Orforglipron Research & Scientific Overview

Jump to: Structure | Mechanism | Studies | Pharmacokinetics | Protocols | Limitations | Lead Researcher | References

Orforglipron Molecular Structure & Chemical Properties

Orforglipron represents a groundbreaking advancement in metabolic disease pharmacotherapy as the first oral, nonpeptide small-molecule glucagon-like peptide-1 receptor agonist to reach advanced clinical development. Originally discovered by Chugai Pharmaceutical Co., Ltd. and licensed to Eli Lilly and Company in 2018, this compound addresses a critical limitation of peptide-based GLP-1 therapies: the requirement for injection. Unlike traditional peptide GLP-1 agonists that undergo rapid degradation in the gastrointestinal tract, orforglipron’s unique small-molecule architecture confers remarkable stability in the gastric environment, enabling effective oral bioavailability of 20-40% without requiring absorption enhancers or strict administration restrictions. With over 3,000 participants enrolled in Phase 3 clinical trials as of 2025, orforglipron has demonstrated efficacy comparable to injectable GLP-1 therapies while offering the convenience of once-daily oral dosing.

Chemical Structure

[IMAGE PLACEHOLDER] Insert 2D chemical structure image here Image URL: https://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi?cid=137319706&t=l Alt text: Orforglipron molecular structure diagram showing nonpeptide small-molecule architecture Source credit: PubChem Position: Center-aligned below heading

2D molecular structure (Source: PubChem)

Technical Specifications

The molecule’s low molecular weight (under 900 Da) distinguishes it from peptide-based GLP-1 agonists, which typically exceed 3,000-4,000 Da. This compact structure enables oral absorption without permeation enhancers while maintaining high-affinity binding to the GLP-1 receptor with an inhibition constant (Ki) of approximately 1 nanomolar.

Orforglipron Mechanism of Action

Orforglipron activates the glucagon-like peptide-1 receptor through a distinct molecular mechanism compared to peptide-based agonists, producing metabolic effects via biased receptor signaling that favors cyclic AMP pathway activation while minimizing beta-arrestin recruitment. This pharmacological profile may reduce receptor desensitization and contribute to sustained therapeutic efficacy with once-daily dosing.

Primary Cellular Pathways

GLP-1 Receptor Binding – Distinct Activation Site

Research has demonstrated that orforglipron binds to the transmembrane domain of the GLP-1 receptor, occupying a pocket within the receptor that overlaps with but differs from the binding site of native GLP-1 peptide¹. Key characteristics include:

• High-affinity binding with Ki approximately 1 nanomolar, comparable to peptide agonists
• Activation of receptor through distinct amino acid interactions within transmembrane helices
• Selective activation with negligible cross-reactivity at GLP-2 or glucagon receptors
• Low receptor occupancy (estimated <10%) sufficient to produce full biological response in vivo

Competition binding studies using radiolabeled orforglipron confirmed selective engagement of GLP-1 receptors without off-target effects at related receptors².

Cyclic AMP Signaling – Biased Agonism

Orforglipron functions as a partial agonist with preferential activation of G protein-coupled signaling pathways over beta-arrestin recruitment³. This biased signaling profile includes:

• Potent stimulation of cyclic AMP production in cells expressing GLP-1 receptors
• Activation of downstream protein kinase A signaling cascades
• Enhanced insulin secretion from pancreatic beta-cells in glucose-dependent manner
• Reduced beta-arrestin pathway activation compared to full agonists

Signal transduction assays revealed that orforglipron exhibits low intrinsic efficacy for beta-arrestin recruitment, potentially reducing receptor internalization and desensitization⁴.

Glucoregulatory Effects – Glucose-Dependent Insulin Secretion

Studies in animal models and human trials demonstrate multiple mechanisms of glycemic control⁵:

• Enhanced insulin secretion from pancreatic beta-cells in response to elevated glucose
• Suppression of inappropriate glucagon release from pancreatic alpha-cells
• Improved insulin sensitivity in peripheral tissues
• Glucose-dependent mechanism reduces hypoglycemia risk compared to insulin

Phase 3 clinical trials showed hemoglobin A1c reductions of 1.3-1.8 percentage points from baseline across dose ranges⁶.

