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

A Master Protocol Study of Orforglipron (LY3502970) in Participants With Hypertension and Obesity or Overweight (ATTAIN-Hypertension) GZL2 (clinicaltrials.gov) - P3 | N=487 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P3 trial • Cardiovascular • Genetic Disorders • Hypertension • Obesity

Orforglipron: Primary completion and completion of P1 trial (NCT06824051) for obesity in Dec 2025 (Eli Lilly) - Q1 2025 Results

Trial completion date • Trial primary completion date • Obesity

A Master Protocol Study of Orforglipron (LY3502970) in Participants With Hypertension and Obesity or Overweight (ATTAIN-Hypertension) GZL1 (clinicaltrials.gov) - P3 | N=487 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P3 trial • Cardiovascular • Genetic Disorders • Hypertension • Obesity

A Master Protocol for Orforglipron (LY3502970) in Participants With Hypertension and Obesity or Overweight: (ATTAIN-Hypertension Screening) (clinicaltrials.gov) - P3 | N=974 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P3 trial • Cardiovascular • Genetic Disorders • Hypertension • Obesity

A Study of Orforglipron (LY3502970) in Adult Participants With Obesity or Overweight (clinicaltrials.gov) - P1 | N=120 | Active, not recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity

NVO Stock Dips as Eli Lilly's Oral Weight Loss Drug Shows Promising Results (Gurufocus) - "Novo Nordisk...saw its stock take a significant hit, plunging nearly 8%. This decline followed the announcement from competitor Eli Lilly about its promising Phase 3 trials for a new oral weight loss medication, orforglipron."

Commercial • Obesity

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=300 | Active, not recruiting | Sponsor: Eli Lilly and Company | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

ACHIEVE-1: A Study of Orforglipron (LY3502970) in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone (clinicaltrials.gov) - P3 | N=520 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

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 (PRNewswire) - P3 | N=520 | ACHIEVE-1 (NCT05971940) | Sponsor: Eli Lilly and Company | "Eli Lilly and Company...announced positive topline Phase 3 results from ACHIEVE-1...orforglipron met the primary endpoint of superior A1C reduction compared to placebo at 40 weeks, lowering A1C by an average of 1.3% to 1.6% from a baseline of 8.0%, using the efficacy estimand. In a key secondary endpoint, more than 65% of participants taking the highest dose of orforglipron achieved an A1C less than or equal to 6.5%...The overall safety profile of orforglipron in ACHIEVE-1 was consistent with the established GLP-1 class...The ACHIEVE-1 results will be presented at ADA's 85th...More results from the ACHIEVE Phase 3 clinical trial program will be shared later this year....Lilly expects to submit orforglipron for weight management to global regulatory agencies by the end of this year, with the submission for the treatment of type 2 diabetes anticipated in 2026."

FDA filing • P3 data: top line • Type 2 Diabetes Mellitus

Current Insights, Advantages and Challenges of Small Molecule Glucagon-like Peptide 1 Receptor Agonists: A Scoping Review. (PubMed, J Brown Hosp Med) - "These small molecules offer enhanced tissue permeability, extended half-lives, and the potential for fixed-dose combinations, addressing limitations of injectable formulations. This review explores the preclinical and clinical progress of small-molecule GLP-1RAs, highlighting their potential to redefine diabetes care by improving convenience, adherence, and accessibility for patients."

Journal • Review • Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

First Report of a Phase 3 RCT of Orforglipron, a Small Nonpeptide GLP-1RA, as Monotherapy in Drug-Naïve Type 2 Diabetes with Inadequate Glycemic Control—The ACHIEVE-1 Trial (ADA 2025) - No abstract available

Monotherapy • P3 data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Incretin-based therapies for the treatment of obesity-related diseases (ATTD 2025) - "Liraglutide, semaglutide and tirzepatide are incretin-based therapies currently approved by FDA for the management of obesity, while triple GIPR/GCGR/GLP-1R agonist retatrutide (LY3437943), the cagrilintide/semaglutide (CagriSema) 2.4 mg combination, high-dose oral semaglutide, and oral orforglipron are in advanced stages of development...Liraglutide, semaglutide and tirzepatide are incretin-based therapies currently approved by FDA for the management of obesity, while triple GIPR/GCGR/GLP-1R agonist retatrutide (LY3437943), the cagrilintide/semaglutide (CagriSema) 2.4 mg combination, high-dose oral semaglutide, and oral orforglipron are in advanced stages of development...Moreover, incretin-based therapies have also been proven beneficial on obesity-related comorbidities, such as knee osteoarthritis (KOA), obstructive sleep apnea (OSA) syndrome, and MASLD. Further research is needed to improve our understanding of their effects on obesity-related comorbidities and the..."

Cardiovascular • Congestive Heart Failure • Diabetes • Genetic Disorders • Heart Failure • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Obstructive Sleep Apnea • Osteoarthritis • Pain • Respiratory Diseases • Rheumatology • Sleep Disorder • Type 2 Diabetes Mellitus

Eli Lilly's first weight loss pill could expand access to GLP-1s around the globe, executive says (Yahoo Finance) - "Orforglipron is currently in a phase 3 trial....Eli Lilly CEO Dave Ricks told Bloomberg News in January that phase 3 trial results are expected before the middle of 2025. That could lead to regulatory approval for the drug in 2026."

