cagrilintide (AM833) / Novo Nordisk - LARVOL DELTA

New Amylin-Based Agonists for the Treatment of Obesity and Type 2 Diabetes Mellitus. (PubMed, Diabetes Ther) - "These agents hold therapeutic potential in the management of both T2DM and obesity, as shown by preliminary clinical trial outcomes. Further trials are now needed to validate them in clinical practice."

Journal • Review • Anorexia • Diabetes • Fatigue • Genetic Disorders • Metabolic Disorders • Obesity • Pain • Type 2 Diabetes Mellitus

Efficacy and Safety of CagriSema for Metabolic Outcomes: Systematic Review and Pairwise Meta-Analysis of Randomized Controlled Trials. (PubMed, Diabetes Metab Syndr Obes) - "To evaluate the efficacy and safety of dual-agonist CagriSema vs semaglutide monotherapy, cagrilintide monotherapy, and placebo in adults with overweight/obese status and type 2 diabetes, we searched Embase, MEDLINE, PubMed, and the Cochrane Library up to 14 June 2026 for randomized controlled trials (RCTs)...Compared with current standard monotherapies and placebos, CagriSema demonstrates superior weight loss, glucose, and lipid control. Key limitations include the relatively small number of eligible trials and the current lack of long-term cardiovascular endpoints."

Journal • Retrospective data • Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • CRP

Cagrilintide and retatrutide combination therapy enhances weight loss and metabolic outcomes in obese male rats. (PubMed, Nat Metab) - "Peptide multi-receptor agonists have advanced obesity treatment, yet challenges remain in achieving maximal weight loss and metabolic control, especially in patients with obesity and type 2 diabetes...Daily co-administration produces dose-dependent reductions in body weight and food intake that exceed both equimolar monotherapies and matched-dose comparator combinations incorporating semaglutide or tirzepatide...Plasma proteomic profiling highlights enrichment of bioenergetic processes with the combination therapy, whereas brain transcriptomic profiling identifies convergent central neuronal programmes linked to energy balance regulation. Collectively, our preclinical findings support five-receptor polypharmacology as a strategy for efficaciously lowering body weight and provide guidance for the design of next-generation unimolecular multi-receptor agonists."

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

Impact of Cagrilintide 2.4 Mg on Cardiometabolic Risk Indicators: A Post-Hoc Analysis of REDEFINE 1 (OBESITY WEEK 2026) - No abstract available

Retrospective data • Inflammation

VRB-103 is a potent, orally bioavailable amylin analog with a strong selectivity towards human amylin receptors versus calcitonin receptor (EASD 2026) - "Clinical stage amylin analogs, such as cagrilintide and eloralintide, have demonstrated distinct profiles for tolerability and body weight reduction with weekly subcutaneous administrations. VRB-103 is a potent and orally bioavailable amylin analog with a strong selectivity towards human amylin receptors relative to hCTR. The amylin receptor selectivity of VRB-103 was more pronounced than that of the comparators analyzed. VRB-103 is currently in development as a once-weekly oral tablet for obesity."

Metabolic Disorders • Obesity

A novel unimolecular tetra-agonist peptide targeting GLP-1, GIP, amylin and calcitonin receptors produces superior weight loss efficacy and quality than tirzepatide or CagriSema in obese rats (EASD 2026) - "Materials and DIO rats received PTT-A (10 or 30 nmol/kg), tirzepatide (30 nmol/kg), or CagriSema (2 nmol/kg cagrilintide plus 2 nmol/kg semaglutide) for 21 days... PTT-A achieves greater and more selective weight loss than tirzepatide or CagriSema, driven by enhanced fat loss and lean mass preservation. These findings highlight our tetra-agonism approach as a promising next generation therapy for treating obesity and its metabolic complications, with the potential for sustained efficacy and acceptable safety."

