Efficacy and safety of glucagon-like peptide-1 agonists on macrovascular and microvascular events in type 2 diabetes mellitus: A meta-analysis

• Published in: Nutrition, metabolism, and cardiovascular diseases Vol. 27; no. 12; pp. 1081 - 1088
• Main Authors: Gargiulo, P., Savarese, G., D'Amore, C., De Martino, F., Lund, L.H., Marsico, F., Dellegrottaglie, S., Marciano, C., Trimarco, B., Perrone-Filardi, P.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2017
• Subjects: Cardiovascular events; Diabetes mellitus; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - mortality; Diabetic Angiopathies - blood; Diabetic Angiopathies - etiology; Diabetic Angiopathies - mortality; Diabetic Angiopathies - prevention & control; Glucagon-Like Peptide 1 - agonists; Glucagon-Like Peptide 1 - metabolism; Humans; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Incretins - adverse effects; Incretins - therapeutic use; Macrovascular events; Medicin och hälsovetenskap; Microvascular events; Nephropathy; Retinopathy; Risk Assessment; Risk Factors; Signal Transduction - drug effects; Treatment Outcome; Macrovascular events; Cardiovascular events; Retinopathy; GLP-1; Diabetes mellitus; DPP-4; DM; Microvascular events; CIs; RRs; Nephropathy; CV; MI; HbA1c; HF; Glucagon-like peptide-1 agonists
• ISSN: 0939-4753; 1590-3729; 1590-3729
• DOI: 10.1016/j.numecd.2017.09.006

Glucagon-like peptide-1 (GLP-1) agonists improve glycaemic control in type 2 diabetes mellitus (DM). Outcome trials investigating macro and microvascular effects of GLP-1 agonists reported conflicting results. The aim of this study was to assess, in a meta-analysis, the effects of GLP-1 agonists on mortality, major nonfatal cardiovascular (CV) events, renal and retinal events. MEDLINE, Cochrane, ISI Web of Science, SCOPUS and ClinicalTrial.gov databases were searched for articles published until June 2017. Randomized trials enrolling more than 200 patients, comparing GLP-1 versus placebo or active treatments in patients with DM, and assessing outcomes among all-cause death, CV death, MI, stroke, HF, diabetic retinopathy and nephropathy were included. 77 randomized trials enrolling 60,434 patients were included. Compared to control, treatment with GLP-1 significantly reduced the risk of all-cause death (RR: 0.888; CI: 0.804–0.979; p = 0.018) and the risk of CV death (RR: 0.858; CI: 0.757–0.973; p = 0.017). 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). Treatment with GLP-1 agonists in DM patients is associated with a significant reduction of all cause and CV mortality. •GLP-1 agonists have a safe cardiovascular profile.•Treatment with GLP-1 agonists is associated with a significant reduction of all-cause mortality and of CV mortality.•The differences in efficacy in HbA1c lowering between GLP-1 agonists and control did not impact on differences in all-cause death and CV death.•The significant increased risk of retinopathy associated with more severe reduction of HbA1c need to be assessed in future studies.