amylin long acting (AZD6234) / AstraZeneca - LARVOL DELTA

Co-Administration of GLP-1R/GCGR and Amylin Receptor Agonists Improves Body Weight in DIO Rats (OBESITY WEEK 2025) - "We aimed to evaluate the combination effects of AZD6234 and the GLP-1R/GCGR agonist cotadutide (cota) on BW gain in obese (DIO) rats, and acute effects on GE in chow fed rats. DIO rats treated with a combination of AZD6234 and cota displayed an additive effect on decreasing BW gain vs. monotherapy accompanied by a decrease in peri-renal fat pad and liver weights. Treatment with AZD6234 or cota showed an expected decrease in GE in dose-dependent manner, and an additional effect on GE was observed with combination treatment at sub-maximal doses as compared to monotherapy."

Preclinical • Genetic Disorders • Obesity

A Study to Investigate the Effect of AZD6234 and a Combination of AZD9550 and AZD6234 on Pharmacokinetics of Combined Oral Contraceptive Ethinyl Estradiol/Levonorgestrel in Healthy Female Participants Living With Overweight or Obesity (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Jan 2026 ➔ Jul 2026 | Trial primary completion date: Jan 2026 ➔ Jul 2026

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

Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD6234 (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: AstraZeneca | N=100 ➔ 24 | Trial completion date: Jan 2026 ➔ Sep 2025 | Trial primary completion date: Jan 2026 ➔ Sep 2025 | Recruiting ➔ Completed

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Renal Disease

A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD6234 After Repeat Dose Administration in Participants Who Are Overweight or Obese (clinicaltrials.gov) - P1 | N=103 | Active, not recruiting | Sponsor: AstraZeneca | N=52 ➔ 103

Enrollment change • Genetic Disorders • Obesity

ASCEND: A Weight Loss Study Evaluating Subcutaneous Treatment With AZD9550 and AZD6234 in Combination Against Placebo or Each of the Drugs Alone (clinicaltrials.gov) - P2 | N=377 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

A Study to Assess the Relative Bioavailability of Different Subcutaneous Formulations ofAZD6234 (clinicaltrials.gov) - P1 | N=21 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial • Genetic Disorders • Obesity

ARAY: Efficacy, Safety and Tolerability of AZD6234 in Participants Living With Overweight or Obesity With Type 2 Diabetes Who Are on a Stable Dose of GLP-1 Receptor Agonist (clinicaltrials.gov) - P2 | N=64 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Feb 2026 ➔ Jul 2026 | Trial primary completion date: Feb 2026 ➔ Jul 2026

Trial completion date • Trial primary completion date • Diabetes • Endocrine Disorders • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

AZD234, a novel selective amylin receptor agonist (SARA), demonstrates a preferential profile over DACRA or GLP-1R agonist in rat models of aversion and fat-mass loss (EASD 2025) - "Our data indicate that AZD6234, a potent SARA, elicited fat-mass specific weight loss with preservation of lean-mass in DIO rats. In lean rats, aversion correlated to calcitonin receptor engagement and in DIO rats lean mass loss also correlated to calcitonin receptor engagement. AZD6234 mediated significant delay in gastric emptying which unlike GLP-1RA was maintained beyond 7 days."

Preclinical • Metabolic Disorders • Obesity

A Study to Investigate the Effect of AZD6234 and a Combination of AZD9550 and AZD6234 on Pharmacokinetics of Combined Oral Contraceptive Ethinyl Estradiol/Levonorgestrel in Healthy Female Participants Living With Overweight or Obesity (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: AstraZeneca | N=25 ➔ 50

Enrollment change • Genetic Disorders • Obesity

A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD6234 After Repeat Dose Administration in Participants Who Are Overweight or Obese (clinicaltrials.gov) - P1 | N=52 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting | N=142 ➔ 52

Enrollment change • Enrollment closed • Genetic Disorders • Obesity

A Study to Assess the Impact of Multiple Doses of AZD6234 on a Single Dose of Combined Oral Contraceptive in Female Participants (clinicaltrials.gov) - P1 | N=25 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

Long-Acting Amylin Analog AZD6234 in Combination with the GLP-1R Agonist Semaglutide Enhances Body Weight and Fat Mass Loss in Diet-Induced Obese (DIO) Rats (ADA 2025) - "Treatment with AZD6234 and semaglutide showed similar BW loss, but AZD6234 treatment led to more fat mass loss with the preservation of lean mass. Combined treatment led to additive effects on suppression of food intake, BW and fat mass loss."

