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

Lilly, chasing Novo, expects second-quarter FDA decision on obesity pill (Yahoo Finance) - "A second-quarter launch would be well-timed for Lilly to begin selling orforglipron to the millions of people enrolled in Medicare, which will have broad access to obesity medications beginning in April."

FDA approval • Launch US • Obesity

Generation and characterisation of a humanised GLP-1 receptor mouse model for translational drug development. (PubMed, EBioMedicine) - "These findings establish the hGLP1R mouse as a robust and translational platform for advancing the discovery and evaluation of novel small-molecule GLP1RAs targeting obesity and related metabolic diseases."

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

Eli Lilly (LLY) Prepares for Global Launch of Weight Loss Pill (Gurufocus) - "Eli Lilly (LLY) is gearing up for the anticipated approval of its new weight loss medication, orforglipron, expected this quarter. The FDA granted a priority voucher to the drug, reducing its review period to just one to two months. The company has invested substantial funds in manufacturing facilities to meet global demand. Orforglipron's starting dose is priced at $149 monthly, with higher doses costing up to $399."

Commercial • FDA approval • Obesity

EFFECT OF ORFORGLIPRON, A NOVEL ORAL GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONIST, ON LIPID PANEL AND BLOOD PRESSURE: META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS (ACC 2026) - "Abstract is embargoed at this time."

Retrospective data

Efficacy and safety of orforglipron in type 2 diabetes mellitus and obesity: a GRADE-assessed meta-analysis and trial sequential analysis with subgroup evaluations by diabetic status, obesity status, and dose regimens. (PubMed, Acta Diabetol) - No abstract available

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

Rewriting Diabetes Therapy: How Incretin Modulation is Transforming Cardiovascular and Renal Outcomes. (PubMed, Diabetes Ther) - "Incretin-based therapy has shifted care from glucose-centric targets to cardiorenal risk reduction. GLP-1RA are guideline-endorsed for patients with T2DM and high CV/renal risk irrespective of HbA1c; dual agonists and oral small-molecule agents may broaden indications pending definitive outcome evidence."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Genetic Disorders • Heart Failure • Metabolic Disorders • Nephrology • Obesity • Renal Disease • Type 2 Diabetes Mellitus

Gastrointestinal side effects of the non-peptide GLP-1 receptor agonists: A systematic review and meta-analysis. (PubMed, Medicine (Baltimore)) - "Gastrointestinal side effects of the non-peptide GLP-1 receptor agonists were widely reported but less frequent compared to placebo/ standard treatment. There was no significant dose-dependent increase in the side effects of these medications."

Adverse events • Clinical • Journal • Retrospective data • Review • Constipation • Diabetes • Dyspepsia • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Metabolic Disorders • Type 2 Diabetes Mellitus

The efficacy and safety of danuglipron and orforglipron in patients with type 2 diabetes and obesity: a systematic review and meta-analysis. (PubMed, Front Endocrinol (Lausanne)) - "The oral GLP-1 RAs danuglipron and orforglipron are capable of improving blood glucose levels and reducing weight; however, they also pose an increased risk of gastrointestinal AEs. Further longitudinal studies are warranted to gain a deeper understanding of their efficacy, safety and tolerability."

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

A Study of Orforglipron for the Maintenance of Body Weight Reduction in Participants Who Have Obesity or Overweight With Weight-Related Comorbidities (ATTAIN-MAINTAIN) (clinicaltrials.gov) - P3 | N=376 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Obesity

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

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

Eli Lilly and Company…announced positive topline results from the ATTAIN-MAINTAIN trial (PRNewswire) - "The Phase 3 study evaluated orforglipron, an investigational, once-daily oral small molecule glucagon-like peptide-1 (GLP-1) receptor agonist, for weight maintenance over 52 weeks after initial treatment for 72 weeks with the highest tolerated doses of Wegovy (semaglutide) or Zepbound (tirzepatide), in participants from SURMOUNT-5 who were offered the opportunity to be re-randomized to receive orforglipron or placebo. At one year, orforglipron met the primary and all key secondary endpoints compared to placebo, delivering superior weight maintenance as an adjunct to a healthy diet and physical activity, using the efficacy estimand and modified treatment-regimen estimand."

