i) across age-groups.

Methods

PubMed, Embase and Cochrane were searched for cardiovascular outcome trials (CVOTs) testing newer agents until August 31, 2022 (PROSPERO ID CRD42021260167). Studies with ≥1000 T2D participants enrolled for ≥12 months were included. Random effect models were used to report relative-risk (RR) for three-point major adverse cardiovascular events (3P-MACE) and its components by age subgroups (65 years; 75 years).

Results

For SGLT-2is, five CVOTs (46,969 patients, 45–50 % ≥65 years) were included. SGLT-2is reduced risk of MACE (RR; 0.91 [CI, 0.85–0.98]); cardiovascular death (CV-death) (RR; 0.84 [CI, 0.73–0.96]); and all-cause mortality (ACM) (RR; 0.86 [CI, 0.79–0.93]) with no difference in subgroups <65 or ≥65 years.

For GLP-1RAs, nine CVOTs (n = 64,236, 34–75 % ≥65 years) were included. GLP-1RAs reduced risk of MACE (RR; 0.89 [CI, 0.83–0.95]), stroke (RR; 0.86 [CI, 0.76–0.97]) and ACM (RR; 0.90 [CI, 0.83–0.97]) with no significant difference in subgroups <65 or ≥65 years. Additionally, GLP-1RAs reduced risk of MACE (10 %), ACM (12 %) and CV-death (12 %) with no significant difference in subgroups <75 or ≥75 years.

Four CVOTs (n = 33,063; 35–58 % ≥65 years) with DPP-4is were included. There were no significant differences in risk for CV outcomes with DPP-4is compared to placebo in any of the age subgroups.

Conclusion

The overall cardiovascular safety profile of newer anti-hyperglycemic agents is consistent in older and younger individuals.