Appetite Regulation – Central Nervous System Effects

Orforglipron engages GLP-1 receptors in appetite-regulating brain regions, contributing to weight loss effects⁷:

• Activation of receptors in hypothalamus and brainstem appetite centers
• Reduced food intake through enhanced satiety signaling
• Delayed gastric emptying, prolonging feelings of fullness
• Modulation of reward pathways involved in food preference

Target engagement studies using genetically modified animal models confirmed orforglipron distribution to brain regions consistent with peptide-based GLP-1 agonists⁸.

Cardiovascular and Metabolic Benefits

Clinical investigations have documented improvements in cardiometabolic parameters beyond glucose and weight⁹:

• Reductions in blood pressure (both systolic and diastolic)
• Favorable lipid profile changes (triglycerides, cholesterol)
• Decreased waist circumference and visceral adiposity
• Improvements in inflammatory markers

[CALLOUT BOX – Highlighted] Key Mechanistic Insight: Orforglipron’s biased signaling profile – favoring cyclic AMP activation over beta-arrestin recruitment – distinguishes it from full GLP-1 agonists and may contribute to reduced receptor desensitization. The remarkably low receptor occupancy required for full biological response (estimated <10%) represents an unusual pharmacological property requiring further mechanistic investigation. [END CALLOUT BOX]

Orforglipron Research Applications & Key Findings

Metabolic Disease Research

Type 2 Diabetes Management

Extensive clinical investigation in Phase 2 and Phase 3 trials has examined orforglipron’s effects on glycemic control in adults with type 2 diabetes¹⁰. The ACHIEVE-1 trial (n=559 participants) demonstrated:

• Hemoglobin A1c reductions of 1.24 to 1.48 percentage points with doses of 3-36 mg daily over 40 weeks
• 65-76% of participants achieving hemoglobin A1c below 7.0% (American Diabetes Association treatment target)
• Rapid onset of glycemic improvement observed as early as 4 weeks after treatment initiation
• Fasting plasma glucose reductions of 30-50 mg/dL across dose ranges

The ACHIEVE-2 trial comparing orforglipron to dapagliflozin (an SGLT-2 inhibitor) showed superior hemoglobin A1c reduction of 1.7% versus 0.8%¹¹.

Obesity and Weight Management

Phase 3 obesity trials have evaluated orforglipron in populations with and without type 2 diabetes¹²,¹³. The ATTAIN-1 trial (n=3,127 adults with obesity) demonstrated:

• Mean weight loss of 7.5%, 8.4%, and 11.2% with 6 mg, 12 mg, and 36 mg doses respectively at 72 weeks
• 59.6% of participants on highest dose achieving at least 10% body weight reduction
• 39.6% achieving at least 15% body weight reduction
• Weight loss trajectory suggesting continued reduction beyond trial duration

The ATTAIN-2 trial in participants with both obesity and type 2 diabetes showed mean weight loss of 10.5% (22.9 lbs) with the 36 mg dose over 72 weeks¹⁴.

Cardiometabolic Parameter Improvements

Research across multiple trials has documented consistent improvements in weight-related comorbidities¹⁵:

• Blood pressure reductions of 3-6 mmHg systolic and 2-4 mmHg diastolic
• Triglyceride decreases of 15-25% from baseline
• Improvements in HDL cholesterol levels
• Waist circumference reductions of 5-8 cm across dose ranges

Pharmacological Comparison Studies

Phase 2 dose-response trials compared orforglipron to the injectable GLP-1 agonist dulaglutide¹⁶. Key findings included:

• Superior hemoglobin A1c reduction with orforglipron 12 mg and higher doses versus dulaglutide 1.5 mg weekly
• Comparable or greater weight loss with orforglipron versus dulaglutide
• Similar gastrointestinal adverse event profiles between oral and injectable formulations
• Once-daily oral dosing without food/water restrictions versus weekly injection

Studies in genetically modified rat models (Glp1r S33W) demonstrated weight loss comparable to subcutaneous semaglutide with oral orforglipron administration¹⁷.

