retatrutide (LY3437943) / Eli Lilly - LARVOL DELTA

Approved and Emerging Hormone-Based Anti-Obesity Medications: A Review Article. (PubMed, Indian J Endocrinol Metab) - "Two GLP1RAs, namely Liraglutide and Semaglutide, have been approved by the Food and Drug Administration (FDA) and European Medicine Agency (EMA) for use in clinical practice for weight loss. Three oral GLP1RAs, namely Semaglutide, Danuglipron, and Orforglipron, are undergoing advanced clinical trials in individuals with obesity. Amylin receptor agonist (AMYRA) Cagrilintide, when used alone or in combination with Semaglutide, has demonstrated substantial weight reduction in clinical trials. Tirzepatide, a dual agonist for the glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors, has been observed to be associated with a significant placebo-subtracted weight reduction of 17.8% in a 72-week randomized controlled trial...Three long-acting GLP1R/glucagon receptor (GCGR) dual agonists, namely Survodutide, Mazdutide, and Pemvidutide, exhibited significant weight loss in clinical trials. Retatrutide, a GLP1R/GCGR/GIPR tri-agonist, has been associated with a..."

Journal • Review • Cardiovascular • Genetic Disorders • Obesity

The impact of weight loss on fat-free mass, muscle, bone and hematopoiesis health: Implications for emerging pharmacotherapies aiming at fat reduction and lean mass preservation. (PubMed, Metabolism) - "Novel compounds in the pipeline, such as Bimagrumab, Trevogrumab, and Garetosmab-which inhibit activins and myostatin signaling-have demonstrated promise in preventing muscle loss while promoting fat loss...Since this dual therapeutic approach could help address the challenges of muscle and bone loss during weight loss, well-designed studies are needed to optimize these strategies and assess long-term benefits. For the time being, considerations like advanced age and prefrailty may affect the choice of suitable candidates in clinical practice for current and emerging anti-obesity medications due to the associated risk of sarcopenia."

Journal • Review • Cardiovascular • Diabetes • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Obesity • Osteoporosis • Sarcopenia

Pharmacotherapy of Obesity (ESPE 2024) - "The MC4 receptor agonist, setmelanotide has also been approved for the treatment of some very rare genetic causes of obesity, specifically POMC deficiency, leptin receptor deficiency and Bardet-Beidl Syndrome; with these targeted therapies weight loss of 15% or more is to be expected and will become the treatment standard. In the future we may see even greater weight loss, as GLP1 RAs are combined with other gut hormone analogues; a combination drug that targets both GLP1 and GIP, tirzepatide, is already approved for treatment of adults with obesity; paediatric trials are ongoing. Others, such as the amylin analogue cagrilintide, and triple agonists that target GLP1, GIP and glucagon, such as retatrutide, are also looking promising. Currently, these effective treatments are given by daily or weekly injection, but recent data has shown that higher doses of semaglutide are effective when given orally together with an absorption enhancer, and several small molecule oral..."

Cardiovascular • Genetic Disorders • Obesity • Pediatrics • POMC-null Obesity • LEP • LEPR

TRIUMPH-5: A Study of Retatrutide (LY3437943) Compared to Tirzepatide (LY3298176) in Adults Who Have Obesity (clinicaltrials.gov) - P3 | N=800 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

The power of three: Retatrutide's role in modern obesity and diabetes therapy. (PubMed, Eur J Pharmacol) - "As a transformative therapeutic modality, retatrutide represents a beacon of hope, signifying transformative changes in the management landscape of obesity and type 2 diabetes mellitus (T2DM), and warranting continued exploration and refinement in clinical practice. This narrative review examines the therapeutic potential of retatrutide in the management of obesity and T2DM."

Journal • Review • Cardiovascular • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Pediatrics • Type 2 Diabetes Mellitus

The "Weight" for a New Agent Is Almost Over: A Commentary on the Novel Triagonist Retatrutide for Obesity. (PubMed, J Pharm Technol) - "The most common adverse effects were gastrointestinal. Ongoing phase II and III studies aim to further evaluate the safety and efficacy of retatrutide as a novel triagonist for obesity treatment."

