cagrilintide (AM833) / Novo Nordisk - LARVOL DELTA

RAMBO: The Role of the Amylin Analogue Cagrilintide in Bone Metabolism (clinicaltrials.gov) - P1 | N=144 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

CagriSema drives weight loss in rats by reducing energy intake and preserving energy expenditure. (PubMed, Nat Metab) - "CagriSema is a combination of amylin (cagrilintide) and glucagon-like peptide-1 (semaglutide) analogues being developed for weight management...By contrast, pair-feeding causes less-pronounced weight loss, while weight matching requires a 51% decrease in food intake. Therefore, approximately one-third of CagriSema's weight loss efficacy arises from an effect on energy expenditure, the blunting of metabolic adaptation, which contributes to the successful treatment of obesity."

Journal • Preclinical • Genetic Disorders • Obesity

Characterization of 0839 - A tool compound for pre-clinical mode-of-action studies of amylin analogues such as cagrilintide. (PubMed, Life Sci) - "Both compounds mainly reduced body weight by fat mass reduction and equally improved metabolic parameters. Notably, 0839 is available through Novo Nordisk Compound Sharing, enabling advancement of mode-of-action studies in mice and rats whilst usage of cagrilintide and other amylin analogues in clinical development and restricted due to pharmacovigilance rules."

Journal • Preclinical • Diabetes • Genetic Disorders • Metabolic Disorders • Type 2 Diabetes Mellitus

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

Beneficial effects of the combinatory theraphy with sub-maximal doses of cagrilintide and tirzepatide on body weight loss in obese rats (EASD 2025) - "Combination therapy at sub-maximal doses of cagrilintide and tirzepatide elicited significantly greater weight loss, higher reduction in food intake and improved metabolic profile compared to monotherapy, suggesting the potential opportunity of this combination for further clinical development."

Preclinical • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

REDEFINE1: a randomised study of combined semaglutide 2.4 mg and cagrilintide 2.4 mg for the treatment of overweight or obesity in adults (EASD 2025) - P3 | "CagriSema provided robust and clinically meaningful weight reduction in adults with overweight and obesity, superior to sema or cagri alone, with a well-tolerated safety profile consistent with other incretin-based therapies."

Clinical • Metabolic Disorders • Obesity

REDEFINE 2: a randomised trial of combined semaglutide 2.4 mg and cagrilintide 2.4 mg for the treatment of adults with BMI ≥27kg/m2 and type 2 diabetes (EASD 2025) - P3 | "Clinical Trial Registration Number: NCT05394519 Background and aims: Semaglutide and cagrilintide monotherapies have been shown to induce weight loss... CagriSema provided clinically meaningful weight reduction and improvements in metabolic health in adults with BMI ≥27 kg/m2 and T2D, with tolerability comparable to other incretin-based therapies."

Clinical • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3. (PubMed, EBioMedicine) - "Altogether, these results demonstrate the dependency of cagrilintide on AMY1R and AMY3R to lower body weight."

Journal • Genetic Disorders • Obesity

A Study of How CagriSema Works on Appetite in People With Excess Body Weight (clinicaltrials.gov) - P1 | N=164 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Trial primary completion date: Dec 2025 ➔ Apr 2025

Trial primary completion date • Genetic Disorders • Obesity

Eloralintide (LY3841136), a selective amylin analog, lowered body weight with improved quality of weight loss and GI tolerability in rats compared to cagrilintide (EASD 2025) - "Eloralintide demonstrated preclinical improvements in efficacy, GI tolerability, and quality of weight loss compared to the non-selective amylin analog cagrilintide. These findings support clinical investigation of eloralintide as a weight loss therapeutic."

Preclinical • Metabolic Disorders

Mechanisms for the preservation of energy expenditure during CagriSema-induced weight loss in obese rats (EASD 2025) - "Here, we studied molecular mechanisms involved in the prevention of metabolic adaptation during CagriSema-induced weight loss.Materials and Diet-induced obese rats were treated with vehicle or CagriSema (cagrilintide: 2 nmol/kg and semaglutide: 2 nmol/kg) for 20 days... Taken together, we conclude that CagriSema treatment prevents metabolic adaptation partly by preventing a reduction in mitochondrial proton leak in skeletal muscle. In addition, the multi-omics signature indicates that CagriSema-induced weight loss, in contrast to weight loss by diet restriction, bypasses the normal molecular adaptations to weight loss in metabolically active tissues. Human trials are required to determine the translatability and clinical relevance of these findings."

