GLP-1 agonists on the other hand, showed significant reduction in MACE (RR 0.92; 95% CI 0.87-0.97), death from CV causes (RR=0.88; 95% CI 0.80-0.97), and death from any cause (RR=0.89; 95% CI 0.82-0.96).
The LEADER and SUSTAIN-6 trials evaluating the safety and efficacy of the GLP-1 analogs liraglutide and semaglutide, respectively, showed a statistically significant reduction in the primary outcome (major adverse cardiac events [MACE]: CV death, myocardial infarction, and stroke) and the secondary combined outcome when compared to placebo.
We searched the PubMed, Embase, and Google scholar databases, combining the term "glucagon-like peptide 1" OR "GLP-1" OR "incretin" OR "liraglutide" OR "exenatide" OR "lixisenatide" OR "dulaglutide" OR "albiglutide" AND "inpatient" OR "hospital" OR "perioperative" OR "postoperative" OR "surgery" OR "myocardial infarction" OR "stroke" OR "cerebrovascular disease" OR "transient ischaemic attack" OR "ICU" OR "critical care" OR "critical illness" OR "CCU" OR "coronary care unit."
Shortly thereafter, the injectable glucagon-like peptide agonists (GLP-1) liraglutide and semaglutide found a significant reduction in composite major cardiovascular events (CV death, non-fatal MI, or stroke).
Proglucagon-derived peptides, especially glucagon-like peptide-1 (GLP-1) and its long-acting mimetics, have exhibited neuroprotective effects in animal models of stroke.
GLP-1 agonists did not affect the risk of MI (RR: 0.917; CI: 0.830-1.014; p = 0.092) as well as the risk of stroke (RR: 0.882; CI: 0.759-1.023; p = 0.097), HF (RR: 0.967; CI: 0.803-1.165; p = 0.725), retinopathy (RR: 1.000; CI: 0.807-1.238; p = 0.997) and nephropathy (RR: 0.866; CI: 0.625-1.199; p = 0.385).
Previous research has demonstrated that GLP-1 analogs are neuroprotective in several neurological disease models including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke.
In comparison, GLP-1 RA appear to preferentially reduce ischemic events (stroke or myocardial infarction) over hospitalization for heart failure, and demonstrated renoprotection in several of the CVOTs.
SGLT2i and GLP-1 RA may have a synergic effect on glucose reduction, weight reduction, renal impairment (both an independent lethal disease and a CVD risk factor) improvement, and cardiac event reduction, because the first reduces HF and related events and the second decreases CVD risk (mainly MI and stroke).