Pair page
Orforglipron with Semaglutide
Mechanism-tag overlap and published literature for Orforglipron and Semaglutide, pulled verbatim from each Kalios compound profile. Kalios is a literature reference, not a recommendation.
Mechanism overlap
Mechanism tags are verbatim labels on each compound's profile. Generic tags ("peptide", "small-molecule", "research-chemical") are excluded from this overlap view. Tags are descriptive — not an inference about combined effect.
oral-non-peptide-glp-1-receptor-agonist
glp-1-receptor-agonistmetabolic
Co-administration notes from the literature
Verbatim summary text pulled from each compound's profile data. Researchers studying Orforglipron and Semaglutide have published these mechanism-level observations. Not a co-administration recommendation.
Do not combine. Both are GLP-1 RA class (tirzepatide is GLP-1 / GIP dual). Use of orforglipron plus an injectable GLP-1 or dual agonist is pharmacodynamically duplicative and increases AE burden without additional benefit.
Quick facts
Orforglipron
Semaglutide
Literature table
Classified references from each compound profile. Click a column header to sort. Click a PMID to open PubMed. Findings are quoted verbatim from each profile's literature_summary; nothing here is added or interpreted.
| Year | Compound | Source | Finding |
|---|---|---|---|
| 2025 | Orforglipron | Wharton S, Aronne LJ, Stefanski A, Pratt E, Liu R, Hayes PS, Ahmad NN, Li B, Fernández Landó L, Nunes M, et al. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. N Engl J Med. 2025. DOI: 10.1056/NEJMoa2511774 (ATTAIN-1, 72-week Phase 3 obesity). | human trial, Phase 3 |
| 2025 | Orforglipron | Eli Lilly and Company. Lilly's oral GLP-1, orforglipron, is successful in third Phase 3 trial (ATTAIN-2), triggering global regulatory submissions this year for the treatment of obesity. Press release, Aug 26 2025. | human trial, Phase 3 |
| — | Orforglipron | ClinicalTrials.gov. ACHIEVE-1 (NCT05971940); ATTAIN-1 (NCT05869903); ATTAIN-2 and related Phase 3 protocols under the orforglipron program. | human trial, Phase 3 |
| 2023 | Orforglipron | Frias JP, Hsia S, Eyde S, Liu R, Ma X, Konig M, Kazda C, Mather KJ, Haupt A, Pratt E, Robins D, Pyrah I, Hartman ML, Bumol TF. Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study. Lancet. 2023;402(104… PMID 37369232 | human trial, Phase 2 |
| 2025 | Orforglipron | Rosenstock J, Hsia S, Nevarez Ruiz L, Eyde S, Cox D, Wu WS, Liu R, Li J, Fernández Landó L, Denning M, Ludwig L, Chen Y; ACHIEVE-1 Trial Investigators. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes. N Engl J Med. 2025;393(11):1001-1013. PM… PMID 40544435 | human trial |
| 2023 | Orforglipron | Pratt E, Ma X, Liu R, Robins D, Coskun T, Sloop KW, Haupt A, Benson C. Orforglipron (LY3502970), a novel, oral non-peptide glucagon-like peptide-1 receptor agonist: A Phase 1b, multicentre, blinded, placebo-controlled, randomized, multiple-ascending-dose study in people with typ… PMID 37264711 | human trial, Phase 1 |
| 2023 | Orforglipron | Pratt E, Ma X, Liu R, Robins D, Haupt A, Coskun T, Sloop KW, Benson C. Orforglipron (LY3502970), a novel, oral non-peptide glucagon-like peptide-1 receptor agonist: a phase 1a, blinded, placebo-controlled, randomized, single- and multiple-ascending-dose study in healthy particip… PMID 37264690 | human trial, Phase 1 |
| 2023 | Orforglipron | Wharton S, Blevins T, Connery L, Rosenstock J, Raha S, Liu R, Ma X, Mather KJ, Haupt A, Robins D, Pratt E, Kazda C, Konig M; GZGI Investigators. Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. N Engl J Med. 2023;389(10):877-888. PMID: 37342912. PMID 37342912 | human study |
| 2022 | Orforglipron | Chow E, Yang A, Chung CHL, Chan JCN. A Clinical Perspective of the Multifaceted Mechanism of Metformin in Diabetes, Infections, Cognitive Dysfunction, and Cancer. Pharmaceuticals (Basel). 2022;15(4):442. PMID: 35455439. (Companion metformin pharmacology context for T2D combinati… PMID 35455439 | review |