Preclinical • Diabetes • Metabolic Disorders • Obesity

MET-233 is a differentiated efficacious amylin analogue in preclinical studies, combinable with MET-097, an ultra-long acting GLP-1 receptor agonist (EASD 2025) - "Here, we profile MET-233, comparing it to other clinical-stage amylin analogues, cagrilintide, GUB014295, and petrelintide, and present data supporting the development of MET-233 and MET-097 as a combination therapeutic.Materials and Compounds were characterised in vitro via cAMP accumulation assays at human and rat calcitonin receptors (hCTR/rCTR) and human amylin receptor 3 (hAMYR3). In preclinical models, MET-233 is differentiated by its potency (efficacy at very low doses), PK durability, and combinability with MET-097, a fully-biased ULA GLP-1RA. Taken together, these properties suggest the potential for MET-233 to be combined with MET-097 as a differentiated, ULA treatment option for obesity and related diseases."

Preclinical • Metabolic Disorders • Obesity

Eloralintide, a selective, long-acting amylin receptor agonist for obesity: phase 1 proof of concept (EASD 2025) - P1 | "Unlike other amylin agonist molecules (e.g., Cagrilintide), it is designed to have minimal calcitonin activity in the clinic.Materials and This 12 week (wk) phase 1, randomized, placebo-controlled, double-blind study evaluated safety, tolerability, PK, and PD of QW subcutaneous Elora in participants with obesity or overweight. At 12 wks, Elora QW was well tolerated with minimal GI AEs and resulted in meaningful weight loss. An ongoing Phase 2 study will further explore efficacy and tolerability of Elora."

P1 data • Metabolic Disorders • Obesity

MET-233 Is an Ultra-Long-Acting Amylin Receptor Agonist (ADA 2025) - "The pharmacokinetics of MET-233 and cagrilintide were compared after single administration in pigs... The long half-life of MET-233 observed in pigs suggests that infrequent administration in humans may be achievable. Results from chronic administration to rats indicate that MET-233 is highly effective, and additive impact on body weight was observed when coadministered with MET-097. The potency, durability, and combinability of MET-233 and MET-097 highlight the potential of MET-233 as a differentiated treatment option."

Metabolic Disorders • Obesity

BGM1812, a Novel Amylin Analog, Enhances Receptor Agonism and Induces Superior Weight Loss in Preclinical Models (ADA 2025) - "Introduction and Objective: Amylin receptor agonists (e.g. petrelintide and cagrilintide) have shown promise for weight management...This study evaluates BGM1812's pharmacological properties, weight loss efficacy, and potential synergy with a GLP-1/GIP dual agonist (BGM0504) in diet-induced obese (DIO) rats. Receptor activation: cAMP assays measured EC50 for amylin and calcitonin receptor activation... BGM1812 demonstrates superior receptor activation, robust weight loss effects, and synergistic potential with GLP-1/GIP dual agonism, supporting its development as a next-generation amylin analog for obesity treatment."

Late-breaking abstract • Preclinical • Metabolic Disorders • Obesity

Novel Oral Small Molecule ACCG-2671—A Dual Amylin and Calcitonin Receptor Agonist Development Candidate for Obesity Therapy (ADA 2025) - "Cagrilintide, a long-acting dual amylin and calcitonin receptor agonist (DACRA) peptide, has demonstrated promising efficacy and safety profile in clinical trials, but an oral small molecule DACRA with good bioavailability and stability could provide a more convenient and accessible alternative for obesity treatment. ACCG-2671 is a novel oral small molecule DACRA that significantly reduces body weight in obese rats. Its pharmacological profile and preclinical efficacy support its advancement as a development candidate, alone and in combination for obesity treatment, potentially offering a novel, convenient, and accessible therapeutic option."

