orforglipron (OWL833) / Roche, Eli Lilly - LARVOL DELTA

Orforglipron, an Oral GLP-1 Receptor Agonist, in Early Type 2 Diabetes. (PubMed, N Engl J Med) - No abstract available

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Orforglipron, an Oral GLP-1 Receptor Agonist, in Early Type 2 Diabetes. (PubMed, N Engl J Med) - No abstract available

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Orforglipron, an Oral GLP-1 Receptor Agonist, in Early Type 2 Diabetes. Reply. (PubMed, N Engl J Med) - No abstract available

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Orforglipron, an Oral GLP-1 Receptor Agonist, in Early Type 2 Diabetes. (PubMed, N Engl J Med) - No abstract available

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Harnessing GLP-1 Receptor Agonists for Obesity Treatment: Prospects and Obstacles on the Horizon. (PubMed, J Obes) - "Currently, liraglutide, semaglutide, and tirzepatide are FDA-approved for obesity treatment, while other agents are used off-label...Novel agents including CagriSema and higher dose oral semaglutide are advancing through clinical trials, while pivotal trial results for orforglipron, mazdutide, retatrutide, and survodutide are anticipated to further expand the therapeutic landscape...The convergence of pharmacological innovation, digital health strategies, and equitable care initiatives is expected to revolutionize obesity therapeutics in the coming decade. Priorities for future research include sustaining long-term weight loss, establishing disease-modifying potential in nonmetabolic disorders, and addressing health equity concerns to ensure broader global benefit."

Journal • Review • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Congestive Heart Failure • Diabetes • Dyslipidemia • Genetic Disorders • Heart Failure • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Nephrology • Obesity • Renal Disease • Type 2 Diabetes Mellitus

Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review. (PubMed, Medicina (Kaunas)) - "Orlistat commonly linked to steatorrhea and flatulence, while phentermine was associated with reduced GI motility. Newer agents, including retatrutide and orforglipron, also demonstrated notable GI side effect profiles...Tailored titration schedules, proactive patient counseling, and standardized adverse event reporting may improve tolerability. Further research is warranted to evaluate long-term GI outcomes and compare safety across emerging pharmacologic agents."

Adverse events • Journal • Review • Constipation • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Metabolic Disorders • Obesity

ATTAIN-PAD: Efficacy and Safety of Orforglipron in Participants With Peripheral Artery Disease (clinicaltrials.gov) - P3 | N=1205 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Peripheral Arterial Disease

A Study of Orforglipron (LY3502970) on Cardiovascular Outcomes in Adults With Atherosclerotic Cardiovascular Disease and/or Chronic Kidney Disease (ATTAIN-Outcomes) (clinicaltrials.gov) - P3 | N=7140 | Not yet recruiting | Sponsor: Eli Lilly and Company

Adverse events • New P3 trial • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease

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. (PubMed, Lancet) - P3 | "In adults with obesity or overweight and type 2 diabetes, statistically superior reduction in bodyweight compared with placebo was demonstrated by once-daily orforglipron as an adjunct to lifestyle modification, with a safety profile similar to other GLP-1 receptor agonists."

Journal • P3 data • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Engineered nutrient-stimulated hormonal multi-agonist for precision targeting of obesity and metabolic disorders. (PubMed, Clin Mol Hepatol) - "Tirzepatide (GLP-1/GIP dual agonist), CagriSema (GLP-1/amylin dual agonist), and retatrutide (GLP-1/GIP/glucagon triple agonist) have achieved unprecedented levels of weight loss and glycemic improvement, with certain agents also demonstrating hepatic, cardiovascular, and inflammatory benefits. Non-peptidyl oral GLP-1RAs, such as orforglipron, offer novel formulation strategies to enhance treatment accessibility and adherence...These therapies are poised to emerge as key components of precision metabolic medicine. This review article explores the mechanistic basis, pharmacological characteristics, and clinical data supporting the use of engineered NUSH-based peptide therapies for obesity and its related metabolic disorders, with particular emphasis on recent progress in the development and clinical application of dual and triple agonists."

