A systematic review and meta-analysis of the impact of GLP-1 receptor agonists and SGLT-2 inhibitors on cardiovascular outcomes in biologically healthy older adults

Background: Unintentional weight loss is a hallmark of frailty and is associated with poor outcomes in older adults with type 2 diabetes. As such, the role of pharmacological therapies that facilitate weight loss - namely, sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists - remains uncertain in fitter older adults. We performed a systematic review and meta-analysis to evaluate these agents on major adverse cardiovascular events (MACE) in older adults eligible for participation in cardiovascular outcome trials. Methods: A literature search was performed in MEDLINE, EMBASE, CINAHL, Cochrane Central Registry of Controlled Trials (CENTRAL) and CNKI from inception to 29 June 2020. A class-specific meta-analysis was conducted in older adults (>65 years at recruitment) and compared with the similar analysis in younger (<65 years) adults. Results: Of 761 unique studies identified, nine met the criteria for inclusion, five using GLP-1 receptor agonists and four with SGLT-2 inhibitors. GLP-1 receptor agonists in older adults were associated with a 15.3% (OR 0.847 (95% CI 0.788 to 0.910)) reduction in MACE events, similar to the 16% benefit seen in younger adults. The use of SGLT-2 inhibitors reduced MACE in older participants by 16.9% (OR 0.831 (95% CI 0.699 to 0.989)), numerically superior to the impact in younger patients (OR 0.936 (95% CI 0.787 to 1.113). Conclusions: GLP-1 receptor agonists and SGLT-2 inhibitors reduced MACE outcomes in older adults who were eligible to participate in clinical trials. Whereas this is reassuring for the biologically robust, it should not be extrapolated to frail older adults without further investigation.

Automated summary

A systematic review and meta-analysis showed that GLP-1 receptor agonists and SGLT-2 inhibitors were effective in reducing major adverse cardiovascular events (MACE) in older adults eligible for clinical trials. The use of these medications in older adults demonstrated a similar or even superior benefit compared to younger individuals, indicating potential positive impacts in clinical practice.