cagrilintide (AM833) / Novo Nordisk - LARVOL DELTA

Diabetes Mellitus and Chronic Kidney Disease: The Future Is Being Surpassed. (PubMed, J Clin Med) - "(5) The mineralocorticoid receptor antagonist (MRA) finerenone has been tested in RCTs as a kidney protective agent...Many novel agents-many of them proven not only for DM management but also for the treatment of obesity with or without DM or heart failure (HF)-are now in development and may be added to the five classical pillars: other non-steroidal MRA (balcinrenone); aldosterone synthase inhibitors (baxdrostat and vicadrostat); other GLP-1 RA (tirzepatide, survodutide, retatrutide, and cagrilintide); ET1 R antagonists, (zibotentan); and soluble guanylate cyclase activators (avenciguat). These new agents aim to slow disease progression further and reduce cardiovascular risk. Future strategies rely on integrated, patient-centered approaches and personalized therapy to curb renal disease and its related complications."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Diabetic Nephropathy • Genetic Disorders • Heart Failure • Metabolic Disorders • Nephrology • Obesity • Renal Disease

Amylin receptors as therapeutic targets in obesity: Emerging peptide-based strategies. (PubMed, Vascul Pharmacol) - "The article is a review of the emerging preclinical and clinical data regarding the application of peptide-based amylin receptor agonists (AMYRAs), including pramlintide and cagrilintide, KBP-series DACRAs, and investigational drugs, including ZP8396 and amycretin. Of particular interest, amylin-derived medications can have advantages over weight loss but definite disease-modifying action remains to be determined. Taken together, AMYRAs represent a potential category of therapeutics with promising disease-modifying effects that goes beyond weight loss, providing fresh perspectives for precision obesity management by 2030."

Journal • Review • Genetic Disorders • Metabolic Disorders • Obesity • CALCR

RENEW 1: Weight Loss in People Living With Overweight or Obesity Following Treatment With Cagrilintide (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

A Research Study to Investigate the Effects of CagriSema Compared to Placebo in People With Type 2 Diabetes and Painful Diabetic Peripheral Neuropathy (clinicaltrials.gov) - P2 | N=142 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Diabetic Neuropathy • Metabolic Disorders • Pain • Peripheral Neuropathic Pain • Type 2 Diabetes Mellitus

CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1. (PubMed, Hypertension) - P3 | "Fixed-dose combination of semaglutide/cagrilintide (CagriSema 2.4 mg/2.4 mg) has demonstrated significant and clinically relevant body weight reductions in adults with overweight or obesity compared with placebo. CagriSema presents clinically relevant reductions in BP across a wide range of participant subgroups, including those with resistant hypertension. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05567796."

Journal • Cardiovascular • Diabetes • Genetic Disorders • Hypertension • Metabolic Disorders • Obesity

RENEW 2: Weight Loss in People Living With Overweight or Obesity and Type 2 Diabetes Following Treatment With Cagrilintide (clinicaltrials.gov) - P3 | N=330 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

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

REIMAGINE 3: A Research Study to See How Much CagriSema Lowers Blood Sugar and Body Weight Compared to Placebo in People With Type 2 Diabetes Treated With Once-daily Basal Insulin With or Without Metformin (clinicaltrials.gov) - P3 | N=274 | Completed | Sponsor: Novo Nordisk A/S | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • LEP • LEPR

A Research Study on How Well Cagrilintide and CagriSema Work in Children and Adolescents With Excess Body Weight (clinicaltrials.gov) - P3 | N=460 | Not yet recruiting | Sponsor: Novo Nordisk A/S

Monotherapy • New P3 trial • Genetic Disorders • Obesity

A Research Study to See if Kidney Damage in People With Chronic Kidney Disease and Type 2 Diabetes Living With Overweight or Obesity Can be Reduced by CagriSema Compared to Semaglutide, Cagrilintide and Placebo (clinicaltrials.gov) - P2 | N=626 | Completed | Sponsor: Novo Nordisk A/S | Active, not recruiting ➔ Completed

Trial completion • Chronic Kidney Disease • Diabetes • Genetic Disorders • Metabolic Disorders • Nephrology • Obesity • Renal Disease • Type 2 Diabetes Mellitus • CST3

Cagrilintide-Semaglutide in Adults with Overweight or Obesity. Reply. (PubMed, N Engl J Med) - No abstract available

Journal • Genetic Disorders • Obesity

Cagrilintide-Semaglutide in Adults with Overweight or Obesity. (PubMed, N Engl J Med) - No abstract available