Late-breaking abstract • Metabolic Disorders • Obesity

Effect of Combined Therapy with Once-Weekly Subcutaneous Cagrilintide 2.4 mg and Semaglutide 2.4 mg (CagriSema) on Energy Intake, Gastric Emptying, and Appetite in Adults with Overweight or Obesity (ADA 2025) - P1 | "CagriSema contributes to weight management in adults with overweight or obesity by significantly reducing energy intake and appetite without delaying GE."

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

Cagrisema-Induced Weight Loss in Diet-Induced Obese Rats Relies on Preserved Mitochondrial Leak Respiration in Skeletal Muscle (ADA 2025) - "In rats, CagriSema (CS), a combination of semaglutide (a GLP-1 analogue) and cagrilintide (an amylin analogue), prevents metabolic adaptation, but the mechanisms behind this effect are unknown.Objective: To investigate the effects of CS on metabolic efficiency in two of the most energy consuming organs - liver and skeletal muscle. Diet-induced obese male rats were subjected to vehicle or CS treatment (2+2 nmol/kg of semaglutide and cagrilintide) for 20 days (n=13). CS prevents metabolic adaptation to weight loss partly by preventing a reduction in mitochondrial leak respiration in skeletal muscle. Omics profiles and other functional mechanisms are currently under investigation."

Preclinical • Metabolic Disorders • Obesity

Eloralintide, a Selective, Long-Acting Amylin Receptor Agonist for Obesity—Phase 1 Proof of Concept (ADA 2025) - P2 | "Unlike other amylin agonist molecules (e.g. Cagrilintide), it is designed to have minimal calcitonin activity in the clinic. The 12 wk phase 1, randomized, placebo (PBO) controlled, double blind study evaluated safety, tolerability, PK, and PD of QW SC Elora in participants with obesity or overweight. At 12 wks, Elora QW was well tolerated with minimal GI AEs and resulted in meaningful weight loss. A phase 2 study (NCT06230523) will further explore safety and efficacy of Elora."

P1 data • Metabolic Disorders • Obesity

Eloralintide (LY3841136), a Selective Amylin Mimetic, Lowered Body Weight with Improved Quality of Weight Loss and GI Tolerability in Rats Compared with Cagrilintide (ADA 2025) - "Eloralintide demonstrated preclinical improvements in efficacy, GI tolerability, and quality of weight loss compared to the non-selective amylin analog cagrilintide. These findings support clinical investigation of eloralintide as a weight loss therapeutic."

Preclinical • Metabolic Disorders

The Amylin Receptor Selective Agonist NN1213 Reduces Food Intake and Body Weight in Rats without Decreasing Calcium Plasma Levels (ADA 2025) - "Cagrilintide and eloralintide are both AMYR and CTR agonists whereas NN1213 is a selective AMYRs agonist that also decreases body weight in rats."

Preclinical • Metabolic Disorders • Obesity

Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. (PubMed, N Engl J Med) - P3 | "Cagrilintide-semaglutide provided significant and clinically relevant body-weight reductions in adults with overweight or obesity, as compared with placebo. (Funded by Novo Nordisk; REDEFINE 1 ClinicalTrials.gov number, NCT05567796.)."

Journal • Cardiovascular • Constipation • Diabetes • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Metabolic Disorders • Obesity • Pain

Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. (PubMed, N Engl J Med) - P3 | "Once-weekly cagrilintide-semaglutide (at a dose of 2.4 mg each) resulted in a significantly lower body weight than placebo in adults with obesity and type 2 diabetes. (Funded by Novo Nordisk; REDEFINE 2 ClinicalTrials.gov number, NCT05394519.)."

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

A Research Study to Look at How Well CagriSema Helps People Living With Obesity Lose Weight and Maintain Weight Loss in the Long-term (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

A Research Study to Look at How Well CagriSema Helps People Living With Obesity Lose Weight and Maintain Weight Loss in the Long-term (clinicaltrials.gov) - P3 | N=600 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P3 trial • Genetic Disorders • Obesity