[CALLOUT BOX – Highlighted] Important Context: While orforglipron has demonstrated efficacy in Phase 2 and Phase 3 clinical trials involving thousands of participants, it has not received FDA approval as of late 2025. Regulatory submissions were initiated in late 2025 for obesity indication, with diabetes indication submissions expected in 2026. Long-term safety data beyond 72 weeks remain limited, and cardiovascular outcomes trials have not been completed. [END CALLOUT BOX]

Orforglipron Pharmacokinetics & Metabolism

Absorption & Distribution

Orforglipron exhibits favorable pharmacokinetic properties enabling once-daily oral administration without food restrictions¹⁸,¹⁹. Following oral dosing in human studies:

• Oral bioavailability of approximately 20-40%, exceptional for a nonpeptide GLP-1 receptor agonist
• Time to maximum concentration (Tmax) of 4-8 hours post-dose
• Dose-proportional increases in area under the curve and maximum concentration
• No clinically significant food effect on absorption (can be taken with or without meals)

Distribution characteristics include high plasma protein binding (approximately 99%) with preferential distribution to tissues expressing GLP-1 receptors²⁰. Studies using genetically modified animal models demonstrated tissue concentration patterns consistent with receptor-mediated distribution.

Metabolism & Elimination

Metabolic pathways for orforglipron involve hepatic metabolism, though complete characterization remains ongoing²¹. Available research indicates:

• Half-life of 29-49 hours in human studies, supporting once-daily dosing
• Primary metabolism via cytochrome P450 3A4 (CYP3A4) enzyme system
• Steady-state concentrations achieved after approximately 5-7 days of daily dosing
• Accumulation ratio of approximately 2-3 fold at steady state

The prolonged half-life relative to single-dose kinetics (24-35 hours) suggests possible metabolite formation or tissue redistribution contributing to extended plasma exposure²².

Excretion Pathways

Elimination routes include both hepatic and renal pathways²³:

• Metabolites excreted primarily through hepatic elimination
• Renal clearance contributes to overall drug elimination
• No significant accumulation observed in chronic dosing studies up to 72 weeks
• Dose adjustments not required for mild-to-moderate renal impairment in clinical trials

A notable pharmacological paradox exists: despite achieving peak concentrations within 4-8 hours and maintaining steady-state levels, the glucose-lowering and weight-reducing effects persist throughout the 24-hour dosing interval, suggesting sustained receptor engagement or downstream signaling despite fluctuating plasma concentrations.

Orforglipron Research Protocols & Administration

Dosing in Published Research

Clinical investigations have employed escalating dose strategies to optimize efficacy and tolerability:

• Phase 1 studies (healthy volunteers): 0.3-24 mg daily with weekly escalation
• Phase 2 studies (type 2 diabetes): 9-45 mg daily maintenance doses
• Phase 3 ACHIEVE trials (type 2 diabetes): 3 mg, 12 mg, and 36 mg daily
• Phase 3 ATTAIN trials (obesity): 6 mg, 12 mg, and 36 mg daily
• Dose escalation protocols: Gradual weekly increases over 4-12 weeks to target dose

Important: These are investigational doses used in human clinical trials conducted under medical supervision with defined inclusion/exclusion criteria. Orforglipron dosing protocols cannot be extrapolated to other populations due to significant interindividual variability in pharmacokinetics, receptor expression, comorbidity profiles, and concomitant medication use. Clinical trials employed specific dose escalation schedules to optimize tolerability.

