Mounjaro (tirzepatide) / Eli Lilly - LARVOL DELTA

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

Comparative Metabolic Effects of Semaglutide, Tirzepatide, and Retatrutide in a Monogenic (db/db) Mouse Model of Obesity (ADA 2025) - "Overall, Tirzepatide demonstrated the most pronounced metabolic benefits in the monogenic model of obesity coupled with type-2 diabetes."

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

Antiobesity medications in adult and pediatric obesity and metabolic dysfunction-associated steatotic liver disease. (PubMed, Pharmacol Rev) - "The most effective antiobesity drugs evaluated in double-blind, randomized controlled trials include semaglutide, tirzepatide, and retatrutide with up to 10.8%, 17.8%, and 22.1% placebo-subtracted bodyweight loss, respectively, in adults after 48-72 weeks. SIGNIFICANCE STATEMENT: This work reviews the current antiobesity medications, their structure, mode of action, and effectiveness. These medications are revolutionizing the management of metabolic dysfunction-associated steatotic liver disease by significantly reducing hepatic steatosis, disease activity, and even liver fibrosis."

Journal • Review • Fibrosis • Genetic Disorders • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Pediatrics

MWN109—A Novel Fatty Acid–Modified GLP-1/GIP/GCG Triagonist for Dual-Format Weight Management Demonstrates Superior Efficacy in Nonhuman Primates (ADA 2025) - "This study evaluates its weight loss efficacy, pharmacokinetics, and safety in NHP. In diet-induced obesity (DIO) monkey studies, SC MWN109 was compared with tirzepatide and retatrutide. MWN109 exhibits greater weight loss efficacy, favorable pharmacokinetics, and a promising safety profile, supporting its potential as a next-generation obesity treatment. The SC formulation has received IND clearance from both the NMPA and FDA and is currently in Phase 1 trials."

Clinical • Late-breaking abstract • Metabolic Disorders • Obesity • GCG

Robust Antiobesity Effect and Mechanistic Insights of HM15275, a Novel Long-Acting GLP-1/GIP/Glucagon Triple Agonist in Animal Model of Obesity (ADA 2025) - "Tirzepatide (TZP) and retatrutide (RETA, in-house synthesis) served as comparative controls. In DIO mice, HM15275 treatment for 3 weeks resulted in a greater weight loss (-39.9% vs. D0) than TZP (-25.3% vs. D0). In conclusion, HM15275 demonstrates potent weight loss with improved weight loss quality in DIO mice. Also, comprehensive elucidation of the underlying mechanism of action has been demonstrated. Clinical translation of such findings is under investigation in an ongoing phase 1, 4-week multiple ascending dose (MAD) study in obese patients."

Preclinical • Metabolic Disorders • Obesity

Evaluating Thyroid Cancer Risk in Glucagon-like Peptide-1 Analog Users With Thyroid Nodules. (PubMed, J Surg Res) - "Our study indicates a relatively low incidence of thyroid cancer among patients with thyroid nodules treated with GLP-1 analogues."

Journal • Endocrine Cancer • Oncology • Pediatrics • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma

A Study of Tirzepatide (LY3298176) Once Weekly in Adolescent Participants Who Have Obesity or Overweight With Weight-Related Comorbidities (clinicaltrials.gov) - P3 | N=150 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2026 ➔ Jul 2029 | Trial primary completion date: Oct 2026 ➔ May 2026

Enrollment closed • Trial completion date • Trial primary completion date • Genetic Disorders • Obesity

GLOW: GLP-1s to Enhance Lasting Optimal Weight (clinicaltrials.gov) - P4 | N=40 | Recruiting | Sponsor: Wake Forest University Health Sciences | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

A Study of Bimagrumab (LY3985863) and Tirzepatide (LY3298176), Alone or in Combination, in Participants With Obesity or Overweight With Type 2 Diabetes (clinicaltrials.gov) - P2 | N=180 | Active, not recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Active, not recruiting

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

Lilly to launch Mounjaro pen in India to compete with Novo’s Wegovy (MSN News) - "Eli Lilly said on Thursday India's drug regulator had approved the launch of pre-filled injector pens of its blockbuster weight-loss drug, Mounjaro, giving it more options to compete with Novo Nordisk's recently launched Wegovy....Mounjaro KwikPen, for once-weekly use, has been approved by the Central Drugs Standard Control Organization for six dose strengths of 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg and 15 mg, the company said in a statement."