Approval • P3 data • Obesity • Type 2 Diabetes Mellitus

Glucagon-like peptide-1 receptor agonists: a new pharmacological treatment option for psychiatric illnesses? (PubMed, Nervenarzt) - "Albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, orforglipron and semaglutide are glucagon-like peptide‑1 (GLP-1) receptor agonists. Tirzepatide targets not only GLP‑1 but also glucose-dependent insulinotropic peptide (GIP) receptors and retatrutide is a triple GLP‑1, GIP and glucagon receptor agonist...Typical accompanying adverse reactions are gastrointestinal side effects, such as nausea, vomiting, diarrhea, eructation and gastroesophageal reflux. More severe side effects include pancreatitis, allergic reactions, renal function disorders and possibly an increased risk of thyroid cancer."

Journal • Review • Addiction (Opioid and Alcohol) • Allergy • Alzheimer's Disease • Binge Eating Disorder • Cardiovascular • CNS Disorders • Cognitive Disorders • Dementia • Depression • Diabetes • Endocrine Cancer • Gastroenterology • Gastroesophageal Reflux Disease • Gastrointestinal Disorder • Mental Retardation • Metabolic Disorders • Mood Disorders • Oncology • Pancreatitis • Psychiatry • Solid Tumor • Thyroid Gland Carcinoma

A Study to Compare Tablets and Capsules of Orforglipron (LY3502970) in Healthy Participants Who Are Obese or Overweight (clinicaltrials.gov) - P1 | N=508 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

A Drug-Drug Interaction Study of Orforglipron (LY3502970) With Quinidine in Healthy Participants (clinicaltrials.gov) - P1 | N=27 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Trial completion

A Study of Orforglipron (LY3502970) to Compare a Single Capsule and Multiple Capsules in Healthy Participants (clinicaltrials.gov) - P1 | N=80 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed

Eli Lilly bets big on weight-loss pill with $550 million inventory stockpile (The Economic Times) - "Eli Lilly is betting big on its experimental oral weight-loss drug even before reporting data from its late-stage trial by recording nearly $550 million in 'pre-launch inventory' in its financial statements, a filing showed on Wednesday...The move is unusual as it comes more than a year before the drug orforglipron, is expected to be launched....Lilly also said on its post-earning conference call this month that it was already building manufacturing capacity for the drug."

Commercial • Launch • Obesity

Comparative efficacy and safety of GLP-1 receptor agonists for weight reduction: A model-based meta-analysis of placebo-controlled trials. (PubMed, Obes Pillars) - "The FDA has approved glucagon-like peptide-1 (GLP-1) receptor agonists such as Liraglutide, Semaglutide, and the GLP-1/gastric inhibitory polypeptide (GIP) dual agonist Tirzepatide for the treatment of obesity...The maximum weight reduction effect ranged from 4.25 kg (Liraglutide) to 22.6 kg (Retatrutide). Reported onset times ranged from 6.4 weeks (Orforglipron) to 19.5 weeks (Tirzepatide)...Common adverse events of GLP-1RAs, reported in the literature include nausea, vomiting, diarrhea, and constipation, with a significantly higher incidence of nausea than that of placebo. This study provides a quantitative evaluation of the efficacy and safety of GLP-1RAs and offers valuable insights into the assessment of new drugs for weight reduction."

Clinical • Journal • Retrospective data • Constipation • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Obesity • GCG

Emerging pharmacotherapies for obesity: A systematic review. (PubMed, Pharmacol Rev) - "Oral semaglutide 50 mg is the only medication that has completed a phase 3 trial. There are 14 ongoing phase 3 trials on glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) (ecnoglutide, orforglipron, and TG103), GLP-1 RA/amylin agonist (CagriSema), GLP-1/glucagon RAs (mazdutide and survodutide), GLP-1/glucose-dependent insulinotropic polypeptide and glucagon RA (retatrutide), dapagliflozin, and the combination sibutramine/topiramate...This systematic review identifies the state and mechanism of action of emerging pharmacotherapies undergoing or having completed phase 2 and phase 3 clinical trials. The information provided herein furthers the understanding of obesity management, implying direct clinical implications and stimulating research initiatives."

Journal • Review • Genetic Disorders • Obesity

A Study of Orforglipron (LY3502970) in Adult Participants with Obesity or Overweight (clinicaltrials.gov) - P1 | N=120 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P1 trial • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity

Orforglipron: Data from P3 ATTAIN-1 trial (NCT05869903) for obesity in 2025 (Eli Lilly) - Q4 2024 Results: Data from P3 ATTAIN-2 trial (NCT05872620) for obesity in 2025

P3 data • Obesity

Orforglipron: Regulatory submission in US/EU/Japan for obesity in 2025 (Eli Lilly) - Q4 2024 Results

EMA filing • FDA filing • Japan filing • Obesity

Orforglipron: Primary completion and completion of P3 ATTAIN-2 trial (NCT05872620) for obesity in Aug 2025 (Eli Lilly) - Q4 2024 Results: Primary completion and completion of P3 ATTAIN-MAINTAIN trial (NCT06584916) for obesity in Jan 2026

Trial completion date • Trial primary completion date • Obesity

Orforglipron: Primary completion of P3 trial (NCT06672939) in adolescents with obesity in Feb 2027 (Eli Lilly) - Q4 2024 Results: Completion of P3 trial in adolescents with obesity in Mar 2027; Primary completion of P3 ATTAIN-OSA trial (NCT06649045) in participants with obstructive sleep apnea and obesity in Nov 2026; Completion of P3 trial in participants with obstructive sleep apnea and obesity in Jan 2027

Trial completion date • Trial primary completion date • Obesity • Obstructive Sleep Apnea