Table 3. Characteristics of included studies.
MACEs: major adverse cardiovascular events; GLP-1 RA: glucagon-like peptide-1 receptor agonists; CVD: cardiovascular disease; CVOTs: cardiovascular outcome trials; SGLT-2: sodium-glucose cotransporter-2; RCTs: randomized controlled trials; T2DM: type 2 diabetes mellitus; CKD: chronic kidney disease; RR: relative risk; MI: myocardial infarction; eGFR: estimated glomerular filtration rate; HFpEF: heart failure with preserved ejection fraction; ASCVD: atherosclerotic cardiovascular disease; HbA1c: hemoglobin A1c.
| Author | Name of journal and publication year | Type of study | Patient population | Outcome |
| Alexander et al. [17] | Journal of General Internal Medicine, 2022 | Systematic review and meta-analysis | 45 trials comprising 71,517 patients were included | The three-component MACE outcome favored GLP-1 RA as compared to placebo (RR: 0.87, 95% CI: 0.82–0.93, I2 = 23%). GLP-1 RAs led to fewer strokes (RR: 0.86, 95% CI: 0.78–0.95, I2 = 0%). GLP-1 RAs compared to placebo were also associated with significant reductions in cardiovascular risk factors |
| D’Andrea et al. [18] | Cardiovascular Diabetology, 2020 | Systematic review and meta-analysis | 10 trials enrolling 89,790 patients were included | GLP-1 RA drugs showed a 12% overall reduction in MACEs (HR: 0.88; 95% CI: 0.82–0.94) |
| Giugliano et al. [19] | Cardiovascular Diabetology, 2021 | Meta-analysis | Eight CVOTs enrolling 60,080 patients were included of which 72.4% had established CVD | GLP-1 RAs reduce the risk of MACE by 14% compared to placebo in patients with T2DM over a period of 1.3-5.4 years (HR: 0.86; 95% CI: 0.79–0.94; P = 0.006) |
| Giugliano et al. [20] | Cardiovascular Diabetology, 2022 | Meta-analysis | 23 trials enrolling a total number of 181,143 participants were included | GLP-1 RA can reduce MACE by 13% and the risk of non-fatal stroke compared to placebo; SGLT-2 inhibitors are superior in reducing cardiovascular death, hospitalization for HF |
| Kanie et al. [21] | Cochrane Database of Systematic Reviews, 2021 | Meta-analysis | 20 RCTs enrolling 129,465 participants were included in meta-analysis (31 studies were used for qualitative analysis) | GLP-1 RA may lower the risk of CVD mortality and all-cause mortality in patients with established CVD, according to meta-analyses of moderate- to high-certainty evidence; moderate-certainty evidence is probable in favor of using GLP-1 RA to lower fatal and non-fatal stroke |
| Kelly et al. [22] | Pharmacotherapy, 2022 | Systematic review and meta-analysis | Four RCTs comprising 7130 patients with T2DM and CKD were included | In a subset population with T2DM and CKD, GLP-1 RAs were not linked with a lower risk of the composite cardiovascular endpoint (three-point composite MACE), compared to placebo (odds ratio: 0.80; 95% CI: 0.59–1.07; P = 0.13) |
| Liu et al. [23] | Frontiers in Cardiovascular Medicine, 2022 | Meta-analysis | Five RCTs with 31,314 patients, which had at least 30% patients with T2DM and MI, were included | GLP-1 RAs may be linked with reduced risk for atrial arrhythmias (RR: 0.81; 95% CI: 0.70–0.95).; GLP-1 RAs appear to have a stronger anti-atrial arrhythmia impact in patients with T2DM and MI |
| Qin et al. [24] | BMC Endocrine Disorders, 2022 | Meta-analysis | Six RCTs with a total of 52,821 patients were included | GLP-1 RA therapy reduced mortality from cardiovascular causes (RR: 0.90; 95% CI: 0.83–0.97; P = 0.004) and fatal or non-fatal stroke (RR: 0.85; 95% CI: 0.77–0.94; P = 0.001) |
| Sattar et al. [25] | Nature Medicine, 2022 | Meta-analysis | Seven RCTs with a total of 7215 patients | Participants with T2DM who took tirzepatide experienced no increased risk of serious cardiovascular problems across a spectrum of T2DM duration and cardiovascular risk levels (HR: 0.80; 95% CI: 0.57–1.11) |
| Wei et al. [26] | Frontiers in Endocrinology, 2022 | Systematic review and meta-analysis | Eight CVOTs were included with a total of 60,081 participants | GLP-1 RA therapy has no discernible impact on the risk of severe arrhythmias in T2DM patients (RR: 0.96; 95% CI: 0.96–1.05; P = 0.36) |
| Wei et al [27] | Frontiers in Endocrinology, 2022 | Meta-analysis | Eight RCTs with a total patient population of 60081 were included | GLP-1 RA significantly reduces the risk of total stroke (RR: 0.83; 95%CI: 0.73-0.95; P = 0.005), as well as ischemic stroke (RR: 0.83; 95%CI: 0.73-0.95; P = 0.008) in type 2 diabetes with cardiovascular risk factors |
| Yamada et al. [28] | Cardiovascular Diabetology, 2021 | Systematic review and meta-analysis | 13 studies were selected with a total of 32,949 patients | GLP-1 RAs did not lead to significantly lower cardiovascular endpoints in patients with T2DM and CKD (eGFR < 60 mL/min/1.73 m2) (RR: 0.91; 95% CI: 0.80–1.04) |
| Kreiner et al. [29] | Frontiers in Physiology, 2022 | Narrative review | Eight CVOTs with a total of 60,081 participants and one meta-analysis were included | People with HF who have or are at risk of having obesity-related HFpEF are most likely to benefit from GLP-1 RA therapy |
| Marx et al. [30] | Circulation, 2022 | Narrative review | Eight CVOTs with a total of 60,081 participants were included | Numerous studies have demonstrated that GLP-1 RAs lower cardiovascular risk in individuals with diabetes and ASCVD, or diabetes and high cardiovascular risk without regard to HbA1c |