Journal • Gastrointestinal Disorder • Genetic Disorders • Obesity

TRIUMPH-2: A Study of Retatrutide (LY3437943) in Participants With Type 2 Diabetes Mellitus Who Have Obesity or Overweight (clinicaltrials.gov) - P3 | N=1000 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder • Type 2 Diabetes Mellitus

Development of the Eating Behavior and Appetite Questionnaire (EBAQ) (OBESITY WEEK 2024) - " Concept elicitation interviews were conducted with 40 adults with obesity upon exit of a phase 2 clinical trial for retatrutide... The newly developed EBAQ may provide an important means of capturing evidence of the impact of AOMs on aspects of eating behavior and appetite in adults with obesity that cannot be collected using existing PRO measures. The content validity of the EBAQ will be further examined in future research."

Genetic Disorders • Obesity

Weight and Emotions Scale (WES): Assessing the Emotional Impact of Obesity (OBESITY WEEK 2024) - P2 | " The WES was developed based on data from a literature review (6 disease-specific and 2 general health status PROMs), interviews with participants from a phase 2 trial for retatrutide (NCT04881760), and interviews with obesity medicine specialists... The WES may be useful in clinical trials and observational research to assess the emotional impact of obesity and benefits of obesity treatment. Findings support the initial content validity of the WES as patients and clinicians considered the concepts measured to be relevant."

Genetic Disorders • Obesity

Sex Differences in Body Weight Reduction Achieved With Incretin-Based Therapies: A Meta-Analysis (OBESITY WEEK 2024) - "The following studies were included in the analysis: AWARD-1, -2, -5, -6, -8, -11 (dulaglutide type 2 diabetes studies), SURPASS-1, -2, -3 (tirzepatide type 2 diabetes studies) and SURMOUNT-1, -2, -3, -4 (tirzepatide obesity studies), STEP 1 (semaglutide obesity study), and 2 phase 2 studies of retatrutide (1 type 2 diabetes study and 1 obesity study). Data from active comparators in these trials (sitagliptin, liraglutide, insulin glargine and insulin degludec) were included in the analysis... Women exhibit statistically significantly greater weight reduction than men in trials of incretin-based therapies. In addition, the results suggest that sex differences in weight reduction are greater with incretin-based therapies that induce greater weight reduction in women. The mechanisms underlying this sex difference require further investigation."

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

Evaluating the Impact of Novel Incretin Therapies on Cardiovascular Outcomes in Type 2 Diabetes: An Early Systematic Review. (PubMed, Pharmaceuticals (Basel)) - "Background This systematic review is registered with CRD42024507397 protocol number and aims to compare the known data about retatrutide on long-term cardiovascular (CV) protection with tirzepatide, an incretin with recent proven CV benefits. Results The seven included studies were assessed for bias with the Newcastle Ottawa scale, heterogenous, and emphasized the potential CV beneficial effect of type 2 DM (T2DM) therapies (glycemia, glycated A1c hemoglobin, body weight, lipid profile, blood pressure and renal parameter). Discussions Further, longer follow-up studies are necessary to verify the long-term CV protection, standardize the specific aspects of CV risk, and compare with subjects without T2DM for a more integrative interpretation of the CV effects independent of the improvement of metabolic activity."

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

Eating Behaviors in Obesity: Identifying Important Concepts and Developing a Conceptual Framework (OBESITY WEEK 2024) - "In addition to the TLR results, findings from phase 2 clinical trial exit interviews of retatrutide, interviews with clinical experts in obesity, and input from PRO experts informed development and refinement of a CF for eating behavior... The eating behavior conceptual framework can serve as a guide to develop a robust PRO measure which appropriately captures eating behavior concepts relevant to patients with obesity."

Genetic Disorders • Obesity

Improved HRQoL and Eating Behaviors in Adults With Obesity Treated With Retatrutide: A Phase 2 Study (OBESITY WEEK 2024) - "In adults with obesity or overweight, RETA treatment significantly improved multiple domains of HRQoL, reduced disinhibition, and reduced hunger more than PBO in this Phase 2 study."

Clinical • P2 data • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Pain • Type 2 Diabetes Mellitus

TRIUMPH-5: A Study of Retatrutide (LY3437943) Compared to Tirzepatide (LY3298176) in Adults Who Have Obesity (clinicaltrials.gov) - P3 | N=800 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P3 trial • Genetic Disorders • Obesity

Perceived Benefits of Retatrutide for Obesity: A Qualitative Study of Phase 2 Trial Participants (OBESITY WEEK 2024) - P2 | "Most participants treated with retatrutide reported achieving weight loss goals, as well as improvements in appetite and eating behaviors, emotions, and overall lifestyle."