Combination therapy • Preclinical • Metabolic Disorders • Obesity

This is a Multi-centre, Multi-drug, Platform Study in Chinese Participants Living With Obesity/Overweight (clinicaltrials.gov) - P2 | N=871 | Recruiting | Sponsor: AstraZeneca

New P2 trial • Genetic Disorders • Obesity

A Study to Assess the Impact of Multiple Doses of AZD6234 on a Single Dose of Combined Oral Contraceptive in Female Participants (clinicaltrials.gov) - P1 | N=25 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial • Genetic Disorders • Obesity

Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD6234 (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Oct 2025 ➔ Jan 2026 | Trial primary completion date: Oct 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • Renal Disease

ARAY: Efficacy, Safety and Tolerability of AZD6234 in Participants Living With Overweight or Obesity With Type 2 Diabetes Who Are on a Stable Dose of GLP-1 Receptor Agonist (clinicaltrials.gov) - P2 | N=64 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

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

Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD6234 (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Renal Disease

ASCEND: A Weight Loss Study Evaluating Subcutaneous Treatment With AZD9550 and AZD6234 in Combination Against Placebo or Each of the Drugs Alone (clinicaltrials.gov) - P2 | N=360 | Recruiting | Sponsor: AstraZeneca

New P2 trial • Genetic Disorders • Obesity

Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD6234 (clinicaltrials.gov) - P1 | N=100 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial • Renal Disease

ARAY: Efficacy, Safety and Tolerability of AZD6234 in Participants Living With Overweight or Obesity With Type 2 Diabetes Who Are on a Stable Dose of GLP-1 Receptor Agonist (clinicaltrials.gov) - P2 | N=64 | Not yet recruiting | Sponsor: AstraZeneca

New P2 trial • Diabetes • Endocrine Disorders • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

APRICUS: A Study in Participants With Obesity or Overweight With at Least One Weight-related Comorbidity (clinicaltrials.gov) - P2 | N=262 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD6234 After Repeat Dose Administration in Participants Who Are Overweight or Obese (clinicaltrials.gov) - P1 | N=142 | Recruiting | Sponsor: AstraZeneca | N=76 ➔ 142 | Trial completion date: Apr 2025 ➔ Feb 2026 | Trial primary completion date: Apr 2025 ➔ Feb 2026

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

Amylin Receptor Agonist AZD6234 Shows Advantages Over GLP-1R Activation for Leptin Re-Sensitization (OBESITY WEEK 2024) - "When treating obese rats for two weeks with semaglutide or AZD6234, AZD6234 better restores leptin sensitization in the hypothalamus and decreases endogenous leptin levels to those seen in lean controls. AZD6234 also drives greater reduction in fat mass compared GLP-1R agonism, despite similar body weight reduction."

Genetic Disorders • Obesity • LEP

APRICUS: A Study in Participants With Obesity or Overweight With at Least One Weight-related Comorbidity (clinicaltrials.gov) - P2 | N=231 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting | Trial primary completion date: Jan 2026 ➔ Oct 2025

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

Treatment With a Long-acting Amylin, AZD6234, Leads Body Weight Loss With Preservation of Lean Mass (OBESITY WEEK 2024) - "AZD6234 treatment showed fat mass specific weight loss with greater preservation of lean mass, compared to semaglutide. Cessation of either treatment showed similar body weight regain with a rebound of type of mass originally lost."

Genetic Disorders • Obesity