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

Comparative Efficacy and Safety of Newly FDA-Approved Oral Orforglipron Versus Injectable GLP-1, Dual-, and Triple-Agonist Therapies: A Systematic Review and Bayesian Network Meta-Analysis (ACG 2026) - "Introduction: Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are major contributors to the global gastrointestinal disease burden. 24 RCT's comprising 14,240 patients were included, including 8,412 females (59.1%) and 5,828 males (40.9%). Treatment arms included oral orforglipron (n=3,120), semaglutide (n=3,450), tirzepatide (n=2,880), liraglutide (n=1,850), retatrutide (n=1,680), and survodutide (n=1,260). Mean baseline BMI ranged from 36.1â38.1 kg/m² and HbA1c from 7.9â8.3%."

Retrospective data • Review • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

NHRA licences "Foundayo" for obesity treatment (GDNonline.com) - "The licensing allows 'Foundayo' to enter the Bahraini market through pharmacies, provided it is used according to approved medical guidelines and following the necessary medical consultation, ensuring its safe use based on the patient’s health condition...The approval of the medication represents an important step in expanding obesity treatment options and addressing related health challenges, in line with global developments in the treatment of obesity and associated chronic diseases."

Approval • Obesity

GLP-1 receptor agonists and ocular safety- Pharmacokinetic insights into ischemic optic neuropathy and diabetic retinopathy risk: A review. (PubMed, Biomol Biomed) - "Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed the management of type 2 diabetes mellitus and obesity, but their expanding use has raised concerns about ocular safety...The most consistent NAION signal involved high-exposure subcutaneous semaglutide, whereas findings for oral semaglutide, liraglutide, dulaglutide, exenatide, and tirzepatide were absent, inconsistent, or weaker...Semaglutide 7.2 mg, with an estimated Css of approximately 230 nmol/L, and highly bioavailable oral orforglipron warrant formulation-specific postmarketing ocular surveillance, although direct evidence of NAION risk remains unavailable. Current evidence does not support class-wide prescribing restrictions. An individualized approach considering patient-specific ocular risk, agent, formulation, and dose is more appropriate, while prospective studies with standardized ophthalmic endpoints are needed to establish causality and validate pharmacokinetic and pharmacogenomic..."

Journal • PK/PD data • Review • Diabetes • Diabetic Neuropathy • Diabetic Retinopathy • Genetic Disorders • Metabolic Disorders • Obesity • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain • Retinal Disorders • Type 2 Diabetes Mellitus

ATTAIN-NOW: A Study of Orforglipron in Participants With Overweight at Risk of Development of Obesity-Related Complications or Progression to Class 1 Obesity (clinicaltrials.gov) - P3 | N=2001 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Genetic Disorders • Hypertension • Obesity

Select Lilly Presentations at EASD 2026 (PRNewswire) - "TRIUMPH-2: Adults with obesity or overweight and type 2 diabetes taking retatrutide lost up to an average of 49.6 lbs (22.5 kg; 20.8%) and lowered their A1C by up to an average of 1.6% at 80 weeks...This EASD-sponsored symposium on amylins in diabetes will feature Phase 2 results for eloraTZP, an investigational combination of eloralintide and tirzepatide, in adults with obesity or overweight and type 2 diabetes....ACHIEVE-4: Foundayo demonstrated non-inferiority versus insulin glargine, with a 16% lower risk of MACE-4 events (HR: 0.84; 95.0% CI: 0.59 to 1.20) and a 23% lower risk of MACE-3 events (HR: 0.77 95.0% CI: 0.52 to 1.13), in adults with type 2 diabetes and obesity or overweight at increased cardiovascular risk."

P2 data • P3 data • Obesity • Type 2 Diabetes Mellitus

Select Lilly Presentations at EASD 2026 (PRNewswire) - "ACHIEVE-2/ACHIEVE-3 Time-to-Goal Analysis: Foundayo 17.2 mg helped adults with type 2 diabetes reach their A1C target and body weight loss goals faster than dapagliflozin and oral semaglutide 7 mg and 14 mg; ATTAIN-1 Physical and Psychosocial Functioning: In adults with obesity or overweight and at least one weight-related medical problem, Foundayo improved both physical and psychosocial functioning versus placebo...Zepbound 10 mg and 15 mg were associated with distinct changes in the plasma proteome compared with semaglutide 1.7 mg and 2.4 mg, offering early biological insight into the differences in cardiometabolic benefit observed between the two therapies in the head-to-head SURMOUNT-5 trial."