Administration Routes in Research

Orforglipron has been studied exclusively via oral administration:

• Oral capsule formulation – Used in all clinical trials; no injection required
• Once-daily dosing – Administered at any time of day consistently
• No food restrictions – Can be taken with or without meals, unlike peptide-based oral GLP-1 agonists
• No water restrictions – Does not require fasting or limited fluid intake for absorption

The absence of meal-timing restrictions distinguishes orforglipron from oral semaglutide, which requires administration 30 minutes before food with no more than 120 mL water.

Common Study Populations

Orforglipron has been investigated in diverse clinical populations:

• Healthy volunteers – Phase 1 safety and pharmacokinetic characterization (n=92)
• Adults with type 2 diabetes – Phase 2 and 3 efficacy trials; hemoglobin A1c 7.0-10.5%; ages 18-70 years
• Adults with obesity – Phase 2 and 3 weight management trials; BMI ≥30 kg/m² or ≥27 kg/m² with comorbidity
• Adults with obesity and type 2 diabetes – Combined population trials (ATTAIN-2: n=2,500+)
• Cell culture systems – HEK293 cells expressing human GLP-1 receptors for mechanistic studies
• Genetically modified rodent models – Rats with humanized GLP-1 receptors (Glp1r S33W) for preclinical research

Research Limitations & Regulatory Status

Critical Gaps in Current Evidence

Despite successful completion of multiple Phase 3 clinical trials, orforglipron faces important translational considerations that warrant careful evaluation.

Incomplete Long-Term Safety Data

The duration of completed trials limits understanding of chronic safety:

• Maximum trial duration of 72 weeks in Phase 3 studies; effects beyond this timeframe unknown
• Long-term cardiovascular outcomes not yet evaluated in dedicated trials
• Effects on cancer risk or tumor progression not assessed over years of continuous use
• Durability of weight loss and glycemic control beyond 1-2 years unstudied

Mechanistic Understanding Gaps

Fundamental aspects of orforglipron pharmacology require additional investigation:

• Biased agonism mechanisms not fully characterized at molecular level
• Relationship between receptor occupancy and biological response incompletely understood
• Active metabolite contributions to efficacy versus parent compound unclear
• Tissue-specific receptor engagement patterns require further definition

Gastrointestinal Tolerability Concerns

Clinical trials documented dose-dependent discontinuation rates:

• Treatment discontinuation due to adverse events ranging from 5-10% across doses
• Gastrointestinal events (nausea, diarrhea, constipation, vomiting) most common side effects
• Discontinuation rates higher than placebo but comparable to injectable GLP-1 agonists
• Long-term adherence rates in real-world practice settings remain unknown

Comparative Effectiveness Questions

Direct head-to-head comparisons with established therapies are limited:

• No published trials directly comparing orforglipron to injectable semaglutide or tirzepatide
• Indirect comparisons suggest modestly lower weight loss than highest-dose injectable GLP-1 agonists
• Cost-effectiveness analyses not yet available
• Patient preference data for oral versus injectable formulations limited

Regulatory & Clinical Development Status

FDA Position

Orforglipron has not received FDA approval for any indication as of late 2025:

• Regulatory submission for obesity indication initiated by Eli Lilly in late 2025
• Type 2 diabetes indication submission anticipated in 2026
• FDA priority review voucher granted, potentially expediting review timeline to 1-2 months
• Not legally available for prescription, compounding, or over-the-counter purchase
• Investigational status – available only through approved clinical trials

The FDA has established the Commissioner’s National Priority Review Voucher program, and orforglipron may be among the first drugs reviewed under this expedited pathway designed for high-burden chronic conditions.