P3 data: top line • Obesity

Lilly has submitted orforglipron to the U.S. Food and Drug Administration for the treatment of obesity (PRNewswire) - "Detailed results from the ATTAIN-MAINTAIN trial will be presented at a future medical meeting and published in a peer-reviewed journal next year."

FDA filing • P3 data • Obesity

Orforglipron: A Novel Oral GLP-1 Agonist for the Treatment of Obesity and Diabetes. (PubMed, Cardiol Rev) - "Given the limitations of injectable GLP-1 RAs and the administration constraints of oral semaglutide, orforglipron offers a major convenience advantage: it is a small molecule with ~79% oral bioavailability that requires no food or water restrictions. A nondose-dependent heart rate increase and a small signal for mild pancreatitis were observed. A class-specific concern exists regarding increased ventricular arrhythmia risk in patients with heart failure with reduced ejection fraction treated with conventional GLP-1 RAs."

Journal • Cardiovascular • Congestive Heart Failure • Diabetes • Genetic Disorders • Heart Failure • Metabolic Disorders • Obesity • Pancreatitis • Type 2 Diabetes Mellitus

Medical Management of Obesity: A Comprehensive Review of Food and Drug Administration (FDA)-Approved and Investigational Therapies. (PubMed, Cureus) - "Approved long-term agents, orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide, semaglutide, and tirzepatide, differ in mechanism, weight-loss magnitude, and safety considerations. Semaglutide and tirzepatide have redefined expectations for pharmacological weight loss, while next-generation drugs, such as oral glucagon-like peptide 1 receptor agonists (e.g., orforglipron) and multireceptor agonists (e.g., retatrutide), show even greater efficacy in early studies...Future research should prioritize direct comparative trials, real-world effectiveness, long-term safety, and strategies to improve access and adherence. This review offers clinicians a concise, evidence-based guide for obesity pharmacotherapy and outlines key research priorities as the treatment landscape rapidly evolves."

FDA event • Journal • Review • Cardiovascular • Genetic Disorders • Obesity • Oncology • Pancreatic Cancer • Pancreatitis • Thyroid Gland Carcinoma

The Obesity Drug Revolution: New Frontiers in Pharmacotherapy. (PubMed, Cureus) - "The current FDA-approved pharmacotherapy consists of orlistat, setmelanotide, phentermine-topiramate, naltrexone-bupropion, liraglutide, semaglutide, and tirzepatide...Orforglipron, a non-peptide oral glucagon-like peptide-1 receptor agonist, offers parenteral efficacy with convenient dosing...Innovative therapeutic approaches, multidisciplinary care, and a patient-centered plan are required for better clinical outcomes. This review highlights the current and emerging therapies designed to enhance long-term outcomes in obesity care."

Journal • Review • Cardiovascular • Diabetes • Dyslipidemia • Genetic Disorders • Hypertension • Inflammation • Metabolic Disorders • Obesity • Psychiatry • Transplantation

Orforglipron: An Investigational Oral Non-Peptide Glucagon-Like Peptide-1 Receptor Agonist as a Treatment Option for Obesity and Type 2 Diabetes (ASHP 2025) - No abstract available

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

One small molecule for man, one giant leap for mankind with obesity. (PubMed, Med) - "Orforglipron, the first oral small-molecule GLP-1 receptor agonist to complete a phase 3 clinical trial, delivers meaningful reductions in body weight and improvements in metabolic health. This advancement moves beyond peptide-based injectables, paving the way for potent obesity therapies that are simpler, more affordable, and accessible to millions worldwide."

Journal • Genetic Disorders • Obesity

Lilly to build $6 billion facility to manufacture active pharmaceutical ingredients in Alabama (PRNewswire) - "This next-generation synthetic medicine active pharmaceutical ingredient (API) facility, the third of four new U.S. sites Lilly plans to announce, will produce small molecule synthetic and peptide medicines....Construction, expected to begin in 2026, is anticipated to generate 3,000 construction jobs as the state-of-the-art facility is built. Completion is expected in 2032....Huntsville site will focus on domestic production of small molecule synthetic and peptide medicines, including Lilly's oral GLP-1, orforglipron."

Commercial • Obesity

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

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