SYSTEMATIC REVIEW article
Front. Endocrinol.
Sec. Clinical Diabetes
This article is part of the Research TopicExploring Combination Therapies for Effective Obesity and Metabolic Syndrome ManagementView all 3 articles
The efficacy and safety of danuglipron and orforglipron in patients with type 2 diabetes and obesity: a systematic review and meta-analysis
Provisionally accepted
- 1Fenyang College of Shanxi Medical University, Fenyang, China
- 2Fenyang Hospital of Shanxi Province, Fenyang, China
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Objective: This study assesses the efficacy and safety of the novel oral small molecule glucagon-like peptide-1 receptor agonists (GLP-1 RAs) danuglipron and orforglipron in the treatment of type 2 diabetes (T2DM) and obesity through systematic review and meta-analysis. Methods: Electronic databases (PubMed, Web of Science, Cochrane Library and Embase) were systematically searched up to 20 May 2025 to include randomised controlled trials evaluating danuglipron/orforglipron in patients with T2DM and/or obesity. Changes in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), fasting plasma insulin (FPI), weight and body mass index (BMI) compared with baseline post-treatment were evaluated using random-/fixed-effects models, alongside safety outcomes. Results: Eight studies with low bias risk involving 1,454 participants were analysed. Meta-analysis results demonstrated that danuglipron significantly decreased HbA1c (mean difference [MD]: −0.90; 95% CI: −1.06, −0.74), FPG (MD: −24.66; 95% CI: −30.45, −18.86) and weight (MD: −2.17; 95% CI: −3.10, −1.23) and improved FPI (MD: 2.94; 95% CI: 1.50, 4.38). Orforglipron also showed significant positive effects on HbA1c (MD: −1.02; 95% CI: −1.18, −0.86), FPG (MD: −26.91; 95% CI: −31.05, −22.78), weight (MD: −6.28; 95% CI: −8.45, −4.11) and BMI (MD: −2.64; 95% CI: −3.38, −1.89). However, both danuglipron and orforglipron were associated with the occurrence of treatment-related adverse events and gastrointestinal adverse events (AEs). Conclusion: The oral GLP-1 RAs danuglipron and orforglipron are capable of improving blood glucose levels and reducing weight; however, they also pose an increased risk of gastrointestinal AEs. Further longitudinal studies are warranted to gain a deeper understanding of their efficacy, safety and tolerability.
Keywords: efficacy, Danuglipron, Orforglipron, Type 2 diabetes and obesity, Meta-analysis
Received: 14 Jun 2025; Accepted: 03 Nov 2025.
Copyright: © 2025 Zhou, Wang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jingjing Zhou, zhoujingjing_zjjz@163.com
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