P3 data • Obesity • Type 2 Diabetes Mellitus

Orforglipron: An Oral GLP-1 Receptor Agonist for Obesity Treatment. (PubMed, Ann Pharmacother) - "Orforglipron is a potentially useful addition for the treatment of obesity, but it still requires additional data on efficacy in treatment of obesity-related comorbidities for full comparison."

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

Preferences for Obesity Medications Among People With Overweight or Obesity in the United States: A Discrete-Choice Experiment (OPTIC). (PubMed, Diabetes Obes Metab) - "Individuals with overweight or obesity prioritise weight-loss efficacy, CV risk reduction, and oral administration in OM treatment decisions; dosing instruction requirements were of low importance."

Journal • Cardiovascular • Genetic Disorders • Obesity

Predicting the Long-Term Risk of Type 2 Diabetes and Cardiovascular Disease With Orforglipron in People With Overweight or Obesity: A Post Hoc Analysis of the ATTAIN-1 Trial. (PubMed, Diabetes Obes Metab) - P3 | "In this post hoc analysis, once-daily oral orforglipron was associated with statistically significant improvements in predicted 10-year risk of incident T2D and CVD compared with placebo over 72 weeks using three validated risk prediction models."

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

Efficacy and safety of orforglipron 12 mg versus orforglipron 36 mg maintenance dose among patients with obesity with or without diabetes: a systematic review and comprehensive meta-analysis. (PubMed, BMC Endocr Disord) - "In obese adults, orforglipron 36 mg improved weight and metabolic outcomes compared with 12 mg. No statistically significant differences between doses were detected for the prespecified safety outcomes, although small increases in ALT and AST were observed with the 36 mg dose and the trials included were not powered to detect rare or long-term adverse events. These findings support consideration of the higher maintenance dose when clinically appropriate. Longer-term studies are needed to confirm the benefit and cardiovascular outcomes."

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

Oral small-molecule GLP-1 receptor agonists: a new Frontier in cardiometabolic medicine. (PubMed, Front Pharmacol) - "Unlike oral semaglutide, which delivers a peptide via sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC)-mediated absorption with stringent dosing requirements, small-molecule GLP-1 RAs evade enzymatic degradation and facilitate once-daily oral dosing without fasting restrictions or cold-chain logistics. This review synthesizes the pharmacology, Phase 3 clinical evidence (including the ACHIEVE and ATTAIN programs), comparative efficacy against injectable GLP-1 RAs and SGLT2 inhibitors, safety data from over 11,000 patients, and the evolving regulatory landscape-including FDA approval of orforglipron (Foundayo) for chronic weight management in April 2026. We explore positioning within the cardiometabolic treatment algorithm, emphasize limits of indirect comparisons, identify the unresolved cardiovascular outcomes question linked to biased partial agonism, and discuss implications for global access."

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

A frequentist network meta-analysis of bariatric surgery versus next-generation injectable and oral incretins for cardiometabolic disease (EASD 2026) - "Materials and A frequentist network meta-analysis was conducted synthesizing data from surgical RCTs (Roux-en-Y Gastric Bypass [RYGB], Sleeve Gastrectomy [SG]) and Phase 2/3 trials of advanced pharmacotherapies (tirzepatide, retatrutide, survodutide, CagriSema, and orforglipron)... When pooling estimates across broad metabolic populations, next-generation incretins successfully bridge the placebo- adjusted efficacy gap to bariatric surgery. The most potent injectable multi-agonists match the absolute mass offloading of sleeve gastrectomy, while accessible daily oral small molecules rival legacy surgical banding."

Bariatric surgery • Retrospective data • Surgery • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists and Co-agonists for Weight Loss Among Adults Without Diabetes : An Updated Systematic Review. (PubMed, Ann Intern Med) - "To update our prior systematic review evaluating the efficacy and safety of GLP-1 RAs and co-agonists among adults with overweight or obesity without diabetes...Among commercially available therapies, placebo-subtracted weight loss reached up to -5.8% (95% CI, -8.0% to -3.6%) for liraglutide, -14.8% (CI, -16.2% to -13.4%) for subcutaneous semaglutide, -14.3% (CI, -17.2% to -11.4%) for oral semaglutide, -12.4% (CI, -15.1% to -9.7%) for orforglipron, and -19.0% (CI, -21.6% to -16.4%) for tirzepatide. Numerically greater placebo-subtracted reductions were seen with emerging multiagonists, including -23.9% (CI, -29.3% to -18.5%) with amycretin and -22.1% (CI, -24.9% to -19.3%) with retatrutide...Head-to-head data showed greater weight loss with semaglutide and JNJ-64565111 than liraglutide and greater weight loss with tirzepatide and cagrilintide-semaglutide (CagriSema; Novo Nordisk) than semaglutide...None. (PROSPERO: CRD42024505558)."