Journal • Genetic Disorders • Obesity

Synthetic target trial emulation and predictive modeling of amylin-pathway therapies for obesity and type 2 diabetes. (PubMed, Metabol Open) - "Network meta-analysis integrated evidence across CagriSema, cagrilintide, and amycretin formulations...Virtual head-to-head modeling confirmed CagriSema superiority over amycretin subcutaneous at matched timepoints (posterior probability >0.95)...Synthetic target trial emulation with structured validation (leave-trial-out, posterior predictive checks, simulation-based calibration) demonstrated promising evidence for amylin-pathway development optimization. Benefit-risk frontier analysis identified an optimal 10-20 mg subcutaneous therapeutic window, and heterogeneity quantification through maximum a posteriori (MAP) predictive interval provides design-ready estimates for confirmatory trials requiring around 800-1,200 participants per arm for 90 % power."

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

Exploration of Cagrilintide's Mechanism of Action in the Kidneys (KIDNEY WEEK 2025) - "Tubules were exposed to a phosphodiesterase inhibitor and then treated with vehicle, cagrilintide, or salmon calcitonin for 30min. Conclusion Our results point to a diabetes-specific mechanism by which cagrilintide elevates cAMP in cortical tubules, providing initial evidence of mode of action in diabetic kidney physiology compared with healthy controls. Ongoing phosphoproteomic analyses will offer deeper insights into the molecular pathways affected, potentially guiding the therapeutic application of cagrilintide in diabetic kidney disease."

Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Obesity • Renal Disease

Amylin and the renin-angiotensin system: risk or opportunity in amylin-based therapy? (PubMed, Lancet) - "We hypothesise that amylin receptor agonists (eg, pramlintide) and dual amylin and calcitonin-receptor agonists (eg, cagrilintide), which are emerging treatments for obesity and type 2 diabetes, can activate the renin-angiotensin system (RAS) and potentially undermine the cardiorenal benefits of these therapies...To test this, we propose: (1) preclinical studies investigating amylin-RAS interactions with or without RAS blockade; (2) post-hoc analyses of phase 2/3 trials stratified by RAS inhibitor use; (3) biomarker studies monitoring renin, aldosterone, angiotensin-(1-7), and ACE2; and (4) mechanistic human studies prospectively assessing cardiovascular-kidney metabolic effects by RAS inhibitor status. These suggestions aim to determine whether RAS inhibition enhances the overall efficacy of amylin-based therapies, and whether RAS blockers should be strongly recommended in patients receiving them."

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

REDEFINE 5: CagriSema in East Asian Adults With Overweight or Obesity, With or Without T2D (OBESITY WEEK 2025) - P3 | "Background: The combination of semaglutide (sema) 2.4 mg and cagrilintide 2.4 mg (CagriSema 2.4 mg/2.4 mg) has been shown to induce weight loss in adults with overweight and obesity in the REDEFINE 1 and 2 trials... CagriSema provided superior and clinically meaningful weight reduction and improvements in cardiometabolic risk factors in East Asian adults with overweight or obesity, with or without T2D, compared with sema. Safety and tolerability were comparable with other incretin-based therapies and previous trials of CagriSema."

Clinical • Diabetes • Dyslipidemia • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

CagriSema Reduces Predicted ASCVD Risk in Adults With Overweight or Obesity: The REDEFINE 1 Trial (OBESITY WEEK 2025) - P3 | "Adults (N=3417) with body mass index ≥30 kg/m2, or ≥27 kg/m2 with ≥1 obesity-related complication, without diabetes, were randomized 21:3:3:7 to receive CagriSema (n=2108), semaglutide (n=302), cagrilintide (n=302), or placebo (n=705), plus lifestyle intervention, for 68 weeks. After 68 weeks of treatment, CagriSema reduced the proportion of participants who were at intermediate–high risk of developing ASCVD within the next 10 years."

Clinical • Atherosclerosis • Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity

CagriSema Reduces hsCRP in Adults With Overweight or Obesity: the REDEFINE 1 Trial (OBESITY WEEK 2025) - P3 | "Participants were randomized 21:3:3:7 to CagriSema (n=2108), semaglutide (n=302), cagrilintide (n=302), or placebo (n=705) for 68 weeks, plus lifestyle intervention... At baseline, mean (standard deviation) age was 47.0 (11.8) years and 67.6% of participants were female; 14.9% of participants were on statins, 0.5% on systemic glucocorticoids, 0.4% on colchicine, and 13.3% were current smokers... CagriSema treatment for 68 weeks appeared to reduce hsCRP across all baseline hsCRP levels, and independent of the other baseline characteristics assessed in participants with overweight or obesity. In a mediation analysis, the hsCRP reductions with CagriSema were not solely driven by weight loss. These results suggest a potential anti-inflammatory effect of CagriSema in people with overweight or obesity that may lower CV risk."

