AZD6234
Medium EvidenceAZD6234 is an investigational, long-acting selective amylin receptor agonist (SARA) from AstraZeneca, given once weekly by subcutaneous injection and developed for chronic weight management in adults with obesity or overweight. Amylin is a natural pancreatic hormone that works alongside insulin to signal fullness, slow stomach emptying and reduce food intake, and a wave of amylin-based drugs is being pursued as a better-tolerated alternative or partner to GLP-1 medicines such as semaglutide and tirzepatide. AZD6234 is engineered as a synthetic long-acting pramlintide analog whose balance of activity at the amylin receptor (AMY3R) versus the calcitonin receptor is tuned to mimic native amylin, and in animal studies it produced fat-selective weight loss while sparing lean mass and showed less nausea/aversion signaling than some rival approaches. It is now in Phase 2, including a factorial obesity study testing AZD6234 alone, AstraZeneca's GLP-1/glucagon dual agonist AZD9550 alone, and the two combined, versus placebo. AZD6234 is not approved by the FDA or any regulator for any use.
What It Is
AZD6234 is a long-acting, subcutaneously administered selective amylin receptor agonist (SARA) being developed by AstraZeneca as part of its cardiometabolic and obesity pipeline. Amylin (islet amyloid polypeptide, IAPP) is co-secreted with insulin from pancreatic beta cells and acts on amylin receptors - complexes of the calcitonin receptor (CTR) with receptor-activity-modifying proteins (RAMPs), designated AMY1-3 - in hindbrain and hypothalamic circuits to promote satiation, slow gastric emptying and lower food intake. The first amylin analog to reach the clinic, pramlintide, is short-acting and requires mealtime dosing; the current generation, including AZD6234, cagrilintide, petrelintide and eloralintide, is engineered for once-weekly dosing. AZD6234 is described as a synthetic long-acting pramlintide analog whose amylin-receptor (AMY3R) versus calcitonin-receptor selectivity ratio is designed to reproduce that of native amylin, making it a highly potent AMY3R agonist with a selectivity profile over the CTR matching pramlintide. In rodent models AstraZeneca reported that AZD6234 drives weight loss chiefly by reducing food intake, favors loss of fat mass over lean mass, and shows a preferential profile - less aversive (nausea-like) signaling - compared with dual amylin/calcitonin receptor agonists (DACRAs) or a GLP-1 receptor agonist, and that combining AZD6234 with semaglutide enhanced body-weight and fat-mass loss in diet-induced obese rats. AZD6234 has completed Phase 1 in healthy volunteers (well tolerated, no deaths or serious adverse events) and is in a Phase 2 program that includes a reduced-factorial obesity study of AZD6234 monotherapy, the GLP-1/glucagon dual agonist AZD9550 monotherapy, the AZD6234 + AZD9550 combination, and placebo, plus studies of AZD6234 added to existing incretin (GLP-1) therapy in people with type 2 diabetes. AZD6234 remains investigational and is not approved for any indication.
Regulatory Status
AZD6234 is an investigational long-acting selective amylin receptor agonist (SARA) from AstraZeneca and is not approved by the FDA or any other regulatory agency for obesity, weight management or any other indication. It is a once-weekly subcutaneous synthetic long-acting pramlintide analog that selectively activates the amylin receptor (AMY3R). Following Phase 1 testing in healthy volunteers (well tolerated, no deaths or serious adverse events), AZD6234 is in a Phase 2 program centered on a reduced-factorial obesity trial (NCT06862791 / D8460C00004) comparing AZD6234 monotherapy, the GLP-1/glucagon dual agonist AZD9550 monotherapy, the AZD6234 + AZD9550 combination, and placebo in adults with obesity or overweight plus a weight-related comorbidity, alongside a combination safety study (NCT06151964) and studies of AZD6234 added to a stable GLP-1 receptor agonist in type 2 diabetes with obesity/overweight (NCT06851858). As of September 2026, AstraZeneca had not publicly disclosed detailed Phase 2 efficacy data. AZD6234 should be regarded as an experimental compound available only through authorized clinical trials.