Journal • Review • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity

Oral orforglipron 17.2 mg versus oral semaglutide 25 mg in adults with type 2 diabetes and BMI ≥25kg/m2: an indirect treatment comparison (EASD 2026) - P3 | "Materials and ACHIEVE-3, a 52-week randomized, open-label, active-controlled, multinational phase 3 study, enrolled adults ≥18 years with T2D on metformin (≥1500 mg/day), HbA 1c 7.0-10.5%, and BMI ≥25 kg/m². In this indirect treatment comparison, OFG 17.2 mg was associated with greater reductions in BW and HbA 1c versus SEMA 25 mg in adults with inadequately controlled T2D and overweight or obesity. While the magnitude of the treatment difference is statistically significant, the clinical meaningfulness needs to be further explored through long term health outcomes. Further, direct comparative studies are needed to confirm the treatment differences."

Clinical • Late-breaking abstract • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Reasons for Orforglipron Initiation and Treatment Goals: Interim Results from the FOUNDERS Survey (OBESITY WEEK 2026) - No abstract available

Orforglipron Induces Weight Loss and Activates Appetite-Suppressing Brain Regions in a HGLP-1R Model (OBESITY WEEK 2026) - No abstract available

Oral Semaglutide Versus Orforglipron in Obesity: A Short-Term Cost-of-Control Evaluation (ORACLE) (OBESITY WEEK 2026) - No abstract available

Genetic Disorders • Obesity

Patients Reported Orforglipron Was Simple, Convenient, Easy to Use: Results from the FOUNDERS Survey (OBESITY WEEK 2026) - No abstract available

Clinical

Eating Control and Food Cravings After Transition from Injectable Incretin Therapy to Orforglipron (OBESITY WEEK 2026) - No abstract available

Genetic Disorders • Obesity

RV-8451, a Pre-Clinical, Muscle-Preserving GLP-1R NPA, Outperforms Orforglipron in Obesity Models (OBESITY WEEK 2026) - No abstract available

Preclinical • Genetic Disorders • Obesity

Humanized GLP-1R Mice Enable Translational Evaluation of Orforglipron With Reduced Energy Intake and Improved Glucose Tolerance (OBESITY WEEK 2026) - No abstract available

Preclinical

Corporate Supported Symposium - Weight Management Foundayo (OBESITY WEEK 2026) - "Attendees will have the opportunity to ask questions at the conclusion of the program. Learning Objectives 1 Summarize the safety and efficacy data for this treatment 2 Identify appropriate adult patients 3 Provide strategies for initiating and maintaining treatment"

Genetic Disorders • Obesity

ATTAIN-OSA: A Master Protocol for Orforglipron in Participants With Obstructive Sleep Apnea and Obesity or Overweight (clinicaltrials.gov) - P3 | N=712 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed | Trial completion date: Jan 2027 ➔ Jul 2026 | Trial primary completion date: Nov 2026 ➔ Jul 2026

Trial completion • Trial completion date • Trial primary completion date • Genetic Disorders • Obesity • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Obstructive sleep apnea, GLP-1 receptor agonist pharmacotherapy, and the oral microbiome: competing biological influences and implications for oral health monitoring. (PubMed, Clin Oral Investig) - "GLP-1RA pharmacotherapy in OSA creates a biologically complex oral microbiome environment whose clinical trajectory cannot be predicted from current evidence. Prospective studies are warranted, oral health monitoring beginning at treatment initiation is scientifically justified, and seven priority research questions are identified at the convergence of sleep medicine, endocrinology, and oral biology."

Journal • Review • Endocrine Disorders • Gastroenterology • Gastroesophageal Reflux Disease • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Lilly says Foundayo has captured over 30% of new US patients on oral weight-loss drugs (Reuters) - "Investors are closely tracking demand for oral obesity drugs, which ​could expand the weight-loss market by appealing to patients reluctant ⁠to use injections and easing some supply challenges associated with injectable therapies. Novo ​said in January it expects oral drugs to make up more than a ​third of GLP-1 weight-loss treatment use by 2030. Analysts expect the overall obesity treatment market to hit over $100 billion annually in the U.S. alone by that year. Lilly's injectable GLP-1 obesity ​treatment Zepbound has also seen preference among patients in the U.S. government's ​Medicare obesity drug pilot launched in July."

Commercial • Obesity