Study summary · research use only
The efficacy and safety of danuglipron and orforglipron in patients with type 2 diabetes and obesity: a systematic review and meta-analysis
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This systematic review and meta-analysis (species not specified; human randomized controlled trials) searched PubMed, Web of Science, Cochrane Library, and Embase through 20 May 2025 for trials of danuglipron and orforglipron in type 2 diabetes (T2DM) and/or obesity. Eight studies with low bias risk, involving 1,454 participants, were analyzed. Danuglipron was associated with decreases in HbA1c (mean difference -0.90), fasting plasma glucose (-24.66), and weight (-2.17), and an increase in fasting plasma insulin (2.94). Orforglipron was associated with decreases in HbA1c (-1.02), fasting plasma glucose (-26.91), weight (-6.28), and BMI (-2.64). Both drugs were associated with treatment-related adverse events and gastrointestinal adverse events, and the authors call for further longitudinal study of their tolerability.
Abstract
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. 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. 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). 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.
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