Approval • Obesity

Bimagrumab Augments Metabolic Rate to Improve Incretin-Induced Weight Loss in Obese Mice (ADA 2025) - "Hence, targeting the myostatin/activin pathway may provide a greater magnitude and quality weight loss in the management of excess adiposity. The primary objective of the current investigation was to determine whether the ACVR2A/B antagonist mAb bimagrumab provides a greater quality of weight loss when dosed in combination with incretin based multi-receptor agonists in obese mice. A major finding of our studies is that treatment with bimagrumab enhanced GLP-1R agonist and tirzepatide induced weight loss in animals housed at thermoneutrality, while there was no effect of a neutralizing mAb targeting myostatin. Collectively, our findings provide further support to the notion that inhibition of the myostatin/activin pathway in adipose tissue may promote a greater quality of weight loss in the management of excess adiposity."

Late-breaking abstract • Preclinical • Metabolic Disorders • Obesity • ACVR2A • TGFB1

Cirius Therapeutics Announces Positive Data for MPC Inhibitor 0602K Alone and in Combination with Tirzepatide (PRNewswire) - "Detailed data is being presented as a late-breaking poster at the American Diabetes Association's (ADA) 85th Scientific Sessions....Both 0602K+tirzepatide and tirzepatide alone produced very similar rapid and substantial weight loss through as long as 6 weeks treatment. 0602K + tirzepatide reduced the loss of lean mass and muscle typically seen with tirzepatide alone.....Separately, collaborators at the University of Texas Health Science Center at San Antonio conducted a small (n=3) pilot mechanistic clinical study of 0602K effects on muscle composition and metabolic function. In patients with obesity & T2D. assessed at baseline and after taking 250mg 0602K daily for 3 months: 0602K decreased intramyocellular lipid (fat inside muscle cells) by ~50%; Increased muscle metabolic function (insulin-mediated glucose disposal) by ~50%; Reduced HbA1c from an average of 8.33% at baseline to 6.97%."

Clinical data • Preclinical • Obesity • Type 2 Diabetes Mellitus

MPC-Directed Insulin Sensitizer MSDC-0602K Combines with Tirzepatide to Maintain Muscle Mass/Function and Restructure Adipose Tissue (ADA 2025) - "Metabolic reprogramming with 0602K may extend the benefits of weight loss with GLP1 receptor agonists through effects in multiple tissues including muscle and adipose."

Late-breaking abstract • Metabolic Disorders • Obesity

Tirzepatide gains US Food and Drug Administration approval for the management of obstructive sleep apnea: Implications for oral health care providers. (PubMed, J Am Dent Assoc) - "Tirzepatide offers a novel approach to managing OSA by means of targeting metabolic and inflammatory factors that contribute to this condition. It has the potential to affect oral health, including the management of periodontal disease, dental implant procedures, and orthodontic interventions. Dental care providers should consider patient-centered needs and the interrelationship between systemic health and oral health."