International Regulatory Status

Orforglipron regulatory pathways vary by jurisdiction:

• European Medicines Agency: Submission timeline not publicly disclosed as of late 2025
• UK NICE: Separate evaluation required for National Health Service formulary inclusion
• Global submissions: Eli Lilly announced intent for worldwide regulatory filings
• No approvals granted by any health authority worldwide as of late 2025

WADA Prohibition Status

The World Anti-Doping Agency classification for orforglipron has not been explicitly published, but considerations include:

• GLP-1 receptor agonists generally not listed as prohibited substances by WADA as of 2025
• Metabolic modulators evaluated on case-by-case basis for performance enhancement potential
• Orforglipron’s investigational status precludes definitive WADA classification
• Athletes should consult with sports medicine physicians regarding emerging regulations

Research Classification: Orforglipron is available only for clinical research through approved investigational protocols. It is not approved for medical use, veterinary applications, or dietary supplement inclusion. All research must be conducted under appropriate institutional review board oversight with informed consent procedures conforming to Good Clinical Practice guidelines and the Declaration of Helsinki.

Lead Researcher Spotlight

Dr. Kyle W. Sloop, PhD

Principal Research Scientist

Diabetes, Obesity and Complications Therapeutic Area

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA

Dr. Kyle W. Sloop has served as the lead scientific investigator for orforglipron’s pharmacological characterization and clinical development at Eli Lilly and Company. His research team has published seminal work defining the molecular mechanisms underlying nonpeptide GLP-1 receptor agonism and establishing the pharmacological foundation for this novel therapeutic class.

Dr. Sloop’s research contributions include:

• Characterization of orforglipron’s binding properties and high-affinity interaction with GLP-1 receptors (Ki approximately 1 nanomolar)
• Elucidation of biased agonism mechanisms favoring cyclic AMP signaling over beta-arrestin recruitment
• Development of genetically modified animal models to enable preclinical efficacy testing
• Demonstration that low receptor occupancy produces full biological responses with orforglipron
• Leadership of cross-functional teams integrating medicinal chemistry, pharmacology, and clinical development

His work has established the pharmacological basis for targeting peptide receptors with nonpeptide small molecules, potentially informing drug discovery strategies beyond GLP-1 receptor agonists. Dr. Sloop has authored multiple peer-reviewed publications in high-impact journals including Science Translational Medicine and Proceedings of the National Academy of Sciences documenting orforglipron’s pharmacological properties.

Disclaimer: This spotlight is provided for educational purposes to acknowledge scientific contributions to orforglipron research. Cenexa Labs has no affiliation with Dr. Sloop or Eli Lilly and Company, and this information does not constitute an endorsement of any products or services.

References

1. Sloop, K.W., Cox, A.L., Wainscott, D.B., White, A., Droz, B.A., Stutsman, C., Showalter, A.D., Suter, T.M., Dunbar, J.D., Snider, B.M., O’Farrell, L.S., Hewitt, N., Ruble, J.C., Padgett, L.R., Woerly, E.M., Peterson, J.A., Coskun, T., Liu, Z., Coutant, D.E., Ai, M., Emmerson, P.J., Sangwung, P., & Willard, F.S. (2024). The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron. Science Translational Medicine, 16(778), eadp5765. PubMed
   
2. Sloop, K.W., Cox, A.L., Wainscott, D.B., White, A., Droz, B.A., Stutsman, C., Showalter, A.D., Suter, T.M., Dunbar, J.D., Snider, B.M., O’Farrell, L.S., Hewitt, N., Ruble, J.C., Padgett, L.R., Woerly, E.M., Peterson, J.A., Coskun, T., Liu, Z., Coutant, D.E., Ai, M., Emmerson, P.J., Sangwung, P., & Willard, F.S. (2024). The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron. Science Translational Medicine, 16(778), eadp5765. PubMed
   
3. Wharton, S., Blevins, T., Connery, L., Rosenstock, J., Raha, S., Liu, R., Ma, X., Mather, K.J., Haupt, A., Robins, D., Pratt, E., Kazda, C., König, M., & GZGI Investigators. (2023). Daily oral GLP-1 receptor agonist orforglipron for adults with obesity. New England Journal of Medicine, 389(10), 877-888. PubMed
   
