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Study 28 of 28Orforglipron (LY-3502970) literatureThe Annals of pharmacotherapy · RCT · Phase 2

Orforglipron: An Oral GLP-1 Receptor Agonist for Obesity Treatment.

Orforglipron shows a mean placebo-adjusted weight reduction of 7.1% to 10.6%, but further research is needed to assess its efficacy for obesity-related comorbidities.

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Where it sits

this study against the rest of the orforglipron (ly-3502970) corpus
8
Preclinical
6
Observational
1
Open-label
6
Randomised · this one
7
Reviews

Summary and findings

This study evaluates the properties of orforglipron, an oral glucagon-like peptide-1 receptor agonist, for obesity treatment. The analysis includes data from two phase 1 studies and four phase 2/3 clinical trials. Findings indicate a mean placebo-adjusted weight reduction of 7.1% to 10.6% with orforglipron.

How much of this paper we could read: full text read (0.70). We had a clear abstract, so the summary below closely tracks the paper. What this means →
mean 7.1% to 10.6% placebo-adjusted weight reduction with orforglipronPhase 2

Abstract

The authors’ words, as The Annals of pharmacotherapy supplied them

<h4>Objective</h4>To describe the properties of a newly approved oral glucagon-like peptide-1 receptor agonist for the treatment of obesity.<h4>Data sources</h4>A literature search of MEDLINE and SCOPUS was performed without date range exclusions using the search terms orforglipron and obesity. Additional articles were identified from review of clinical trial bibliographies and product monograph.<h4>Study selection and data extraction</h4>Two phase 1 studies in healthy individuals and in patients with type 2 diabetes mellitus and 4 phase 2/3 clinical trials specifically evaluating orforglipron use for obesity were identified for analysis, using no date exclusion criteria.<h4>Data synthesis</h4>Orforglipron was evaluated in 4 phase 2/3 trials regarding its efficacy for weight loss. These trials showed a mean 7.1% to 10.6% placebo-adjusted weight reduction with orforglipron. Adverse events seen with its use were primarily gastrointestinal.Relevance to Patient Care and Clinical Practice in Comparison With Existing Drugs:Orforglipron provides an oral weight management option that is potentially more effective than liraglutide, similarly effective compared with semaglutide, and less effective than tirzepatide. As a non-injectable option that does not require strict oral administration parameters, orforglipron has advantages in certain patient populations.<h4>Conclusions</h4>Orforglipron is a potentially useful addition for the treatment of obesity, but it still requires additional data on efficacy in treatment of obesity-related comorbidities for full comparison.

Background

This paper addresses the properties of orforglipron, a newly approved oral GLP-1 receptor agonist for obesity treatment. Prior to this, injectable GLP-1 receptor agonists like liraglutide and semaglutide were the primary options for weight management. Understanding the efficacy and safety of orforglipron is important as it may offer a non-injectable alternative for patients.

Methods

The study involved a literature search of MEDLINE and SCOPUS for phase 1 and phase 2/3 trials evaluating orforglipron. Two phase 1 studies included healthy individuals and patients with type 2 diabetes mellitus. Four phase 2/3 trials specifically assessed the efficacy of orforglipron for obesity treatment.

Results

The trials showed a mean placebo-adjusted weight reduction of 7.1% to 10.6% with orforglipron. Adverse events were primarily gastrointestinal but specific rates were not reported in the abstract.

Interpretation

The weight reduction observed with orforglipron is statistically significant; however, the clinical significance may vary based on individual patient contexts. Compared to existing treatments, orforglipron may be more effective than liraglutide and similarly effective as semaglutide, but less effective than tirzepatide. Limitations include reliance on phase 2/3 trials which may not provide comprehensive long-term data.

Key findings

  • mean 7.1% to 10.6% placebo-adjusted weight reduction with orforglipron
  • Not reported in abstract.

Limitations

  • data from phase 1 and phase 2/3 trials only
  • small sample sizes may limit generalizability
  • adverse event rates not fully detailed
  • lack of long-term efficacy data

Elsewhere in the Orforglipron (LY-3502970) corpus

BGLP-1 receptor agonists and ocular safety- Pharmacokinetic insights into ischemic optic neuropathy and diabetic retinopathy risk: A review.Biomolecules & biomedicine · 2026 · Hazard ratios for NAION ranged from 1.29 to 7.64.reviewAEfficacy and safety of orforglipron 12 mg versus orforglipron 36 mg maintenance dose among patients with obesity with or without diabetes: a systematic review and comprehensive meta-analysis.BMC endocrine disorders · 2026 · n=3459 · Percentage body weight change p < 0.00001.reviewAPredicting the Long-Term Risk of Type 2 Diabetes and Cardiovascular Disease With Orforglipron in People With Overweight or Obesity: A Post Hoc Analysis of the ATTAIN-1 Trial.Diabetes, obesity & metabolism · 2026 · -48.6% to -59.4% relative reduction in T2D risk score vs placebo (-10.5%; p<0.0001; HR-range 0.43-0.55)HumanDOrforglipron and the Kidney: A Promise or Disappointment? The Need for Trials Examining Renal Outcomes.American journal of nephrology · Not reported in abstract.reviewBExploratory Cardiovascular Risk Modeling of Orforglipron Using the PREVENT Equations Compared with the Pooled Cohort Equations: A Post-Hoc Analysis from a Systematic Review and Meta-analysis.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2023 · For a representative 50-year-old man with T2D at the 36 mg dose, PCE estimated a 10-year RRR of 16.8%, while PREVENT projected an RRR of 31.4%.reviewCVariant-specific pharmacophoric shifts in glucagon-like peptide-1 receptor-orforglipron complexes revealed by Boltz-2 co-folding and membrane molecular dynamics.International journal of biological macromolecules · 2026 · G168S exhibited the strongest binding (-117.18 kcal/mol)In vitro