# GLP-1 receptor agonists (drug class) Drug · id `cardio:glp1-receptor-agonists` · Cardiovascular Atlas · release `f6f6f1b6f50379ed` (public) > General information from published sources, not medical advice, and not reviewed by clinicians. Check the cited source before relying on anything here. The atlas's own text and curation may be reused under Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0, https://creativecommons.org/licenses/by-nc/4.0/): credit the atlas, and do not use it commercially. See the atlas About page. Text quoted from a source stays under that source's own terms, given as the source's reuse\_basis. The atlas's reuse terms do not cover it. The downloads list each quotation with its source in third\_party\_quotations. Also called: GLP-1 receptor agonists; GLP-1 RAs; Glucagon-like peptide-1 receptor agonists Browse, organ or system: Metabolism Browse, condition area: Diabetes and metabolic disease ## In plain language A group of diabetes medicines called GLP-1 receptor agonists. Some are given as a weekly injection. Large trials in people with type 2 diabetes asked whether they lower the chance of heart attack, stroke and heart-related death, and one trial asked the same question in people who had heart disease and obesity but no diabetes. ## Technical summary Class record joining the cardiovascular outcome trials of GLP-1 receptor agonists. A 2018 meta-analysis of ELIXA, LEADER, SUSTAIN 6 and EXSCEL found a 10 percent lower risk of three-point major adverse cardiovascular events (hazard ratio 0.90, 95% CI 0.82 to 0.99). Semaglutide and tirzepatide are members by the established pharmacologic class listed in RxClass. SELECT tested semaglutide in people without diabetes; SURPASS-CVOT compared tirzepatide with dulaglutide. ## Claims, with the population each applies to ## Context: Adults with type 2 diabetes in four GLP-1 receptor agonist cardiovascular outcome trials (ELIXA, LEADER, SUSTAIN 6, EXSCEL) Recipient: Adult; Population: Adults aged 18 years or older with type 2 diabetes, in randomized trials that compared a GLP-1 receptor agonist with placebo and had a primary outcome that included cardiovascular death, nonfatal myocardial infarction and nonfatal stroke.; Care setting: Not stated in the abstract; Geography: Not stated in the abstract; Life stage: Adults aged 18 years or older; Follow-up: Not stated for the pooled analysis. The literature search ran up to 18 September 2017. ### A 2018 meta-analysis pooled four cardiovascular outcome trials of GLP-1 receptor agonists in adults with type 2 diabetes: ELIXA (lixisenatide), LEADER (liraglutide), SUSTAIN 6 (semaglutide) and EXSCEL (extended-release exenatide). Compared with placebo, the drugs lowered the risk of the three-point major adverse cardiovascular event outcome (cardiovascular death, nonfatal heart attack or nonfatal stroke) by 10 percent (hazard ratio 0.90, 95% CI 0.82 to 0.99; p=0.033). Cardiovascular death was 13 percent lower (0.87, 0.79 to 0.96) and death from any cause 12 percent lower (0.88, 0.81 to 0.95). The authors found no significant effect on fatal and non-fatal heart attack, fatal and non-fatal stroke, hospital admission for unstable angina, or hospital admission for heart failure. They also found no significant differences in severe hypoglycaemia, pancreatitis, pancreatic cancer or medullary thyroid cancer. - Category: Effect - Evidence stage: Evidence synthesis - Certainty: Certainty not assessed - Applies to: Recipient: Adult; Population: Adults aged 18 years or older with type 2 diabetes, in randomized trials that compared a GLP-1 receptor agonist with placebo and had a primary outcome that included cardiovascular death, nonfatal myocardial infarction and nonfatal stroke.; Care setting: Not stated in the abstract; Geography: Not stated in the abstract; Life stage: Adults aged 18 years or older; Follow-up: Not stated for the pooled analysis. The literature search ran up to 18 September 2017. - Limitations: A pooled analysis of published trials of four different drugs, not of one drug. The abstract says the benefit varied to varying degrees between individual drugs and that between-trial heterogeneity was low to moderate. The search ran only up to 18 September 2017, so later trials, such as SELECT and SURPASS-CVOT in this atlas, are not in it. The abstract names the funding as Amylin Pharmaceuticals (AstraZeneca). The abstract does not grade certainty. Only the PubMed abstract was read. - Last checked: 2026-10-14 - Sources: 1. Supports: Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) Locator: Abstract, FINDINGS, sentence 1. Retrieved 2026-10-14T18:18:50Z. Source state: Current. Snapshot hash: dcf556409b960c64a25ada11dce3bb914295a33577ab5cd400516c6b2657fc85. How it applies: The four trials the meta-analysis found. 2. Supports: Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) Locator: Abstract, FINDINGS, sentence 2. Retrieved 2026-10-14T18:18:50Z. Source state: Current. Snapshot hash: dcf556409b960c64a25ada11dce3bb914295a33577ab5cd400516c6b2657fc85. How it applies: Pooled hazard ratios for the three-point MACE outcome, cardiovascular death and all-cause death. 3. Supports: Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) Locator: Abstract, FINDINGS, sentence 3. Retrieved 2026-10-14T18:18:50Z. Source state: Current. Snapshot hash: dcf556409b960c64a25ada11dce3bb914295a33577ab5cd400516c6b2657fc85. How it applies: Outcomes with no significant effect. 4. Supports: Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) Locator: Abstract, FINDINGS, sentence 4. Retrieved 2026-10-14T18:18:50Z. Source state: Current. Snapshot hash: dcf556409b960c64a25ada11dce3bb914295a33577ab5cd400516c6b2657fc85. How it applies: Safety outcomes with no significant difference. 5. Supports: Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) Locator: Abstract, INTERPRETATION, sentence 1; Abstract, INTERPRETATION, sentence 2. Retrieved 2026-10-14T18:18:50Z. Source state: Current. Snapshot hash: dcf556409b960c64a25ada11dce3bb914295a33577ab5cd400516c6b2657fc85. How it applies: The authors interpretation, including variation between individual drugs. 6. Background: Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) Locator: Abstract, METHODS, sentence 1; Abstract, METHODS, sentence 2; Abstract, METHODS, sentence 3. Retrieved 2026-10-14T18:18:50Z. Source state: Current. Snapshot hash: dcf556409b960c64a25ada11dce3bb914295a33577ab5cd400516c6b2657fc85. How it applies: Eligible trials and the search date. 7. Background: Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.) Locator: Abstract, FUNDING, sentence 1. Retrieved 2026-10-14T18:18:50Z. Source state: Current. Snapshot hash: dcf556409b960c64a25ada11dce3bb914295a33577ab5cd400516c6b2657fc85. How it applies: Funding line in the abstract. ## Connected pages - A pooled analysis of four outcome trials looked at major cardiovascular events: Type 2 diabetes (`cardio:type-2-diabetes`) [a claim, not a settled fact; see claim `cardio:claim-glp1-ra-meta-analysis-mace` and its context] - Filed under this front: Medicines (`cardio:front-medicines`) - Has subtype: Semaglutide (`cardio:semaglutide`) - Has subtype: Tirzepatide (`cardio:tirzepatide`) - Investigated in: LEADER: liraglutide and cardiovascular events in type 2 diabetes (`cardio:leader-trial`) ## Provenance Content hash: c6139e90658c3311cb956a682c94d1c12c58bf38b0ccfeaa834de4782a902461 Last substantive edit: 2026-10-15 Evidence last checked: Not recorded