4. Sloop, K.W., Cox, A.L., Wainscott, D.B., White, A., Droz, B.A., Stutsman, C., Showalter, A.D., Suter, T.M., Dunbar, J.D., Snider, B.M., O’Farrell, L.S., Hewitt, N., Ruble, J.C., Padgett, L.R., Woerly, E.M., Peterson, J.A., Coskun, T., Liu, Z., Coutant, D.E., Ai, M., Emmerson, P.J., Sangwung, P., & Willard, F.S. (2024). The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron. Science Translational Medicine, 16(778), eadp5765. PubMed
   
5. Rosenstock, J., Hsia, S., Nevarez Ruiz, L., Eyde, S., Cox, D., Wu, W.S., Liu, R., Li, J., Fernández Landó, L., Denning, M., Ludwig, L., Chen, Y., & ACHIEVE-1 Trial Investigators. (2025). Orforglipron, an oral small-molecule GLP-1 receptor agonist, in early type 2 diabetes. New England Journal of Medicine, 393(11), 1065-1076. PubMed
   
6. Rosenstock, J., Hsia, S., Nevarez Ruiz, L., Eyde, S., Cox, D., Wu, W.S., Liu, R., Li, J., Fernández Landó, L., Denning, M., Ludwig, L., Chen, Y., & ACHIEVE-1 Trial Investigators. (2025). Orforglipron, an oral small-molecule GLP-1 receptor agonist, in early type 2 diabetes. New England Journal of Medicine, 393(11), 1065-1076. PubMed
   
7. Sloop, K.W., Cox, A.L., Wainscott, D.B., White, A., Droz, B.A., Stutsman, C., Showalter, A.D., Suter, T.M., Dunbar, J.D., Snider, B.M., O’Farrell, L.S., Hewitt, N., Ruble, J.C., Padgett, L.R., Woerly, E.M., Peterson, J.A., Coskun, T., Liu, Z., Coutant, D.E., Ai, M., Emmerson, P.J., Sangwung, P., & Willard, F.S. (2024). The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron. Science Translational Medicine, 16(778), eadp5765. PubMed
   
8. Sloop, K.W., Cox, A.L., Wainscott, D.B., White, A., Droz, B.A., Stutsman, C., Showalter, A.D., Suter, T.M., Dunbar, J.D., Snider, B.M., O’Farrell, L.S., Hewitt, N., Ruble, J.C., Padgett, L.R., Woerly, E.M., Peterson, J.A., Coskun, T., Liu, Z., Coutant, D.E., Ai, M., Emmerson, P.J., Sangwung, P., & Willard, F.S. (2024). The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron. Science Translational Medicine, 16(778), eadp5765. PubMed
   
9. Wharton, S., Aronne, L.J., Stefanski, A., Alfaris, N.F., Ciudin, A., Yokote, K., Halpern, B., & ATTAIN-1 Trial Investigators. (2025). Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment. New England Journal of Medicine, NEJMoa2511774. PubMed
   
10. Rosenstock, J., Hsia, S., Nevarez Ruiz, L., Eyde, S., Cox, D., Wu, W.S., Liu, R., Li, J., Fernández Landó, L., Denning, M., Ludwig, L., Chen, Y., & ACHIEVE-1 Trial Investigators. (2025). Orforglipron, an oral small-molecule GLP-1 receptor agonist, in early type 2 diabetes. New England Journal of Medicine, 393(11), 1065-1076. PubMed
    
11. Eli Lilly and Company. (2025). Lilly’s oral GLP-1, orforglipron, demonstrated statistically significant efficacy results and a safety profile consistent with injectable GLP-1 medicines in successful Phase 3 trial. (Company announcement; peer-reviewed publication pending)
12. Wharton, S., Aronne, L.J., Stefanski, A., Alfaris, N.F., Ciudin, A., Yokote, K., Halpern, B., & ATTAIN-1 Trial Investigators. (2025). Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment. New England Journal of Medicine, NEJMoa2511774. PubMed
    
