New Medications

Amycretin: The New Oral Weight Loss Pill and What We Know So Far

GLP-1 Companion · 7 min read

The GLP-1 drug class has transformed weight management medicine over the past decade. But the next generation of obesity medications is already arriving — and one of the most anticipated is amycretin. Developed by Novo Nordisk (the company behind Ozempic and Wegovy), amycretin is an oral pill that combines two distinct mechanisms: GLP-1 receptor agonism and amylin receptor agonism.

While still in clinical development, early results from Phase 1 and Phase 2 trials have generated significant scientific and public interest, with weight loss numbers that rival or potentially exceed currently available injectable medications.

What Is Amycretin

Amycretin is a single oral molecule that simultaneously activates two hormone receptors:

• GLP-1 receptor: the same target as semaglutide (Ozempic/Wegovy) and liraglutide (Saxenda). GLP-1 receptor activation slows gastric emptying, reduces appetite, and improves blood sugar regulation.
• Amylin receptor: amylin is a hormone co-released with insulin from the pancreas. It works in the brain to reduce appetite and food intake, complementing GLP-1 effects through a distinct neural pathway.

By combining both mechanisms in a single oral pill, amycretin aims to achieve greater weight loss than GLP-1 monotherapy alone, while remaining convenient for patients who prefer not to inject.

Clinical Trial Results

Phase 1 Results (2024)

In a Phase 1 trial published in 2024, people with obesity taking oral amycretin for 12 weeks lost an average of approximately 13% of their body weight. This figure was striking because most oral medications (including Rybelsus, oral semaglutide) show significantly lower weight loss than their injectable counterparts due to poor oral bioavailability of peptide drugs. Amycretin appears to have been engineered for improved absorption.

Phase 2 Results

Phase 2 data extended the observation period and tested multiple doses. Participants taking the highest studied doses of amycretin for 36 weeks (approximately 9 months) lost an average of 22% of their body weight — a figure that exceeds the 15% seen with weekly injectable semaglutide (Wegovy) in the 68-week STEP trials and approaches the results seen with tirzepatide (Mounjaro/Zepbound).

Importantly, this weight loss was achieved with an oral pill taken daily, not a weekly injection. For many patients, that represents a significant quality-of-life improvement.

How Amycretin Compares to Existing GLP-1 Medications

• Ozempic/Wegovy (injectable semaglutide): ~15% average weight loss at 68 weeks. Weekly injection.
• Mounjaro/Zepbound (tirzepatide, GLP-1 + GIP dual agonist): ~20-22% average weight loss at 72 weeks. Weekly injection.
• Rybelsus (oral semaglutide): ~5% weight loss at 26 weeks. Daily pill, but significantly lower efficacy than injectable.
• Amycretin: ~22% weight loss at 36 weeks in Phase 2. Daily pill, not yet approved.

These figures suggest amycretin may be the first oral weight loss medication to match the efficacy of the best available injectable GLP-1 drugs — though direct head-to-head trials have not yet been conducted.

Side Effects Seen in Trials

The side effect profile of amycretin in trials has been broadly similar to other GLP-1 drugs:

• Nausea — the most commonly reported side effect, particularly during dose escalation
• Vomiting
• Decreased appetite (expected and desired)
• Constipation
• Diarrhea
• Headache

No unexpected or serious safety signals were reported in the Phase 1 or Phase 2 trials, but the studies involved relatively small numbers of participants for relatively short durations. Larger Phase 3 trials with thousands of participants are needed before a full safety profile can be established.

Where Amycretin Is in Development

As of mid-2026, amycretin is in Phase 3 clinical trials. Novo Nordisk has initiated large-scale trials studying amycretin across different patient populations, including people with obesity with and without type 2 diabetes. Phase 3 trials typically take 2-4 years to complete and analyze.

Assuming positive Phase 3 results, Novo Nordisk would then submit a New Drug Application (NDA) to the FDA. FDA review for a new molecular entity typically takes 12-18 months. A realistic estimate for potential U.S. approval — contingent on successful Phase 3 results — would be 2027-2028 at the earliest.

Why the Dual Mechanism Might Matter

The rationale for combining GLP-1 with amylin agonism is rooted in how the body's natural appetite regulation works. GLP-1 is released from the gut in response to eating and sends fullness signals. Amylin is released from the pancreas alongside insulin and sends complementary satiety signals through the hypothalamus and brainstem. Using both pathways simultaneously may produce stronger appetite suppression than either alone — without simply doubling the dose of one drug and its side effects.

This is the same logic behind tirzepatide's dual GLP-1 + GIP action, which outperformed semaglutide alone. Amycretin extends the principle by targeting amylin rather than GIP.

What About Patients Who Cannot Inject

One of the most significant potential advantages of amycretin, if approved, would be its oral formulation. Many patients who could benefit from GLP-1 therapy are reluctant or unable to self-inject. Needle phobia is common. Some medical conditions make injection sites difficult. An effective oral alternative could substantially expand access to this class of medication.

Currently, Rybelsus (oral semaglutide) fills this role but with considerably less efficacy than Wegovy or Mounjaro. If amycretin fulfills the promise of its early trials, it would be the first oral option matching injectable-level weight loss.

Will Amycretin Be Covered by Insurance

This is an open question. Insurance coverage for GLP-1 weight loss medications has been inconsistent even for FDA-approved drugs like Wegovy. Coverage decisions depend on the drug's approval indication, the payer, and the political landscape around obesity medication coverage. It is too early to speculate on how amycretin would be covered if approved.

How to Follow Amycretin Development

If you want to stay informed about amycretin's clinical progress, you can:

• Follow ClinicalTrials.gov for registered amycretin trial updates
• Watch for Novo Nordisk press releases announcing Phase 3 readouts
• Monitor FDA announcements for New Drug Application submissions
• Follow established endocrinology and obesity medicine journals for peer-reviewed publications

The Bottom Line

Amycretin is one of the most promising drugs in the obesity medicine pipeline. Its early clinical data showing ~22% weight loss in an oral formulation would, if confirmed in Phase 3 trials, represent a significant advance — the first oral medication to rival the efficacy of the best available injectable GLP-1 drugs. It is not available yet, and years of additional study are needed before it could reach patients. But for anyone following the future of GLP-1 medicine, amycretin is a name worth knowing.

Sources

• Novo Nordisk: Amycretin Phase 1 Results — NEJM 2024
• ClinicalTrials.gov — Amycretin Phase 3 Study