Zepbound (tirzepatide) / Eli Lilly - LARVOL DELTA

Trends in GLP-1 Receptor Agonist Prescribing Without an Apparent FDA-Approved Indication. (PubMed, Obesity (Silver Spring)) - "GLP-1 receptor agonist prescribing without an apparent FDA-approved indication has increased rapidly and disproportionately involves socioeconomically advantaged populations, including individuals without obesity. The risk-benefit profile in these populations remains uncertain."

FDA event • Journal • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Diabetes • Dyslipidemia • Genetic Disorders • Heart Failure • Hypertension • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Duodenal Neuroendocrine Tumor Revealed by Escherichia coli Bacteremia: Possible Implication of Tirzepatide (ACG 2026) - "Case Description/ A 62-year-old female with known history of hypertension, hyperlipidemia and obesity, for which she was initially on liraglutide then switched to tirzepatide two months prior to admission...The Patient was diagnosed with sepsis and started immediately on piperacillin tazobactam...The patient received pantoprazole 40 mg twice daily and sucralfate, resulting in improvement of abdominal pain...In our patient, the ulcer likely contributed actively to the translocation, especially in the neoplastic conditions. Figure: Duodenal Bulbar Ulcer With Pigmented Material"

Cardiovascular • Dyslipidemia • Endocrine Cancer • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Hepatology • Hypertension • Immunology • Infectious Disease • Neuroendocrine Tumor • Obesity • Oncology • Peptic Ulcer • Septic Shock • Solid Tumor

Does Glucagon Like Peptide Receptor Agonist Increase the Risk of Peptic Ulcer Disease? A Wide National Retrospective Matched Cohort Study (ACG 2026) - "Introduction: Glucagon like Peptide Receptor agonist (GLP1RA) are increasingly used for management of obesity and type 2 diabetes mellitus... A total of 17,230 patients on GLP1RA were identified and propensity matched with 17,230 patients who were not on GLP1RA. PUD occurred in 7.3% of patients taking GLP1RA, compared to 5.9% of matched controls (Hazard Ratio (HR) = 1.11, 95% CI: [1.02-1.20]). Therefore, the GLP1RA was associated with statistically significant increased risk of PUD."

Retrospective data • Diabetes • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Metabolic Disorders • Obesity • Peptic Ulcer • Type 2 Diabetes Mellitus

Trends in Endoscopic Sleeve Gastroplasty Utilisation Among Patients With Obesity, Overweight, and Diabetes: A Multi-Institutional Retrospective Analysis Over 5 Years (ACG 2026) - "GLP-1 RA use post ESG was dominated by semaglutide (8%), liraglutide (4%), dulaglutide (4%) and tirzepatide (2%) as in table 2... A total of 5,201 patients with DM, Obesity and overweight underwent ESG which was predominantly utilized by middle-aged White, non-Hispanic females with mean age around 56 years. ESG recipients demonstrated a substantial burden of cardiometabolic disease, including diabetes, hypertension, ischemic heart disease and also GERD and Gastritis. Baseline characteristics and other associated comorbidities are described in table 1."

Retrospective data • Cardiovascular • Coronary Artery Disease • Diabetes • Gastroesophageal Reflux Disease • Gastrointestinal Disorder • Genetic Disorders • Heart Failure • Hypertension • Metabolic Disorders • Obesity

GLP-1 and Dual GIP/GLP-1 Receptor Agonists in Pediatric Obesity: From Neuroendocrine Mechanisms to Clinical Application. (PubMed, Int J Mol Sci) - "Randomized pediatric trials demonstrate clinically meaningful BMI reduction with liraglutide and semaglutide, with the largest mean effect reported for semaglutide in adolescents; however, long-term effects on growth, puberty, bone health, body composition, and weight maintenance remain uncertain...Incretin-based therapies should be integrated with nutritional, behavioral, psychological, and family-based care. Their future value will depend on durable efficacy, developmental safety, equitable access, and identification of patients most likely to benefit."

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

Cost-Effectiveness of Metformin, Injectable Tirzepatide, and Oral Semaglutide for Patients with Knee Osteoarthritis and Obesity (ACR Convergence 2026) - No abstract available

Clinical • Cost effectiveness • HEOR • Genetic Disorders • Immunology • Obesity • Osteoarthritis • Rheumatology

Real-World Discontinuation of GLP-1âBased Therapies for Obesity: A Systematic Review and Meta-Analysis (ACG 2026) - "Thirty-eight studies (N=307,190 patients) were included. At 6 months, the pooled discontinuation incidence for all agents was 47% (95% CI 38-57%). Discontinuation differed by agent: liraglutide 52%, semaglutide 46%, and tirzepatide 35% (p=0.04; Figure 1)."

Real-world • Real-world evidence • Retrospective data • Review • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Comparative Efficacy and Safety of Incretin-Based Therapies, FGF21 Analogs, and Pan-PPAR Agonists for MASH: A Systematic Review and Bayesian Network Meta-Analysis (ACG 2026) - "Introduction: Metabolic dysfunctionâassociated steatohepatitis (MASH) is an increasing global health burden with limited approved therapies... A total of 14 RCT's comprising 8,462 patients were included, with 53.1% males and 46.9% females. Patients received semaglutide (n=1,642), tirzepatide (n=1,128), survodutide (n=612), retatrutide (n=318), efruxifermin (n=742), pegozafermin (n=512), lanifibranor (n=247), resmetirom (n=2,955), or placebo/standard therapy (n=306). Baseline age, BMI, diabetes prevalence, ALT, and fibrosis stages were comparable."

Retrospective data • Review • Diabetes • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

A Case of Ischemic Colitis in a 39-Year-Old Man on GLP-1 Therapy (ACG 2026) - "Case Description/ A 39-year-old male with obesity on tirzepatide presented with sudden-onset severe abdominal pain and multiple episodes of hematochezia...He was admitted for intravenous fluids and started on empiric piperacillinâtazobactam...Close outpatient follow-up is crucial to detect early warning signs, prevent progression, and reduce hospitalization rates related to medication side effects. Figure: Colonoscopy images Figure: Colonoscopy images"

Clinical • Atherosclerosis • Cardiovascular • Constipation • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Hepatology • Immunology • Inflammation • Inflammatory Bowel Disease • Obesity • Pancreatitis • Vasculitis

Association Between GLP-1 Receptor Agonist Exposure and Acute Pancreatitis Risk in Patients With Cholelithiasis: A Real-World Cohort Study (ACG 2026) - "Introduction: GLP-1 receptor agonists (GLP-1 RAs) are widely used for type 2 diabetes and obesity...Adults (â¥18 years) with cholelithiasis who were exposed to GLP-1 RAs (semaglutide, dulaglutide, liraglutide, exenatide, tirzepatide) were compared to unexposed patients... 162,458 patients were included per cohort. For the primary outcome, 152,331 vs 151,712 patients were compared, and acute pancreatitis occurred in 2,172 (1.43%) vs 2,979 (1.96%) (RD -0.54%, 95% CI -0.63 to -0.45%; RR 0.73, 95% CI 0.69-0.76; HR 0.64, 95% CI 0.61-0.68; p< 0.001). 158,091 vs 158,395 patients were compared for the secondary outcome and gallstone pancreatitis occurred in 998 (0.63%) vs 1,745 (1.102%) (RD -0.47%, 95% CI -0.54 to -0.41%; RR 0.57, 95% CI 0.53-0.62; p< 0.001) (Table 1)."

Clinical • Real-world • Real-world evidence • Diabetes • Gastroenterology • Genetic Disorders • Metabolic Disorders • Obesity • Pancreatitis • Type 2 Diabetes Mellitus

Weekly GLP-1 Receptor Agonists in Obese Individuals Without Diabetes (clinicaltrials.gov) - P3 | N=150 | Completed | Sponsor: Zagazig University

New P3 trial • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity

Clinical Outcomes Associated With GLP-1 Receptor Agonist Therapy in Patients With Type 2 Diabetes and Short Bowel Syndrome Receiving Total Parenteral Nutrition (ACG 2026) - "A total of 6,047 patients with T2DM and SBS on TPN 18 years old or older were identified, 1,277 of these individuals were on GLP -1 RAs; 1,152 out of those 1,277 (mean [SD] age, 55.5 [11.0] years; 889 [77.2%] female) were matched with 1,152 individuals (mean [SD] age, 55.8[13.7] years; 897 [77.9%] female) who did not take GLP-1 RAs. The GLP-1 RAs group was associated with lower rates of hospitalization (HR, 0.57; 95% CI, 0.50-0.64), ED visits (HR, 0.82; 95% CI, 0.73-0.93), all-cause mortality (HR, 0.48; 95% CI, 0.33-0.69), dehydration (HR, 0.45; 95% CI, 0.31-0.66), AKI (HR, 0.61; 95% CI, 0.41-0.91), malnutrition (HR, 0.57; 95% CI, 0.41-0.79), weight loss (HR, 0.49; 95% CI, 0.30-0.80) and TPN dependence (HR, 0.61; 95% CI, 0.44-0.85), when compared with the non-GLP-1 agonist group. No difference was found in intestinal obstruction and ileus when comparing groups."

Clinical • Clinical data • Diabetes • Gastrointestinal Disorder • Metabolic Disorders • Short Bowel Syndrome • Type 2 Diabetes Mellitus

Tirzepatide-Associated Drug-Induced Liver Injury in a Liver Transplant Recipient: A Case Report (ACG 2026) - "She has been on 5 mg of extended-release tacrolimus (envarsus) daily with stable therapeutic trough levels. Review of other medications was notable for allopurinol, escitalopram, and glipizide, which were long-term with stable dose...Figure: Table 1. Liver Enzyme Trends During Tirzepatide Exposure and Following Discontinuation"

Case report • Clinical • Diabetes • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • Transplantation • Type 2 Diabetes Mellitus

Comparative Efficacy of Endoscopic Sleeve Gastroplasty and Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss: Systematic Review and Meta-Analysis (ACG 2026) - "Three studies (1 RCT and 2 retrospective cohorts) were included. Semaglutide was used in two of the studies, while liraglutide and tirzepatide were used in one study each. The ESG group comprised 265 patients (mean age 45.5; 29.8% males), while the GLP1RA group included 141 patients (mean age 52.6; 27.7% male)."

Retrospective data • Review • Diabetes • Gastrointestinal Disorder • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

Glucagon-Like Peptide-1 Receptor Agonists and the Risk of Colorectal Cancer Among Adults With Obesity: A Multicenter Real-World Cohort Study (ACG 2026) - "After matching,1,340,395 adults remained in each cohort achieving demographic balance(mean age 52 years; 66% female; 69% White,19% Black & 2% Asian).GLP-1RA exposure was associated with a 67.5% lower risk of composite CRC with significant reductions in CC(RR 0.495,95% CI 0.479â0.512) and RC(0.411,0.386â0.437).Associations remained significant in adults< 45 years with particularly pronounced reduction in RC(0.289, 0.214â0.389) & CC(0.428, 0.358â0.512).Findings were consistent across BMI strata and among individuals with concomitant obesity and diabetes.Drug-specific analyses with semaglutide,tirzepatide & dulaglutide demonstrated significant reductions in both CC and RC risk.Liraglutide was associated with lower RC risk, whereas no significant associations were observed with exenatide. Myopia, used as a negative control outcome demonstrated a near-null association In this large real-world cohort of adults with obesity, GLP-1RA use was..."

Clinical • Real-world • Real-world evidence • Colon Cancer • Colorectal Cancer • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Oncology • Ophthalmology • Solid Tumor

Differential Risk of Acute Appendicitis With Semaglutide Versus Tirzepatide: A Propensity-Matched Analysis of Million Patients (ACG 2026) - "Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and the dual GIP/GLP-1 agonist tirzepatide are increasingly used for type 2 diabetes and obesity, but concerns have been raised about a potential association with acute appendicitis... Baseline characteristics were well balanced across all three analyses following matching, with mean ages ranging from 58.5 to 64.9 years and mean BMIs ranging from 34.6 to 36.2 kg/m2 among the treatment groups (Table 1). In the primary analysis of any GLP-1 RA use, there was no significant difference in the hazard of appendicitis compared to SGLT2 use (HR 0.99; 95% CI 0.92â1.06), with an absolute risk of 19.9 vs. 17.6 events per 10,000 patients."

Clinical • Diabetes • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

COMPARATIVE EFFICACY OF GLP-1 RECEPTOR AGONISTS, DUAL INCRETIN AGONISTS, AND EMERGING AGENTS IN METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS (UEGW 2026) - "Dual incretin agonists and GLP-1 receptor agonists demonstrate superior efficacy over other pharmacological agents in achieving NASH resolution and fibrosis improvement. These findings provide a comparative hierarchy of emerging therapies and support incretin-based strategies as leading candidates for first-line pharmacologic treatment in MASLD."

Retrospective data • Review • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Pulmonary and Cardiovascular Outcomes With Glucagon-Like Peptide-1 Receptor Agonist Use in Obese Patients With Systemic Sclerosis: A Propensity-Matched Cohort Study (ACR Convergence 2026) - "Adults with SSc and obesity without diabetes were identified... In this propensity-matched real-world cohort of obese, non-diabetic patients with SSc, GLP-1 RA use on or after SSc diagnosis was associated with lower 10-year risks of incident ILD and PH, as well as lower cardiovascular, mortality, renal, and steroid-use outcomes. These findings suggest a potential cardiopulmonary and inflammatory benefit of GLP-1 RAs in SSc and support further validation in studies incorporating granular SSc phenotype, pulmonary function testing, imaging, disease activity, and medication-exposure measures."

Clinical • Acute Kidney Injury • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Hematological Disorders • Immunology • Inflammation • Interstitial Lung Disease • Ischemic stroke • Myocardial Infarction • Nephrology • Obesity • Pulmonary Arterial Hypertension • Pulmonary Disease • Renal Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis • Venous Thromboembolism

Add-on Tirzepatide therapy leads to Improvements in Pain and Clinical Outcomes in Patients with Obesity and Psoriatic Disease and in Patients with Obesity and Non-Inflammatory Arthralgia: Interim Results from a Prospective Cohort Study (ACR Convergence 2026) - No abstract available

Clinical • Clinical data • Genetic Disorders • Immunology • Musculoskeletal Pain • Obesity • Pain

Selective dopamine D5 receptor activation reduces body weight% in diet-induced obese mice (Neuroscience 2026) - "Grant Support NIH Grant R01MH132019; Obesity remains a major health challenge, and neural mechanisms regulating body weight and feeding behavior remain incompletely understood...Although semaglutide and tirzepatide produced greater reductions in body weight than LI-2859, the effects of LI-2859 prompted in-house evaluation of the mixed D1/D5 receptor agonist Tavapadon (0.3 or 1 mg/kg, p.o., b.i.d.) using the same mice and treatment paradigm...Selective D5 receptor activation, though producing significant reductions in weight, does not produce equivalent effects when compared to GLP-1 or GLP-1/GIP agonists while. These findings replicate previous studies showing anorectic effects of D1-like receptor agonists and suggest a specific role for selective D5 activation in DIO models."