P2 data • Diabetes • Genetic Disorders • Obesity

ACCURATE PREDICTION OF LIVER FAT REDUCTIONS ACROSS RANGE OF WEIGHT LOSS BY QUANTITATIVE SYSTEMS PHARMACOLOGY MODELING (AASLD 2024) - "The overall effects of WL on steatosis reductions in NAFLDsym were calibrated with data from clinical studies with liraglutide (1), canagliflozin (2), and retatrutide (3). WL in excess of 10% has substantial, positive effects on reducing hepatic lipid burden and steatosis."

Metabolic Dysfunction-Associated Steatohepatitis

Retatrutide. (PubMed, Clin Diabetes) - No abstract available

Journal

RETATRUTIDE IMPROVES STEATOHEPATITIS IN A NEW ACCELERATED MOUSE MODEL OF DIET-INDUCED STEATOHEPATITIS WITH A FRUCTOSE BINGE (AASLD 2024) - "Female mice are more prone to acute fructose-induced liver injury than males, whereas both female and male mice develop robust steatohepatitis in a novel chronic diet-induced steatohepatitis model over 31 days with a final fructose binge. Retatrutide improves diet-induced steatohepatitis in mice."

Preclinical • Genetic Disorders • Hepatology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

TRIUMPH-3: A Study of Retatrutide (LY3437943) in Participants With Obesity and Cardiovascular Disease (clinicaltrials.gov) - P3 | N=1800 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Genetic Disorders • Obesity

Modern Challenges in Type 2 Diabetes: Balancing New Medications with Multifactorial Care. (PubMed, Biomedicines) - "A key focus of this review is tirzepatide, a dual agonist of the glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors...We also address future perspectives in diabetes management, including the potential of retatrutide as a triple receptor agonist and evolving guidelines advocating for a comprehensive, multifactorial approach to care...By focusing on the physiological mechanisms of these new therapies, this review underscores their role in enhancing T2DM management and highlights the importance of personalized care plans to address the complexities of the disease. This holistic perspective aims to improve patient quality of life and long-term health outcomes."

Journal • Review • Diabetes • Metabolic Disorders • Tobacco Cessation • Type 2 Diabetes Mellitus

A Study of LY3437943 in Healthy Participants With a High Body Mass Index (clinicaltrials.gov) - P1 | N=85 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Trial completion • Obesity

TRIUMPH-1: A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight (clinicaltrials.gov) - P3 | N=2100 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Genetic Disorders • Immunology • Metabolic Disorders • Musculoskeletal Pain • Obesity • Obstructive Sleep Apnea • Osteoarthritis • Pain • Respiratory Diseases • Rheumatology • Sleep Disorder • Type 2 Diabetes Mellitus

Effects of once-weekly subcutaneous retatrutide on weight and metabolic markers: A systematic review and meta-analysis of randomized controlled trials. (PubMed, Metabol Open) - "In this meta-analysis, the use of once-weekly subcutaneous retatrutide was associated with a significant reduction in body weight and improvement of metabolic markers in patients with overweight, obesity and/or T2D, compared with placebo, with an increase in non-severe gastrointestinal and hypersensitivity adverse events. Phase 3 RCTs are expected to shed further light on the efficacy and safety of once-weekly subcutaneous retatrutide over the long term."

Clinical • Journal • Retrospective data • Review • Diabetes • Gastrointestinal Disorder • Genetic Disorders • Immunology • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Seven glucagon-like peptide-1 receptor agonists and polyagonists for weight loss in patients with obesity or overweight: an updated systematic review and network meta-analysis of randomized controlled trials. (PubMed, Metabolism) - "Retatrutide (both doses) and tirzepatide exhibited superior efficacy compared to other GLP-1 receptor agonists and polyagonists in reducing body weight and waist circumference. Patients without T2DM, those with a high BMI, and individuals undergoing longer treatment cycles demonstrated significantly greater weight loss and reductions in waist circumference. Dual or triple receptor agonists (GLP-1 plus glucose-dependent insulinotropic polypeptide and/or Glucagon receptor) are more effective for weight loss than GLP-1 receptor agonists."

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

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, TG103), GLP-1 RA/amylin agonist (CagriSema), GLP-1/glucagon RAs (mazdutide, 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 • Developmental Disorders • Genetic Disorders • Obesity