Amycretin phase 2 in type 2 diabetes: 14.5% weight loss with no plateau at 36 weeks

TL;DR

Novo Nordisk's amycretin - a single molecule that agonises both GLP-1 and amylin receptors simultaneously - produced up to 14.5% weight loss and HbA1c reduction of up to 1.8% at 36 weeks in a Phase 2 trial of 448 type 2 diabetes patients. 89.1% achieved HbA1c below 7% on the subcutaneous formulation. Weight loss had not plateaued at 36 weeks. Phase 3 in type 2 diabetes is launching in 2026.

Novo Nordisk has two horses in the next-generation obesity and diabetes race. CagriSema combines semaglutide with a separate amylin analogue (cagrilintide) in a co-injection. Amycretin takes a different engineering approach: it merges the GLP-1 and amylin actions into a single molecule. The Phase 2 results for amycretin in type 2 diabetes, published in late 2025, are the strongest data yet for this approach.

What amycretin is and why amylin matters

Amylin is a hormone co-secreted with insulin by the pancreas in response to meals. Like GLP-1, it suppresses appetite, slows gastric emptying, and reduces glucagon. Unlike GLP-1, amylin acts primarily through receptors in the brain rather than the gut - meaning the two hormones approach appetite suppression from complementary angles. Amylin also has effects on glucose regulation that are distinct from the insulin-sensitisation pathway that GLP-1 influences.

People with type 2 diabetes and obesity have impaired secretion of both GLP-1 and amylin. Replacing both simultaneously - which is what amycretin does in a single injection - targets the deficiency more completely than either hormone alone. The hypothesis driving amycretin development is that dual GLP-1 and amylin agonism will produce greater and more durable weight loss and glucose control than GLP-1 alone - just as dual GLP-1 and GIP agonism (tirzepatide) has outperformed GLP-1 mono-agonism (semaglutide) in head-to-head trials.

The Phase 2 trial: who was enrolled and what was tested

The Phase 2 trial enrolled 448 adults with type 2 diabetes inadequately controlled on metformin (some also using SGLT2 inhibitors - about 40% of participants). Two formulations were tested in parallel:

• Subcutaneous (injectable) amycretin: baseline HbA1c 7.8%, baseline weight approximately 99.2 kg
• Oral amycretin tablet: baseline HbA1c 8.0%, baseline weight approximately 101.1 kg

The primary endpoint was HbA1c reduction at 36 weeks. Secondary endpoints included weight loss percentage and proportion of patients achieving glucose control targets.

The results: exceptional glycaemic control and weight loss

Subcutaneous amycretin (36 weeks)

• HbA1c reduction: up to 1.8% (dose-dependent) vs 0.2% reduction in placebo
• Proportion achieving HbA1c below 7.0%: 89.1%
• Proportion achieving HbA1c of 6.5% or lower: 76.2%
• Weight loss: up to 14.5%
• Placebo weight loss: 2.6%

Oral amycretin (36 weeks)

• HbA1c reduction: up to 1.5% vs 0.4% in placebo
• Proportion achieving HbA1c below 7.0%: 77.6%
• Proportion achieving HbA1c of 6.5% or lower: 62.6%
• Weight loss: up to 10.1%
• Placebo weight loss: 2.5%

The most important single finding across both formulations: weight loss had not plateaued at 36 weeks. The curve was still descending. This is the same plateau-resistance pattern that made the VK2735 oral data exciting - and it suggests amycretin's dual-hormone mechanism may produce a more sustained weight loss response than mono-agonists, which tend to plateau around weeks 52-68.

How amycretin compares to the competition

At 36 weeks, 14.5% weight loss on subcutaneous amycretin is ahead of what tirzepatide (Mounjaro, Zepbound) produces at the same timepoint in type 2 diabetes trials - typically 8-12% at 36 weeks. However, tirzepatide eventually reaches 15-22% at 72-80 weeks. Whether amycretin will exceed tirzepatide at the same treatment duration is the question Phase 3 will answer.

For comparison, semaglutide (Ozempic) in the SOUL trial at 104 weeks produced approximately 4.2 kg weight loss in high-risk diabetics - far less, but in a different population and at a lower dose than the 2.4 mg Wegovy dose. Amycretin's 14.5% at 36 weeks - roughly 14.4 kg off a 99 kg baseline - is a substantially stronger signal.

The oral formulation: a different kind of pill

The oral amycretin result - 10.1% weight loss at 36 weeks - is particularly notable because this is a peptide-based drug in pill form, not a small molecule like Foundayo. Novo Nordisk developed proprietary technology to enable oral delivery of this combined peptide. The 10.1% oral result surpasses Foundayo's approximately 7-9% over a similar period, though direct comparisons across trials are methodologically unreliable. If Phase 3 confirms similar efficacy, oral amycretin would represent a step change in what oral GLP-1 therapy can achieve.

What this means for people on current GLP-1 medications

Amycretin is not yet approved and will not be commercially available before 2028 at the earliest based on Phase 3 timelines. If you are currently on semaglutide or tirzepatide - injectable or oral - amycretin is not a reason to change your current treatment. What matters now is supporting the nutritional status your current medication is affecting.

All GLP-1 and amylin-based therapies share the same appetite-suppression mechanism that drives nutrient deficiency risk. Reduced food intake on any of these medications - including future dual agonists like amycretin - creates documented gaps in vitamin B12, vitamin D, iron, magnesium, and zinc. Those gaps exist regardless of which specific molecule is producing the appetite suppression. GLP-1 Shield addresses the nutrient deficiency risks that the entire class of GLP-1 medications creates.

Frequently asked questions

What is amycretin and how does it differ from Ozempic?

Amycretin is a single molecule that activates both GLP-1 and amylin receptors simultaneously. Ozempic (semaglutide) activates only GLP-1 receptors. Amylin acts through brain receptors to suppress appetite and slow gastric emptying through a complementary pathway to GLP-1. By combining both mechanisms in one molecule, amycretin aims to produce greater weight loss and glucose control than semaglutide alone - a strategy similar to how tirzepatide outperforms semaglutide by adding GIP receptor agonism.

When will amycretin be available?

Phase 3 trials in type 2 diabetes are launching in 2026. Based on standard Phase 3 timelines and regulatory review, commercial availability is realistically 2028-2029 at the earliest. A separate Phase 3 program for obesity (without diabetes) is also expected to begin. The oral formulation and subcutaneous formulation are being developed in parallel.

How does amycretin compare to tirzepatide (Mounjaro, Zepbound)?

Phase 2 results for amycretin show 14.5% weight loss at 36 weeks without plateau, which is ahead of tirzepatide's typical result at the same timepoint. However, tirzepatide Phase 3 trials in obesity show 15-22% weight loss at 72-80 weeks. Whether amycretin can sustain its trajectory and match or exceed tirzepatide over longer periods is the critical Phase 3 question. The mechanisms are different: tirzepatide uses GLP-1 and GIP, amycretin uses GLP-1 and amylin.

Do people on amycretin still need vitamin supplements?

Based on what we know about GLP-1 medications generally, yes. All GLP-1 and amylin-based therapies suppress appetite and reduce food intake, creating the same nutrient deficiency risks documented across the class - particularly for vitamin B12, vitamin D, iron, and magnesium. There is no reason to expect amycretin to be different. GLP-1-specific supplementation remains relevant regardless of which molecule is being used.