Why Researchers Study It
Researchers study AZD6234 because amylin has emerged as the most promising new backbone for obesity medicine after GLP-1, and AstraZeneca's molecule is a distinctive bet within that wave. The appeal of amylin agonists is that they can produce substantial weight loss while causing less nausea and vomiting than GLP-1 drugs, which could improve tolerability, adherence and the ceiling of achievable weight loss. AZD6234 is engineered as a 'selective' amylin receptor agonist (SARA), meaning its balance of activity at the amylin receptor versus the calcitonin receptor is tuned to look like the natural hormone; in animal studies AstraZeneca reported that this profile yields fat-selective weight loss with preservation of lean mass and a lower aversion (nausea-like) signal than dual amylin/calcitonin agonists or a GLP-1 drug. The second reason AZD6234 is closely watched is combination strategy: rather than pursuing amylin alone, AstraZeneca is testing it head-to-head and together with AZD9550, a GLP-1/glucagon dual agonist, in a single factorial trial - an efficient way to ask whether pairing an amylin agonist with an incretin backbone delivers additive, fat-selective weight loss and metabolic benefit. Because amylin also slows gastric emptying and enhances satiety through pathways distinct from GLP-1, it offers a mechanistically complementary lever, and AZD6234 is a key clinical test of whether next-generation, once-weekly amylin agonists can match GLP-1-class efficacy with a gentler side-effect profile.
Proposed Mechanisms
- Amylin receptor (AMY3R) agonism: AZD6234 is a long-acting synthetic pramlintide analog that potently activates the amylin receptor - a complex of the calcitonin receptor (CTR) with a receptor-activity-modifying protein (RAMP) - with a selectivity over the CTR designed to match native amylin, hence 'selective amylin receptor agonist (SARA).'
- Central control of appetite: activation of amylin receptors in hindbrain (area postrema/nucleus tractus solitarius) and hypothalamic circuits promotes satiation and reduces food intake, the principal driver of the weight loss seen in preclinical models.
- Delayed gastric emptying and meal termination: like native amylin and pramlintide, AZD6234 is expected to slow gastric emptying and reinforce meal-ending signals, complementing incretin (GLP-1) mechanisms.
- Fat-selective weight loss: in rodent studies AZD6234 preferentially reduced fat mass while sparing lean mass, an outcome of interest for preserving muscle during weight reduction.
- Reduced aversion signaling: preclinical aversion models suggested AZD6234 causes less nausea-like/aversive response than dual amylin/calcitonin receptor agonists (DACRAs) or a GLP-1R agonist, the tolerability rationale for a selective amylin agonist.
- Combination with incretins: AZD6234 is being paired with the GLP-1/glucagon dual agonist AZD9550 to test whether amylin plus incretin signaling produces additive, fat-selective weight loss and broader cardiometabolic benefit.
Evidence Snapshot
| Study Type | Model | Outcome | Link |
|---|---|---|---|
| Preclinical pharmacology - receptor characterization and rodent weight-loss/aversion models (presented at EASD 2025). | In vitro potency at human and rat amylin (AMY3R) and calcitonin (CTR) receptors via cAMP accumulation, plus diet-induced obese (DIO) rat and rat aversion (kaolin/conditioned taste aversion) models comparing AZD6234 with DACRA and GLP-1R agonist comparators. | AZD6234 was a highly potent AMY3R agonist with an AMY3R/CTR selectivity ratio matching pramlintide; it produced weight loss driven by reduced food intake, favored fat-mass over lean-mass loss, and showed a preferential (less aversive) profile versus DACRA or GLP-1R agonist comparators, supporting a selective-amylin-agonist (SARA) rationale. | Source |
| Preclinical combination study - AZD6234 + semaglutide in DIO rats (ADA 2025, abstract 88-OR). | Diet-induced obese rats treated with the long-acting amylin analog AZD6234, the GLP-1R agonist semaglutide, or the combination. | Adding AZD6234 to semaglutide enhanced body-weight and fat-mass loss beyond either agent alone, supporting clinical development of amylin + incretin combinations. | Source |
| Phase 1 first-in-human study in healthy participants. | Randomized, placebo-controlled single-/multiple-ascending-dose evaluation of subcutaneous AZD6234 for safety, tolerability and pharmacokinetics. | AZD6234 was well tolerated with no deaths and no serious adverse events reported, supporting advancement into Phase 2 obesity trials (detailed data not fully disclosed). | Source |
| Phase 2b obesity trial - reduced factorial (NCT06862791 / AstraZeneca D8460C00004); ongoing/completed enrollment. | Global, randomized, double-blind, placebo-controlled study of ~360 adults with obesity or overweight plus at least one weight-related comorbidity (hypertension, dyslipidemia or obstructive sleep apnea) across ~60 sites in ~7 countries; arms compare AZD6234 monotherapy, the GLP-1/glucagon dual agonist AZD9550 monotherapy, the AZD6234 + AZD9550 combination, and placebo; total study duration ~47 weeks. | Evaluating percentage change in body weight and safety/tolerability of AZD6234 alone and combined with AZD9550 versus placebo; detailed efficacy results not publicly disclosed as of September 2026 (outcomes pending). | Source |
Commonly Discussed Benefits
Researching AZD6234? Track it, set reminders, and keep notes in the free app.
Safety & Cautions
- AZD6234 is an investigational compound that is NOT approved by the FDA or any regulator for obesity, weight loss or any other use. It is studied only within clinical trials under medical supervision; any product sold as 'AZD6234' outside a legitimate trial is unverified and should not be used.
- As an amylin receptor agonist, the most likely class side effects are gastrointestinal - nausea, vomiting and reduced appetite - and injection-site reactions; a central rationale for selective amylin agonists is better GI tolerability than GLP-1 drugs, but human tolerability for AZD6234 specifically will only be established once Phase 2 data are reported.
- Because amylin slows gastric emptying, amylin-based drugs can alter the absorption of other oral medications and may raise the risk of hypoglycemia when combined with insulin or insulin secretagogues in people with diabetes.
- Much of the supporting evidence to date is preclinical (rodent models) or early-phase; long-term efficacy, safety, cardiovascular outcomes and durability of weight loss for AZD6234 in humans have not yet been established.
- AZD6234 is being developed partly in combination with the GLP-1/glucagon dual agonist AZD9550; combination regimens can have additive gastrointestinal and metabolic effects that require dedicated safety evaluation.
- This profile is educational information about a compound under investigation, not medical advice; decisions about weight-management therapy should be made with a qualified clinician.
Comparisons
See how AZD6234 compares to related peptides:
Calculator Tools
Use our research tools to explore dosing and reconstitution data:
Citations
- [1] A Weight Loss Study Evaluating Subcutaneous Treatment With AZD9550 and AZD6234 in Combination Against Placebo or Each of the Drugs Alone - ClinicalTrials.gov NCT06862791 PubMed
- [2] A Weight Loss Study Evaluating Subcutaneous Treatment With AZD9550 and AZD6234 (D8460C00004) - AstraZeneca Clinical Trials PubMed
- [3] A Trial to Learn How Safe AZD9550 Monotherapy and Combined With AZD6234 Is - ClinicalTrials.gov NCT06151964 PubMed
- [4] Efficacy, Safety and Tolerability of AZD6234 in Participants With Overweight or Obesity With Type 2 Diabetes on a Stable GLP-1 RA - ClinicalTrials.gov NCT06851858 PubMed
- [5] 88-OR: Long-Acting Amylin Analog AZD6234 in Combination with the GLP-1R Agonist Semaglutide Enhances Body Weight and Fat Mass Loss in DIO Rats - Diabetes (ADA 2025) PubMed
- [6] Amylin: From Mode of Action to Future Clinical Potential in Diabetes and Obesity - PMC PubMed
- [7] AZD6234 - AstraZeneca reveals oral GLP-1 scored phase 2 wins but holds back weight loss data - Fierce Biotech PubMed
- [8] AZD6234 drug profile - Synapse (PatSnap) PubMed
Keep researching in the app
- Log AZD6234 to your private tracker
- Set a dosing reminder
- Compare it side-by-side with your stack
Related Peptides
Amycretin
Medium EvidenceA unimolecular GLP-1 and amylin receptor dual agonist in Phase 3 trials, available in both subcutaneous and oral formulations, with up to 22% weight loss in Phase 1b/2a.
Cagrilintide
High EvidenceA long-acting amylin analog studied for appetite regulation; NDA filed for CagriSema (cagrilintide + semaglutide) combination in December 2025, with FDA review expected in 2026.
Eloralintide
Medium EvidenceA selective, long-acting amylin receptor agonist in Phase 3 trials for obesity, offering a GLP-1-independent weight loss mechanism with up to 20.1% weight loss in Phase 2.
Maridebart Cafraglutide (MariTide)
Medium EvidenceAmgen's once-monthly injectable GIP receptor antagonist and GLP-1 receptor agonist, showing up to 20% weight loss in phase 2 trials with a unique mechanism that blocks GIP while activating GLP-1.
Petrelintide
Medium EvidenceA long-acting amylin analog in late-stage clinical development for chronic weight management, designed to deliver double-digit weight loss with a tolerability profile comparable to placebo.
Semaglutide
High EvidenceA GLP-1 receptor agonist FDA-approved for type 2 diabetes and chronic weight management.