| 2024 | Orforglipron | Ma X, Liu R, Pratt EJ, Benson CT, Bhattachar SN, Sloop KW. Effect of Food Consumption on the Pharmacokinetics, Safety, and Tolerability of Once-Daily Orally Administered Orforglipron (LY3502970), a Non-peptide GLP-1 Receptor Agonist. Diabetes Ther. 2024;15(4):819-832. PMID: 3834… PMID 38349475 | research article |
| 2020 | Orforglipron | Kawai T, Sun B, Yoshino H, Feng D, Suzuki Y, Fukazawa M, Nagao S, Wainscott DB, Showalter AD, Droz BA, Kobilka TS, Coghlan MP, Willard FS, Kawabe Y, Kobilka BK, Sloop KW. Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist. Proc Natl… PMID 33177239 | research article |
| 2024 | Semaglutide | Perkovic V, Tuttle KR, Rossing P, et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes (FLOW). N Engl J Med. 2024;391(2):109-121. PMID: 38785209. PMID 38785209 | human trial |
| 2023 | Semaglutide | Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). N Engl J Med. 2023;389(24):2221-2232. PMID: 37952131. PMID 37952131 | human trial |
| 2022 | Semaglutide | Garvey WT, Batterham RL, Bhatta M, et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med. 2022;28(10):2083-2091. PMID: 36216945. PMID 36216945 | human trial |
| 2022 | Semaglutide | Rubino DM, Greenway FL, Khalid U, et al. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes (STEP 8). JAMA. 2022;327(2):138-150. PMID: 35015037. PMID 35015037 | human trial |
| 2021 | Semaglutide | Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021;384(11):989-1002. PMID: 33567185. PMID 33567185 | human trial |
| 2021 | Semaglutide | Davies M, Færch L, Jeppesen OK, et al. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2). Lancet. 2021;397(10278):971-984. PMID: 33667417. PMID 33667417 | human trial |
| 2021 | Semaglutide | Wadden TA, Bailey TS, Billings LK, et al. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity (STEP 3). JAMA. 2021;325(14):1403-1413. PMID: 33625476. PMID 33625476 | human trial |
| 2021 | Semaglutide | Rubino D, Abrahamsson N, Davies M, et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity (STEP 4). JAMA. 2021;325(14):1414-1425. PMID: 33755728. PMID 33755728 | human trial |
| 2021 | Semaglutide | Newsome PN, Buchholtz K, Cusi K, et al. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. N Engl J Med. 2021;384(12):1113-1124. PMID: 33185364. PMID 33185364 | human trial |
| 2019 | Semaglutide | Aroda VR, Rosenstock J, Terauchi Y, et al. PIONEER 1: Randomized Clinical Trial of the Efficacy and Safety of Oral Semaglutide Monotherapy in Comparison With Placebo in Patients With Type 2 Diabetes. Diabetes Care. 2019;42(9):1724-1732. PMID: 31186300. PMID 31186300 | human trial |
| 2016 | Semaglutide | Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN 6). N Engl J Med. 2016;375(19):1834-1844. PMID: 27633186. PMID 27633186 | human trial |
| 2019 | Semaglutide | Knudsen LB, Lau J. The Discovery and Development of Liraglutide and Semaglutide. Front Endocrinol. 2019;10:155. PMID: 31031702. PMID 31031702 | mechanism / discovery |
Related pair pages
More research context
Frequently asked
Have Orforglipron and Semaglutide been studied together?
Researchers have published mechanistic-level co-administration discussion of Orforglipron and Semaglutide. No human co-administration trials are catalogued in the Kalios profiles. The pair page lists each compound's classified literature; full citations sit on each individual profile.
What mechanisms do Orforglipron and Semaglutide share?
Orforglipron and Semaglutide do not share a specific mechanism tag on their Kalios profiles. They appear on the same pair page because at least one profile lists the other in its co-administration data.
What is the FDA status of Orforglipron and Semaglutide?
Orforglipron: Under review (submissions late 2025). Semaglutide: Approved (2017). FDA-status text is pulled verbatim from each compound profile. See /fda-pcac-2026.html for the broader FDA Pharmacy Compounding Advisory Committee context.
Where can I find the full research on Orforglipron and Semaglutide?
Full citation lists, dosing tables from the literature, reconstitution data, and the FDA / WADA status are on the individual compound profiles: the Orforglipron profile and the Semaglutide profile. The Kalios Stack Research Tool hub lists every compound covered.
Last updated: April 2026