Clinical • Cardiovascular • Diabetes • Genetic Disorders • Inflammation • Metabolic Disorders • Obesity • CRP

CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: The REDEFINE 1 Trial (OBESITY WEEK 2025) - P3 | "Participants (N=3417) were randomized 21:3:3:7 to CagriSema (n=2108), semaglutide (n=302), cagrilintide (n=302), or placebo (n=705), and lifestyle intervention, for 68 weeks. CagriSema significantly reduced blood pressure in participants with overweight or obesity, irrespective of whether their baseline BMI was greater than or less than 35 kg/m2. This was associated with reduced use of antihypertensive medication in those on medication at baseline. These data reveal a marked, previously unrecognized antihypertensive benefit of CagriSema—an important advance given that hypertension remains refractory in people with obesity and is the leading driver of cardiovascular disease worldwide."

Clinical • Cardiovascular • Diabetes • Genetic Disorders • Hypertension • Metabolic Disorders • Obesity

Effect of CagriSema 2.4mg/2.4mg on Body Composition, Muscle Strength & Physical Function: REDEFINE 1 (OBESITY WEEK 2025) - " REDEFINE 1, a phase 3a, double-blind, placebo- and active-controlled study randomized 3417 participants with BMI ≥30 kg/m2, or ≥27 kg/m2 with ≥1 obesity-related complication, in a 21:3:3:7 ratio to once-weekly subcutaneous CagriSema 2.4 mg/2.4 mg, semaglutide 2.4 mg, cagrilintide 2.4 mg, or placebo, plus lifestyle intervention for 68 weeks. In REDEFINE 1, the improvements in fat-to-lean soft tissue mass ratio were associated with improvements in physical function, and there was no decline in muscle strength compared with placebo."

Genetic Disorders • Obesity • Sarcopenia

CagriSema and Achievement of BMI and Waist-to-Height Ratio Treatment Targets: REDEFINE 1 (OBESITY WEEK 2025) - " Participants (BMI ≥30 kg/m2, or ≥27 kg/m2 with ≥1 ORC) were randomized in a double-blind manner to CagriSema, semaglutide, cagrilintide or placebo, as add-on to lifestyle intervention, for 68 weeks. In this analysis of REDEFINE 1, a greater proportion of participants treated with CagriSema achieved clinically relevant treatment targets vs comparators. These data highlight the link between new targets in the clinical management of obesity, achieved by nearly a third of participants exposed to CagriSema, and normalization of cardiometabolic parameters."

Genetic Disorders • Obesity • CRP

Eloralintide, a Selective Amylin Analog, Improves Insulin Sensitivity in Diet-induced Obese Rats (OBESITY WEEK 2025) - "Herein, we present eloralintide, a selective amylin analog, that we previously showed had potent effects on weight loss efficacy and body composition changes (fat and lean mass ratios) in DIO rats compared to the non-selective amylin, cagrilintide. Eloralintide, a selective amylin receptor agonist, demonstrated weight loss primarily driven by fat mass reductions, and weight-independent improvements in glucose homeostasis mediated by insulin sensitivity in DIO rats after chronic administration. These findings support clinical investigation of eloralintide as an obesity management medication."

Preclinical • Genetic Disorders • Obesity

Weight Loss, Obesity Medication, and Risk of Obesity-Associated Cancer: A Meta-Analysis of Randomized Controlled Trials. (PubMed, Obesity (Silver Spring)) - "Weight reduction mediated by current AOMs was not associated with a reduced risk of overall or site-specific obesity-associated cancer in patients with overweight or obesity, while a decreased risk of overall obesity-associated cancer was observed in coagonist users."

Journal • Retrospective data • Review • Genetic Disorders • Obesity • Oncology

A Research Study to See How Well CagriSema Compared to Tirzepatide Helps People With Obesity Lose Weight (clinicaltrials.gov) - P3 | N=809 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Trial primary completion date: Aug 2025 ➔ Dec 2025

Trial primary completion date • Genetic Disorders • Obesity

RENEW 1: Weight Loss in People Living With Overweight or Obesity Following Treatment With Cagrilintide (clinicaltrials.gov) - P3 | N=300 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P3 trial • Genetic Disorders • Obesity

RENEW 2: Weight Loss in People Living With Overweight or Obesity and Type 2 Diabetes Following Treatment With Cagrilintide (clinicaltrials.gov) - P3 | N=330 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P3 trial • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus