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
This is the final version. Available on open access from BJDVD Ltd via the DOI in this recordBackground: 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, sodiumglucose co-transporter-2 (SGLT-2) inhibitors and glucagonlike 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.National Institute for Health Research (NIHR