Journal • Cardiovascular • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

Orforglipron in type 2 diabetes mellitus and obesity: an overview. (PubMed, Expert Rev Clin Pharmacol) - "Orforglipron is a promising treatment option for T2DM and overweight or obesity, in terms of glucose control and weight loss. The increased frequency of adverse events, particularly in those receiving high doses and after rapid dose escalation, requires caution before widespread use."

Journal • Review • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

A phase 1 single and multiple ascending dose study of orforglipron in Japanese participants with type 2 diabetes. (PubMed, J Diabetes Investig) - "In Japanese participants, safety, pharmacokinetic, and pharmacodynamic results were similar to those of previous orforglipron studies. The safety and tolerability of orforglipron were also consistent with those of other glucagon-like peptide-1 receptor agonists. Orforglipron is a potential new treatment option for Japanese patients with type 2 diabetes."

Journal • P1 data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy and Safety of Orforglipron in Obese Adults With or Without Diabetes: A Systematic Review and Meta-Analysis. (PubMed, Endocrinol Diabetes Metab) - "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."

Clinical • Journal • Retrospective data • Review • Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Preclinical Characterization of AM-710, a Novel Ultra-Long-Acting Small-Molecule GLP-1R Agonist (OBESITY WEEK 2025) - "These data support the ultra-long-acting profile of AM-710, a novel prodrug of the small molecule GLP1R agonist orforglipron with the potential to provide infrequent dosing with improved peak-to-trough PK. Based on its favorable in vivo PK/PD profile, further investigation of AM-710 is warranted, including progression to IND-enabling studies."

Preclinical • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Discovery and Nonclinical Profile of AMB-234, a Novel, Orally Bioavailable GLP-1 Receptor Agonist (OBESITY WEEK 2025) - "Where appropriate, benchmark compounds (orforglipron and aleniglipron) were included. The novel, orally available small molecule GLP-1 agonist, AMB-234, demonstrated subnanomolar potency with desirable ADME, pharmacokinetic properties and robust pharmacodynamic activity in transgenic humanized GLP-1R mice. These data showcase the potential of AMB-234 as a treatment for obesity, type 2 diabetes and other cardiometabolic disorders. Nonclinical studies to characterize AMB-234 in obesity models in mice are in progress."

Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Orally Available GLP-1RA Improve Glucose Homeostasis and Reduce Bodyweight in hGLP-1R Knock-In Mice (OBESITY WEEK 2025) - "DIO-hGLP-1 KI mice were treated with vehicle control, CKD compounds, 10 mg/kg orforglipron or 30 nmol/kg semaglutide... These results highlight the potential of our compounds to improve glucose homeostasis and promote weight loss, offering a novel therapeutic option for the treatment of metabolic diseases."

Preclinical • Chronic Kidney Disease • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • ARRB1

Characterization of a New Humanized GLP-1R Mouse Model for Small-Molecule GLP-1R agonists Evaluation (OBESITY WEEK 2025) - "Pharmacological characterization involved acute (n=7-11/group) and chronic (n=10/group) treatment studies to assess the metabolic effects of semaglutide (a peptide GLP1RA, 10 and 30 nmol/kg) and orforglipron (a small-molecule GLP1RA, 0.3 and 3 mg/kg) in lean and diet-induced obese (DIO) hGLP1R and wild-type (WT) mice... These findings establish the Gubra hGLP1R mouse as a translational model for evaluating metabolic effects of small-molecule GLP1RAs for the treatment of obesity and related disorders."