Preclinical • Metabolic Disorders • Obesity

Research Study on How People With Type 2 Diabetes Tolerate Switching From Semaglutide to Cagrisema (clinicaltrials.gov) - P3 | N=210 | Not yet recruiting | Sponsor: Novo Nordisk A/S

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

REIMAGINEYOUNG: A Research Study to See How Much CagriSema Lowers Blood Sugar and Body Weight Compared to Placebo in Children and Adolescents With Type 2 Diabetes (clinicaltrials.gov) - P3 | N=80 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • LEP • LEPR

Cagrilintide Reduces Body Weight and Prevents Adiposity Gain in Diet-Induced Obese Rats (OBESITY WEEK 2026) - No abstract available

Preclinical • 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 | Completed | Sponsor: Novo Nordisk A/S | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Diabetic Neuropathy • Metabolic Disorders • Peripheral Neuropathic Pain • Type 2 Diabetes Mellitus

Cagrilintide a Dual Amylin and Calcitonin Receptor Agonist Protects Bone Mass During Weight Loss (OBESITY WEEK 2026) - No abstract available

Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists and Co-agonists for Weight Loss Among Adults Without Diabetes : An Updated Systematic Review. (PubMed, Ann Intern Med) - "To update our prior systematic review evaluating the efficacy and safety of GLP-1 RAs and co-agonists among adults with overweight or obesity without diabetes...Among commercially available therapies, placebo-subtracted weight loss reached up to -5.8% (95% CI, -8.0% to -3.6%) for liraglutide, -14.8% (CI, -16.2% to -13.4%) for subcutaneous semaglutide, -14.3% (CI, -17.2% to -11.4%) for oral semaglutide, -12.4% (CI, -15.1% to -9.7%) for orforglipron, and -19.0% (CI, -21.6% to -16.4%) for tirzepatide. Numerically greater placebo-subtracted reductions were seen with emerging multiagonists, including -23.9% (CI, -29.3% to -18.5%) with amycretin and -22.1% (CI, -24.9% to -19.3%) with retatrutide...Head-to-head data showed greater weight loss with semaglutide and JNJ-64565111 than liraglutide and greater weight loss with tirzepatide and cagrilintide-semaglutide (CagriSema; Novo Nordisk) than semaglutide...None. (PROSPERO: CRD42024505558)."

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

Comparative efficacy and safety of glucagon-like peptide 1 based drugs for weight loss in adults with overweight or obesity without diabetes: network meta-analysis of randomised controlled trials. (PubMed, BMJ Med) - "Compared with placebo, weight loss was greatest with retatrutide (-22.10%, 95% confidence interval -25.60% to -18.60%), followed by tirzepatide (-19.28%, -20.39% to -18.16%), and CagriSema (a combination of cagrilintide and semaglutide, -17.32%, -19.32% to -15.32%)...Low certainty evidence suggested higher rates for discontinuing treatment with danuglipron and retatrutide, whereas mazdutide showed better tolerability...Differences in tolerability, limited head-to-head evidence, and residual uncertainty, however, should be considered when interpreting comparative treatment effects. PROSPERO CRD420261279841."

Journal • Retrospective data • Diabetes • Endocrine Disorders • Genetic Disorders • Metabolic Disorders • Obesity

Beneficial effect of the combinatorial therapy of sub-maximal doses of cagrilintide and tirzepatide on body weight loss in obese rats (EASD 2026) - "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, highlighting the potential of combining these complementary therapies for the treatment of obesity and metabolic disorders."

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

A Study to See How Metabolism is Influenced by Weight Loss Due to Intervention With Cagrilintide and Semaglutide Compared to Diet (clinicaltrials.gov) - P1 | N=80 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2027 ➔ Feb 2028

Enrollment closed • Trial completion date • Genetic Disorders • Obesity

A Research Study to Compare Blood Levels of Two Different Versions of Cagrilintide in Adults With Excess Body Weight (clinicaltrials.gov) - P1 | N=50 | Completed | Sponsor: Novo Nordisk A/S | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Obesity

RENEW 4: A Research Study to Compare Two Different Versions of Injectable Cagrilintide and Placebo in People With Excess Body Weight (clinicaltrials.gov) - P3 | N=285 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

Effect of CagriSema on continuous glucose monitoring in people with inadequately controlled type 2 diabetes: REIMAGINE 2 (EASD 2026) - P3 | "Clinical Trial Registration Number: NCT06065540 Background and aims: In REIMAGINE 2, CagriSema, a fixed-dose cagrilintide and semaglutide combination, significantly reduced HbA 1c and body weight (BW) vs its monocomponents in people with type 2 diabetes (T2D) inadequately controlled on metformin ± sodium- glucose cotransporter-2 inhibitor, and overweight/obesity. CagriSema 2.4 mg/2.4 mg and semaglutide 2.4 mg led to clinically relevant improvements in TIR, TITR, PPG curves and TtN. Improvements with CagriSema 2.4 mg/2.4 mg were greatest in people with BL BMI ≥35 kg/m 2; semaglutide 2.4 mg efficacy was consistent regardless of BL BMI. These data support this combination therapy for improved glucose control, especially in people with BMI ≥35 kg/m 2 ."

