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

ACHIEVE-J: A Long-term Safety Study of Orforglipron (LY3502970) in Participants With Type 2 Diabetes (clinicaltrials.gov) - P3 | N=466 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

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

Cellular Characterisation of Signalling and Receptor Trafficking Induced by MET-097, a G Protein-Biased GLP-1R Agonist (ADA 2025) - "We aimed to further elucidate the signalling and trafficking profile of MET-097. In vitro BRET-based biosensors were used to compare clinically relevant GLP-1R agonists. Compared to reference agonists (GLP-1/exendin-4/semaglutide), MET-097 acted as a partial agonist for Gαs and Gαq recruitment at both the plasma membrane (36% and 22% of exendin-4) and endosomal compartments (34% and 37% of exendin-4), yet still showed full cAMP response (115% of exendin-4). We speculate the pharmacological attributes of MET-097 may contribute to a unique pharmacodynamic profile. Of particular interest will be to align these attributes with the efficacy and tolerability observed in clinical trials."

Metabolic Disorders • Obesity • ARRB1

Incretin-based therapies for the treatment of obesity-related diseases. (PubMed) - "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 underlying mechanism, whether involving direct effects on target tissues or mediated by improvement in BW, glucose levels and other CV risk factors."

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

Development and characterisation of a humanised GLP-1 receptor mouse model for the evaluation of small molecule GLP1R agonists (EASD 2025) - "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 • Metabolic Disorders • Obesity • FOS

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

Enrollment open • Cardiovascular • Genetic Disorders • Hypertension • Obesity

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

Enrollment open • Cardiovascular • Genetic Disorders • Hypertension • Obesity

A Study of Orforglipron (LY3502970) in Participants With Obesity or Overweight and Type 2 Diabetes (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

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

A Study to Compare Tablets and Capsules of Orforglipron (LY3502970) in Healthy Participants Who Are Obese or Overweight (clinicaltrials.gov) - P1 | N=533 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Obesity

A Study of Orforglipron (LY3502970) to Compare a Single Capsule and Multiple Capsules in Healthy Participants (clinicaltrials.gov) - P1 | N=86 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Trial completion

Development and Characterization of a Humanized GLP-1 Receptor Mouse Model for the Evaluation of Small-Molecule GLP1R Agonists (ADA 2025) - "These findings validate the Gubra hGLP1R mouse as a relevant preclinical model to advance preclinical development of small-molecule GLP1RAs for the treatment of obesity and related metabolic disorders."

Late-breaking abstract • Preclinical • Diabetes • Metabolic Disorders • Obesity

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

Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes. (PubMed, N Engl J Med) - P3 | "In adults with early type 2 diabetes, orforglipron significantly reduced the glycated hemoglobin level over a period of 40 weeks. (Supported by Eli Lilly; ACHIEVE-1 ClinicalTrials.gov number, NCT05971940.)."

Journal • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Lilly's oral GLP-1, orforglipron, showed compelling efficacy and a safety profile consistent with injectable GLP-1 medicines, in complete Phase 3 results published in The New England Journal of Medicine (Eli Lilly Press Release) - "Later this year, Lilly expects to share topline results from ACHIEVE-2, evaluating orforglipron compared with dapagliflozin, and ACHIEVE-3, evaluating orforglipron compared to oral semaglutide, both in adults with type 2 diabetes inadequately controlled with metformin. ATTAIN-1 and ATTAIN-2, evaluating orforglipron for weight management, will also be shared in the third quarter of this year."

Clinical data • Obesity • Type 2 Diabetes Mellitus

Lilly's oral GLP-1, orforglipron, showed compelling efficacy and a safety profile consistent with injectable GLP-1 medicines, in complete Phase 3 results published in The New England Journal of Medicine (Eli Lilly Press Release) - P3 | N=559 | ACHIEVE-1 (NCT05971940) | Sponsor: Eli Lilly and Company | "Eli Lilly and Company...announced detailed results from ACHIEVE-1, a Phase 3 trial evaluating the safety and efficacy of orforglipron compared to placebo in adults with type 2 diabetes and inadequate glycemic control with diet and exercise alone...In the study, orforglipron met the primary endpoint of superior A1C reduction compared to placebo at 40 weeks, lowering A1C by 1.3% to 1.6% from a baseline of 8.0%, for the efficacy estimand. In key secondary endpoints, up to 76.2% of participants taking orforglipron achieved the ADA treatment target A1C of <7%, 66.0% achieved an A1C of ≤6.5%, and 25.8% achieved <5.7%, defined as a normal A1C value. Improvements in A1C were observed as early as four weeks and were accompanied by similar reductions in fasting serum glucose."

P3 data • Type 2 Diabetes Mellitus

Eli Lilly (LLY) to Reveal Key Phase 3 Trial Results for Orforglipron (Gurufocus) - "Eli Lilly...is gearing up to announce groundbreaking results from its ACHIEVE-1 Phase 3 trial. This study focuses on orforglipron, an innovative oral weight loss drug designed for adults grappling with type 2 diabetes. The data, which will be disclosed during the American Diabetes Association's Scientific Sessions on June 21, highlights an average weight reduction of approximately 8% over a 40-week period. This promising development underscores Eli Lilly's commitment to addressing critical health challenges."

P3 data • Obesity • Type 2 Diabetes Mellitus

Treatment with orforglipron, an oral glucagon like peptide-1 receptor agonist, is associated with improvements of CV risk biomarkers in participants with type 2 diabetes or obesity without diabetes. (PubMed, Cardiovasc Diabetol) - P2 | "Orforglipron treatment was associated with beneficial changes in CV risk markers in participants with T2D and in participants with overweight/obesity without T2D. (Clinicaltrials.gov: NCT05048719, NCT05051579)."

Biomarker • Clinical • Journal • Cardiovascular • Diabetes • Dyslipidemia • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • APOB • CRP • IL6

Treatment with orforglipron, an oral glucagon like peptide-1 receptor agonist, is associated with improvements of CV risk biomarkers in participants with type 2 diabetes or obesity without diabetes (Biomed Central) - P=NA | N=NA | "Significant placebo-adjusted decreases from baseline in blood pressure, low-density lipoprotein (LDL) cholesterol, triglycerides, ApoB, ApoC3, and hsCRP were observed following orforglipron treatment in participants with T2D and/or overweight or obesity. In both studies, improvements in blood pressure, lipid parameters, and most of the evaluated biomarkers were of similar magnitude after treatment with 12 mg orforglipron as with 24, 36, and 45 mg."

Clinical data • Obesity • Type 2 Diabetes Mellitus

A Study of Orforglipron (LY3502970) in Participants With Obesity or Overweight and at Least One Weight-Related Comorbidity (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

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

A Master Protocol for Orforglipron (LY3502970) in Participants With Obesity or Overweight With and Without Type 2 Diabetes (clinicaltrials.gov) - P3 | N=1200 | Recruiting | Sponsor: Eli Lilly and Company

New P3 trial • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Orforglipron Impovered Markers of Beta-Cell Function and Insulin Sensitivity in Type 2 Diabetes (DDG 2025) - "How does Orforlipron (OFG) IMPRONE Markers of Beta-Cell Function and Insulin Sensitivity in Comparison to Dulaglutide (Dula) in Patients With Type 2 Diabetes (T2D)?...Participants with T2D (Mean Age, 58.9 Years; Baseline HBA1C, 8.1%; Weight, 100.3 kg) Treated with Diet and Exercise, With/Without Metformin, Were Randomized to PBO, du 1.5 mg, or once-daily Ofg 3, 12, 36, or 45 mg... Thesis Analyses Suggest Improved Glycemic Control with VS Du May Be Partly Explained by Improved β-Cell Function and Insulin Sensitivity. Additional studies are ongoing to understand thesis Mechanisms."

Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

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

Enrollment open • Cardiovascular • Genetic Disorders • Hypertension • Obesity

A Study of Orforglipron (LY3502970) in Participants With Obesity or Overweight and at Least One Weight-Related Comorbidity (clinicaltrials.gov) - P3 | N=600 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P3 trial • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

A Study of Orforglipron (LY3502970) in Participants With Obesity or Overweight and Type 2 Diabetes (clinicaltrials.gov) - P3 | N=600 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P3 trial • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

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