Preclinical • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • FOS

Novel THR-β Agonist CG-0416 Potentiates GLP-1R Based Treatments With Improved Muscle Preservation (OBESITY WEEK 2025) - "Background: Thyroid hormone receptor beta (THR-β) biased agonists, such as Resmetirom and VK2809, are clinically validated for treating metabolic-associated steatohepatitis (MASH)...Given its complementary mechanism to GLP-1 receptor agonists, we evaluated the combination of CG-0416 with either semaglutide or orforglipron in a diet-induced obesity (DIO) mouse model to assess weight loss quantity and quality...Mice received daily treatments for 4 weeks of either vehicle, CG-0416 (1, 3.3, and 10 mg/kg, oral), or semaglutide (10 nmol/kg, subcutaneous) assessed as monotherapy and in combinations... CG-0416 shows significantly better in vitro activity and liver enrichment compared with VK-2809 (reported previously). Unlike most other THR-β agonists, CG-0416 does induce weight loss on its own through its highly efficient stimulation of fat metabolism in the liver. At highest 10 mg/kg dose, weight loss is similar to that of 10 nmol/kg semaglutide."

Fibrosis • Genetic Disorders • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

The Evolution of Oral Incretin-based Therapies for Obesity (OBESITY WEEK 2025) - "The prevalence of obesity across the world continues to rise, and this is now recognised as one of the most important public health problems, which needs to be addressed.The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from the gut after nutrient intake and play an important role in glucose homoeostasis and in the control of food intake, nutrient assimilation, and whole-body metabolism.Recently developed GLP-1-based therapies for weight management represent highly effective treatment options for people living with obesity.The field of GLP-1-based medicines has evolved from selective GLP-1 RAs, liraglutide and semaglutide, which were the first incretin-based therapies approved for weight management. The more recently approved tirzepatide, which activates both GLP-1 and GIP receptors has demonstrated higher efficacy in terms of body weight reduction, while retatrutide, a triple receptor agonist..."

Genetic Disorders • Obesity

ATTAIN-2: Background, Rationale, and Study Design (OBESITY WEEK 2025) - P3 | "A phase 3, randomized, double-blind, 72-week study ATTAIN-2 (ClinicalTrials.gov, NCT05872620) assessed the efficacy and safety of orforglipron, a once-daily, oral, non-peptide glucagon-like peptide-1 receptor agonist (GLP-1 RA), compared with placebo, in adult participants with obesity or overweight and T2D... N/A"

Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Severe Hypoglycemia • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Commentary (OBESITY WEEK 2025) - "In ATTAIN-2, the non-peptide glucagon-like peptide-1 receptor agonist (GLP-1 RA), orforglipron, has been evaluated as a potentially effective once-daily oral treatment for weight reduction in adults with obesity or overweight and type 2 diabetes (T2D). The commentary will focus on clinically meaningful outcomes in body weight reductions and significant improvements in glycemic control, blood pressure, and lipid parameters. This section will also discuss the overall safety profile of orforglipron in comparison to the known profile of incretin-based therapies."

Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

ATTAIN-2: Safety Results (OBESITY WEEK 2025) - "Background: N/A N/A During this presentation the safety findings for orforglipron (6 mg, 12 mg, or 36 mg) in participants with obesity or overweight and type 2 diabetes in ATTAIN-2 study will be reviewed... N/A"

Clinical • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

ATTAIN-1: Study Design and Results (OBESITY WEEK 2025) - P3 | "Background: The presentation aims to provide an overview of ATTAIN-1, a phase 3 clinical trial investigating orforglipron, a once-daily oral non-peptide GLP-1 receptor agonist in people with obesity or overweight... N/A"

Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Eli Lilly…expects the U.S. Food and Drug Administration to approve its experimental oral obesity drug, orforglipron, by March 2026, its chief executive said on Thursday (Reuters)

FDA approval • Obesity

Lilly and U.S. government agree to expand access to obesity medicines to millions of Americans (PRNewswire) - "Starting as early as April 1, 2026, Medicare beneficiaries will pay no more than $50 per month for Zepbound (tirzepatide), available in a multi-dose pen, and for orforglipron, Lilly's convenient once-daily obesity pill, provided both receive approval from the U.S. Food and Drug Administration (FDA). States will also have the ability to expand access to Zepbound and orforglipron through Medicaid....Zepbound multi-dose pen will be available at the lowest dose at $299, with additional doses up to $449 representing a $50 discount to current direct-to-patient prices....Orforglipron will be available with the lowest dose starting at $149 with additional doses up to $399."

Commercial • Obesity