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

Effect of CagriSema on bone biomarkers in participants with inadequately controlled type 2 diabetes: REIMAGINE 2 (EASD 2026) - P3 | "Treatment with CagriSema, a fixed-dose combination of cagrilintide and semaglutide, leads to substantial weight loss in people with T2D (14.2% weight reduction with CagriSema 2.4 mg/2.4 mg at week 68 in the REIMAGINE 2 trial). CagriSema was associated with changes in CTX-1 and P1NP, that are consistent with reactivation of bone remodelling, in this population with T2D. Even with the substantial weight reduction observed with CagriSema, the stabilisation of CTX-1, coupled with the increase in P1NP from week 20 to 68 provides preliminary reassurance regarding bone changes with CagriSema in T2D."

Biomarker • Late-breaking abstract • Diabetes • Metabolic Disorders • Osteoporosis • Type 2 Diabetes Mellitus

Amylin monotherapy: the road paved by cagrilintide (EASD 2026) - "Sponsored by Novo Nordisk A/S"

Monotherapy • Metabolic Disorders

Agonism of amylin and calcitonin receptors via cagrilintide, CagriSema and zenagamtide are beneficial for bone health in a rat model of ovariectomy-induced osteoporosis (EASD 2026) - "Alendronate (10 ug/kg) and sham operated animals served as a positive and healthy controls, respectively...Weight matching by energy restriction reduced bone formation, as reflected by P1NP levels, compared to vehicle and this decrease was ameliorated after treatment with cagrilintide, semaglutide, CagriSema or zenagamtide (p<0.05) suggesting an overall net- beneficial effect on bone turnover... Cagrilintide, CagriSema, and zenagamtide ameliorated bone loss and structural deterioration in OVX rats. This was not observed to a similar extent with the GLP1R agonist semaglutide, thereby, suggesting a uniquely beneficial effects of these AMYR/CTR agonists for bone health. Thus, such amylin agonist may promote a healthier weight loss in patients by mitigating bone loss."

Preclinical • Metabolic Disorders • Obesity • Osteoporosis • COL1A2

Impact of cagrilintide 2.4 mg on physical function: post-hoc patient-reported outcomes from REDEFINE 1 (EASD 2026) - P3 | "Materials and REDEFINE 1 was a phase 3 trial that randomised (21:3:3:7) adults without diabetes and with BMI ≥30 kg/m 2 or ≥27 kg/m 2 and at least one obesity-related complication to CagriSema 2.4 mg/2.4 mg, semaglutide 2.4 mg, cagrilintide 2.4 mg, or placebo for 68 weeks... Cagrilintide 2.4 mg monotherapy improved physical function in people with overweight or obesity."

Clinical • Patient reported outcomes • Retrospective data • Diabetes • Metabolic Disorders • Obesity

Relationship between mean CagriSema dose and weight loss in the REDEFINE 1 trial (EASD 2026) - P3 | "Materials and In the phase 3 REDEFINE 1 trial, 3417 adults with a BMI ≥30 kg/m 2 , or ≥27 kg/m 2 with ≥1 obesity-related complication, were randomised 21:3:3:7 to receive once-weekly CagriSema (n=2108), semaglutide (n=302), cagrilintide (n=302) or placebo (n=705)... Substantial, clinically relevant weight losses were observed across all dose groups of CagriSema. The lack of a clear linear relationship between mean dose administered and relative weight loss indicates heterogeneity in effect, with some participants highly responsive to submaximal doses."

Metabolic Disorders • Obesity

Superior efficacy and clinical translatability of CagriSema compared to cagrilintide and semaglutide in diet-induced obese rats (EASD 2026) - "CagriSema demonstrates greater body weight loss efficacy in DIO rats than Cagrilintide and Semaglutide alone, consistent with clinical findings. CagriSema preferentially mobilizes metabolically harmful visceral fat, reduces intramuscular adipocyte load and induces skeletal muscle remodeling commensurate with reduced body mass."

Preclinical • Metabolic Disorders • Obesity

Arcuate hypothalamic CTR-expressing neurons regulate feeding but are not required for cagrilintide-induced hypophagia in mice (EASD 2026) - "Together, these findings define a mouse hypothalamic circuit involved in feeding control and inform interpretation of species-specific differences in amylin receptor circuitry relevant to translational efficacy."

Preclinical • Metabolic Disorders • Obesity • CALCR