Preclinical • CNS Disorders

REAL-WORLD GASTROINTESTINAL, NUTRITIONAL, BILIARY, AND METABOLIC OUTCOMES OF GLP-1-BASED THERAPY IN CHRONIC PANCREATITIS (UEGW 2026) - "In this cohort of CP, exposure to dulaglutide, semaglutide, or tirzepatide was associated with lower risks across multiple outcome domains compared with non-exposed controls."

Clinical • Real-world • Real-world evidence • Acute Kidney Injury • Cardiovascular • Congestive Heart Failure • Gastroenterology • Heart Failure • Myocardial Infarction • Nephrology • Pancreatitis • Renal Disease

Economic evaluations of antiobesity medications: A systematic literature review. (PubMed, Br J Clin Pharmacol) - "We systematically reviewed full economic evaluations of approved antiobesity medications in adults with overweight or obesity, including tirzepatide, semaglutide, liraglutide, naltrexone/bupropion, orlistat, phentermine and phentermine/topiramate. Direct comparative economic evidence between newer agents remains limited. Long-term real-world data and clearer distinctions between cost-effectiveness and affordability are needed to inform policy decisions."

HEOR • Journal • Review • Genetic Disorders • Obesity

Rapid Growth in Medicare Part D Spending on GLP-1 Receptor Agonists Prescribed by Gastroenterologists, 2017â2023 (ACG 2026) - " Using the CMS Medicare Part D Prescriber by Provider and Drug dataset (2017â2023), we extracted all GLP-1 RA claims (dulaglutide, exenatide formulations, liraglutide, semaglutide, tirzepatide) attributed to gastroenterology providers...Because Medicare Part D excludes coverage for anti-obesity medications, observed prescribing likely reflects diabetes- and cardiovascular-related indications and may underestimate future GI demand related to obesity and MASLD management... Medicare Part D spending on GI-prescribed GLP-1 RAs rose 22-fold, from $571,569 in 2017 to $12,665,583 in 2023; 30-day fills grew 14.7-fold (876 to 12,862). Semaglutide accounted for most spending growth, increasing from $126,162 (169 fills) in 2019 to $8,798,765 (9,098 fills) in 2023 and comprising 69% of 2023 GLP-1 spending. Tirzepatide grew from $70,856 in 2022 to $1,942,314 in 2023."

Medicare • Reimbursement • US reimbursement • Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

Comparative Efficacy and Safety of FGF21 Analogues in MASH: Which Agents Are Advancing and Why? (ACG 2026) - "Introduction: Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of progressive liver fibrosis and cirrhosis... A structured literature review of PubMed/MEDLINE was conducted through April 2026 using keywords and MeSH terms including âMASH,â âNASH,â âfibroblast growth factor 21,â âFGF21 analogues,â âefruxifermin,â âpegozafermin,â âefimosfermin,â âpegbelfermin,â âresmetirom,â âsemaglutide,â âtirzepatide,â âsurvodutide,â âlanifibranor,â and âclinical trial.â Included studies were randomized controlled trials in biopsy-confirmed MASH or MASLD reporting histologic data...Trials of pegbelfermin and MK-3655 did not meet primary endpoints... Twelve trials (N=3,640) were included. Among FGF21 analogues, efruxifermin 50 mg showed the greatest response, with fibrosis improvement up to 75% and MASH resolution up to 62%..."

Clinical • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF21

GLP-1-based treatments and long-term clinical outcomes in MASLD amongst older adults: a retrospective cohort study. (PubMed, Age Ageing) - "In older adults with MASLD, GLP-1 RA initiation was linked to lower risks of hepatic decompensation, hospitalisation and mortality, with higher rates of selected adverse events."

Clinical data • Journal • Retrospective data • Cardiovascular • Geriatric Disorders • Hepatology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Pancreatitis • Retinal Disorders • Rheumatology • Sarcopenia • Transplantation