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Efficacy and Safety of Orforglipron in Obese Adults With or Without Diabetes: A Systematic Review and Meta-Analysis.
Endocrinol Diabetes Metab · 2025
Last updated 2026-05-28A review of five studies with 4,410 participants found that orforglipron, a new oral GLP-1 drug, reduced body weight by 2.48% to 9.8% depending on the dose (3 mg to 45 mg). It also improved blood sugar control (HbA1c) by 0.76% to 1.04% and lowered cholesterol and triglycerides, but higher doses (12 mg or more) caused more stomach-related side effects and led to more people stopping treatment.
AI summary of the abstract below.
| Journal | Endocrinol Diabetes Metab, 2025 |
|---|---|
| Citations | 3 |
| Molecules | orforglipron |
| Conditions studied | Type 2 Diabetes, Obesity |
Abstract
BACKGROUND: Obesity represents a major global health challenge, contributing substantially to cardiovascular disease and metabolic complications. Orforglipron, a novel oral non-peptide GLP-1 receptor agonist, has emerged as a promising therapeutic option for weight management and glycemic control. This meta-analysis evaluated the efficacy and safety of orforglipron in obese patients with or without type 2 diabetes mellitus (T2DM).
METHODS: A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library and ClinicalTrials.gov from inception to October 2025 to identify randomised controlled trials (RCTs) evaluating orforglipron in obese patients. Mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models.
RESULTS: Five RCTs comprising 4410 participants were included. Orforglipron demonstrated dose-dependent reductions in body weight from 2.48% at 3 mg to 9.8% at 45 mg, BMI from 0.89 to 3.62 kg/m, waist circumference from 1.57 to 6.9 cm, and HbA1c from 0.76% to 1.04% compared with placebo. Favourable lipid changes included reductions in total cholesterol (MD: -4.51% [95% CI: -6.91 to -2.11]), LDL-C (MD: -5.34% [95% CI: -7.10 to -3.58]), and triglycerides (MD: -10.07% [95% CI: -12.33 to -7.80]), with increased HDL-C (MD: 2.94% [95% CI: 1.38 to 4.49]). However, gastrointestinal adverse events were significantly more frequent at doses of 12 mg or higher and treatment discontinuation rates were highest at 24 mg (RR:4.61 [95% CI:1.6 to 13.33]) and 36 mg (RR:3.68 [95% CI:2.48 to 5.44]) doses. Serious adverse events and mortality rates were comparable to those with placebo.
CONCLUSION: Orforglipron significantly improved glycemic and lipid parameters in patients with obesity, demonstrating dose-dependent efficacy with maximal benefits at higher doses. While gastrointestinal tolerability remains a clinically important limitation requiring mitigation strategies, orforglipron represents a promising oral therapeutic option for comprehensive obesity and metabolic management.
Verbatim abstract via PubMed 41296780 ↗
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