13. Wharton, S., Blevins, T., Connery, L., Rosenstock, J., Raha, S., Liu, R., Ma, X., Mather, K.J., Haupt, A., Robins, D., Pratt, E., Kazda, C., König, M., & GZGI Investigators. (2023). Daily oral GLP-1 receptor agonist orforglipron for adults with obesity. New England Journal of Medicine, 389(10), 877-888. PubMed
    
14. Horn, D.B., Ryan, D.H., Giljanovic Kis, S., et al. (2025). Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. The Lancet, S0140-6736(25)02165-8.
15. Wharton, S., Aronne, L.J., Stefanski, A., Alfaris, N.F., Ciudin, A., Yokote, K., Halpern, B., & ATTAIN-1 Trial Investigators. (2025). Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment. New England Journal of Medicine, NEJMoa2511774. PubMed
    
16. Frias, J.P., Hsia, S., Eyde, S., Liu, R., Ma, X., König, M., Kazda, C., Mather, K.J., Haupt, A., & Pratt, E. (2023). Efficacy and safety of oral orforglipron in patients with type 2 diabetes: A multicentre, randomised, dose-response, phase 2 study. The Lancet, 402(10400), 472-483.
17. Sloop, K.W., Cox, A.L., Wainscott, D.B., White, A., Droz, B.A., Stutsman, C., Showalter, A.D., Suter, T.M., Dunbar, J.D., Snider, B.M., O’Farrell, L.S., Hewitt, N., Ruble, J.C., Padgett, L.R., Woerly, E.M., Peterson, J.A., Coskun, T., Liu, Z., Coutant, D.E., Ai, M., Emmerson, P.J., Sangwung, P., & Willard, F.S. (2024). The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron. Science Translational Medicine, 16(778), eadp5765. PubMed
    
18. Pratt, E., Ma, X., Liu, R., Robins, D., Coskun, T., Haupt, A., Sloop, K.W., & Benson, C. (2023). 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 participants. Diabetes, Obesity and Metabolism, 25(11), 3226-3236. PubMed
    
19. Coskun, T., Urva, S., Roell, W.C., Qu, H., Loghin, C., Moyers, J.S., O’Farrell, L.S., Briere, D.A., Sloop, K.W., Thomas, M.K., Haupt, A., & Benson, C. (2024). 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 Therapy, 15(3), 735-751.
20. Sloop, K.W., Cox, A.L., Wainscott, D.B., White, A., Droz, B.A., Stutsman, C., Showalter, A.D., Suter, T.M., Dunbar, J.D., Snider, B.M., O’Farrell, L.S., Hewitt, N., Ruble, J.C., Padgett, L.R., Woerly, E.M., Peterson, J.A., Coskun, T., Liu, Z., Coutant, D.E., Ai, M., Emmerson, P.J., Sangwung, P., & Willard, F.S. (2024). The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron. Science Translational Medicine, 16(778), eadp5765. PubMed
    
21. Pratt, E., Ma, X., Liu, R., Robins, D., Coskun, T., Sloop, K.W., Haupt, A., & Benson, C. (2023). 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 type 2 diabetes. Diabetes, Obesity and Metabolism, 25(8), 2313-2324.
22. Pratt, E., Ma, X., Liu, R., Robins, D., Coskun, T., Haupt, A., Sloop, K.W., & Benson, C. (2023). 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 participants. Diabetes, Obesity and Metabolism, 25(11), 3226-3236. PubMed
    
23. Coskun, T., Urva, S., Roell, W.C., Qu, H., Loghin, C., Moyers, J.S., O’Farrell, L.S., Briere, D.A., Sloop, K.W., Thomas, M.K., Haupt, A., & Benson, C. (2024). 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 Therapy, 15(3), 735-751.

All references open in new window. These citations are provided for educational and research purposes only. This information is not intended to diagnose, treat, cure, or prevent any disease. Orforglipron is intended for clinical research use only and has not been approved by regulatory authorities for medical use.