FDA event • Journal • Review • Cardiovascular • Dental Disorders • Genetic Disorders • Heart Failure • Hypertension • Obesity • Obstructive Sleep Apnea • Periodontitis • Respiratory Diseases • Sleep Apnea • Sleep Disorder

Tirzepatide in Obesity-Related Heart Failure With Preserved EF: Weight Loss and Structural Adaptations. (PubMed, J Am Coll Cardiol) - No abstract available

Journal • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Obesity

Reply: Tirzepatide in Obesity-Related Heart Failure With Preserved EF: Weight Loss and Structural Adaptations. (PubMed, J Am Coll Cardiol) - No abstract available

Journal • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Obesity

Tirzepatide for Obesity Treatment and Diabetes Prevention. Reply. (PubMed, N Engl J Med) - No abstract available

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity

Tirzepatide for Obesity Treatment and Diabetes Prevention. (PubMed, N Engl J Med) - No abstract available

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity

Tirzepatide for Obesity Treatment and Diabetes Prevention. (PubMed, N Engl J Med) - No abstract available

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity

Efficacy and safety of tirzepatide for weight loss in patients with obesity or type 2 diabetes: a systematic review and meta-analysis (Frontiers) - "Tirzepatide induced a mean weight reduction of -10.39 kg versus placebo (95% CI: -10.80 to -9.99; p < 0.00001). Subgroup analyses by diabetes status showed that patients with type 2 diabetes lost -6.17 kg (95% CI: -7.16 to -5.17; p < 0.00001) at 5 mg, -8.57 kg (95% CI: -9.41 to -7.74; p < 0.00001) at 10 mg, and -9.60 kg (95% CI:-10.32 to -8.89; p < 0.00001) at 15 mg. Non-diabetic participants experienced greater absolute losses of -12.10 kg (95% CI: -13.47 to -10.72; p < 0.00001), -15.94 kg (95% CI: -17.25 to -14.62; p < 0.00001), and -17.86 kg (95% CI: -19.19 to -16.54; p < 0.00001) at the respective doses....Tirzepatide induces significant, dose-dependent weight loss, with higher doses yielding greater reductions. While gastrointestinal side effects were common, they were generally mild to moderate and did not increase serious adverse events."

Review • Obesity • Type 2 Diabetes Mellitus

A Pharmacometric Method for Quantitative Determination of Improvement in Body Composition and Characterization of the Exposure-Response Relationship during Treatment of Obesity with Tirzepatide. (PubMed, Clin Pharmacol Ther) - "We present and propose the use of a pharmacometric-based body composition model to describe weight reduction in future clinical trials investigating similar drugs in similar patient populations, in lieu of DXA scans. In such future trials, our approach can be used to describe exposure-response relationships, optimize doses, and investigate covariates, while considering potential differences in fat mass and FFM."

Journal • Genetic Disorders • Obesity

GLP-1-based therapeutics for cardiorenal protection in metabolic diseases. (PubMed, Nephrol Dial Transplant) - "An example is tirzepatide, a dual GLP-1/GIP receptor agonist, which has been approved for both T2D and obesity-management, demonstrating up to 22.5% weight-loss in phase-3 trials. This review explores the landscape of current and emerging GLP-1-based therapies, their efficacy in managing hyperglycemia and bodyweight, recent evidence supporting their cardiorenal benefits, and clinical implications of these advancements."

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

The need to address the risk of osteosarcopenia induced by tirzepatide therapy. (PubMed, Clin Exp Rheumatol) - No abstract available

Journal

Systemic Inflammatory Response Syndrome Following High-Dose Intravenous Glutathione-Containing Revitalising Solution in a Patient on Tirzepatide: A Case Report. (PubMed, Cureus) - "This case highlights the dangers of cosmetic intravenous therapies administered in non-clinical settings and underscores the need for thorough medication and supplement histories in acute presentations. Clinicians should maintain heightened suspicion for such products in unexplained systemic inflammation and advocate for stricter regulatory oversight to mitigate risks."

Journal • Hematological Disorders • Hepatology • Immunology • Inflammation • Liver Failure • Systemic Inflammatory Response Syndrome • CRP

Product Theaters - Mounjaro® (tirzepatide) Product Theater (ADA 2025) - "It is being presented consistent with FDA guidelines and is not approved for continuing education credit. (*) Continuing Education Credit Is Not Awarded for this Session."

Metabolic Disorders