Abstract

Type 2 diabetes mellitus (T2DM) was characterized by hyperglycemia and frequently accompanied by obesity and 
elevated cardiovascular risk. Incretin hormone-based therapies, especially glucagon-like peptide-1 receptor agonists 
(GLP-1 RAs), had demonstrated efficacy in glycemic control, weight reduction, and cardiovascular risk mitigation. 
Recently, dual agonists targeting both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors 
had emerged as promising therapeutic agents aiming to enhance these benefits. This review assessed the efficacy 
and safety of dual GLP-1/GIP agonists specifically regarding weight reduction and cardiovascular outcomes in 
patients with T2DM. A systematic literature search was conducted, prioritizing randomized controlled trials, meta
analyses, and high-quality observational studies published within the last decade on dual GLP-1/GIP agonists in 
T2DM management. Dual GLP-1/GIP receptor agonists produced superior weight loss and glycemic control 
compared to GLP-1 monoagonists, attributable to complementary incretin receptor signaling that enhances insulin 
secretion, suppresses glucagon, and reduces appetite. Cardiovascular outcome trials demonstrated noninferiority to 
established GLP-1 RAs and suggest potential additional cardioprotective effects, although evidence for superiority 
remains inconclusive. These dual agonists also exerted beneficial effects on risk factors such as lipid profiles and 
blood pressure. However, data heterogeneity and evolving trial designs merit cautious interpretation. Dual GLP
1/GIP agonists represented a significant advance in T2DM treatment, offering enhanced weight reduction and 
promising cardiovascular benefits. Further large-scale and long-term studies are warranted to fully characterize 
their cardiovascular protective profile and optimize clinical application.