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Metabolic and Glycemic Effects of Orforglipron, a GLP-1 Receptor Agonist, in Adults With or Without Diabetes: A

Ahmed W Hageen1, Ahmed Farid Gadelmawla2,3, Ahmad Omar Saleh4

  • 1Faculty of Medicine, Tanta University, Tanta, Egypt.

Endocrinology, Diabetes & Metabolism
|July 23, 2026
PubMed
Abstract

Insights

Orforglipron (OFG), an oral GLP-1 RA, effectively reduces weight and improves glycemic control in adults. Higher doses show greater benefits, though adverse events increase with dose.

Area of Science:

  • Pharmacology
  • Metabolic Diseases
  • Clinical Trials

Background:

  • Orforglipron (OFG) is an oral, non-peptide glucagon-like peptide-1 receptor agonist (GLP-1 RA).
  • OFG shows promise for type 2 diabetes mellitus (T2DM) and obesity management.
  • Dose-response effects of OFG require further analysis.

Purpose of the Study:

  • To conduct a network meta-analysis of OFG's dose-response effects.
  • To evaluate OFG's impact on body weight and glycemic outcomes.
  • To analyze data across multiple OFG doses (3-45 mg) at various time points (12, 26, 36 weeks).

Main Methods:

  • Adherence to PRISMA guidelines.
  • Systematic literature search of Embase, PubMed, Web of Science, and Scopus for randomized controlled trials (RCTs).
  • Random-effects models used to express efficacy (OR, MD, SMD) with 95% confidence intervals (CI).

Main Results:

  • Six RCTs with 4878 participants were included.
  • OFG significantly reduced body weight, BMI, and waist circumference across all doses and follow-ups.
  • The 45 mg dose yielded the most substantial weight loss (MD: -12.13 kg at 36 weeks).
  • Significant improvements in HbA1c and fasting glucose were observed, with dose-dependent effects.
  • Treatment-emergent adverse events increased with higher OFG doses.

Conclusions:

  • OFG effectively improves weight-related and glycemic outcomes in adults.
  • Dose escalation of OFG leads to greater efficacy but also increased adverse events.
  • Findings support OFG's potential as an oral therapeutic option for T2DM and obesity.
Keywords:
HbA1cbody weightglucagon‐like peptide‐1 receptor agonistsobesityorforglipron

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