Efpeglenatide, a novel long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), shows promise for the treatment of type 2 diabetes mellitus (T2DM) and obesity. This systematic review evaluated the efficacy and safety of efpeglenatide in patients with T2DM and obesity. Literature searches in PubMed, Scopus, and Web of Science focused on randomized controlled trials (RCTs), cohort studies, case-control studies, and longitudinal observational studies from 2019 to 2024. Eight studies met the inclusion criteria. The findings of these studies consistently indicate that efpeglenatide significantly reduces hemoglobin A1C (HbA1C), fasting plasma glucose (FPG), and body weight in patients with T2DM and obesity. Once-weekly dosing offers a convenient alternative to daily GLP-1 RAs and potentially improves adherence. Efpeglenatide also provides cardiovascular and renal benefits, particularly for high-risk patients, thus providing a comprehensive treatment option. The safety profile is similar to that of other GLP-1 RAs, with mild-to-moderate gastrointestinal side effects being the most common and a low risk of hypoglycemia, especially in patients not using insulin or sulfonylureas. Most studies show a low risk of bias and enhanced reliability. However, limitations include the need for long-term safety data and variations in study design. Future research should focus on cardiovascular outcomes, long-term safety, and improvements in quality of life to fully assess the benefits of efpeglenatide. In conclusion, efpeglenatide is a promising treatment for T2DM and obesity, offering effective glycemic control, weight reduction, cardiovascular and renal benefits, a favorable safety profile, and convenient dosing.
