Guide · Updated November 2026

Amycretin vs Tirzepatide: The Next-Gen GLP-1/Amylin Drug

Amycretin (now also listed under the name zenagamtide in trial records) is Novo Nordisk's investigational GLP-1/amylin co-agonist (a dual agonist, not a triple). It produced 22.0% weight loss at 36 weeks on its 20 mg dose in a 125-person phase 1b/2a trial (Lancet, 2025). Tirzepatide reached 20.9% on 15 mg over 72 weeks in SURMOUNT-1 (NEJM, 2022). Tirzepatide (sold as Mounjaro and Zepbound) is FDA-approved and available now, with Zepbound KwikPen at $299 to $449 a month self-pay as of Nov 4, 2026 (Lilly). Amycretin's phase 3 AMAZE program began in 2026, and the first trial lists an estimated primary completion date of June 2029 (ClinicalTrials.gov).

Novo Nordisk needs a winner. Tirzepatide beats its own semaglutide (Wegovy, Ozempic) on weight loss, and the head-to-head SURMOUNT-5 trial confirmed it: tirzepatide produced 20.2% weight loss versus semaglutide’s 13.7% at maximum tolerated doses over 72 weeks (NEJM, 2025). So Novo Nordisk built something different. Amycretin does not just tweak the GLP-1 receptor. It combines GLP-1 activity with amylin receptor activation in a single molecule, targeting appetite through a pathway that tirzepatide does not touch.

The question for anyone following the amycretin vs tirzepatide comparison: does a new mechanism actually translate into better results, or is this just a corporate arms race?

How These Drugs Work (Different Mechanisms)

Understanding the mechanism matters here because these two drugs take genuinely different approaches to weight loss.

Tirzepatide is a dual GLP-1/GIP receptor agonist. It activates both the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. GLP-1 slows gastric emptying and reduces appetite. GIP appears to enhance fat metabolism and may improve how the body handles insulin. In the SURMOUNT-1 trial, the 15 mg dose produced 20.9% average weight loss over 72 weeks, among the largest results of any approved obesity drug.

Amycretin takes a different path. Instead of pairing GLP-1 with GIP, Novo Nordisk paired GLP-1 with amylin receptor activation. Amylin is a hormone your pancreas releases alongside insulin after meals. It signals to the brainstem that you are full, slows stomach emptying, and suppresses glucagon (which raises blood sugar). By combining GLP-1 and amylin signaling in one molecule, amycretin hits appetite control from two distinct brain pathways.

The distinction matters because GIP (tirzepatide’s second target) and amylin (amycretin’s second target) do fundamentally different things. GIP works more on metabolic efficiency. Amylin works more on satiety signaling in the brain. Early data hints that amycretin may produce weight loss faster, though only phase 3 data can confirm that.

For context on how the current generation of GLP-1 medications actually works for weight loss, that guide covers the basics.

Amycretin vs Tirzepatide: Weight Loss Data

Here is where things get interesting, and where you need to be careful about comparing numbers across different trials.

Tirzepatide (SURMOUNT-1)

The gold standard data comes from SURMOUNT-1 (NEJM, 2022), which enrolled 2,539 adults with obesity or overweight and no diabetes for 72 weeks. These are the intention-to-treat results:

At the 15 mg dose, 91% of participants lost at least 5% of their body weight, and 57% lost 20% or more. People who stayed on the 15 mg dose for the full trial averaged about 22.5%, which is the figure you often see quoted. The SURMOUNT-5 head-to-head trial later showed tirzepatide beat semaglutide: 20.2% vs 13.7% weight loss, which Lilly described as 47% greater relative weight loss (Pharmacy Times).

Amycretin (Phase 1b/2a)

Amycretin’s injectable phase 1b/2a trial showed 22.0% weight loss at 36 weeks on 20 mg, and 24.3% on the top 60 mg dose (Lancet, 2025). That is roughly the weight loss tirzepatide reached in 72 weeks, in half the time.

Now the caveats. This was a single-site trial with 125 randomized participants (101 on amycretin), and the authors reported that a large number of participants withdrew. Early-phase trials are smaller and shorter, and the patient populations differ. We do not know whether amycretin’s weight loss curve continues climbing past 36 weeks or plateaus. We also do not know how the side effect profile looks at scale. Every obesity drug looks better in phase 2 than it does once tens of thousands of real patients start using it.

But the trajectory is hard to ignore.

Head-to-Head Comparison

I have been on Mounjaro for over six months now, and my own results tracked close to the trial data. The idea that something could work even faster is genuinely compelling, but I have learned to wait for large-scale data before getting excited about phase 2 results.

The Pipeline Context

Amycretin is not the only next-gen obesity drug in development. It sits in a crowded pipeline, and understanding where it fits helps frame the amycretin vs tirzepatide comparison.

Retatrutide is the only triple agonist in this list, targeting GLP-1, GIP, and glucagon receptors simultaneously. Amycretin is a dual agonist. Retatrutide’s phase 2 trial showed 24.2% weight loss at 48 weeks on 12 mg (NEJM, 2023), and Lilly reported topline results from the phase 3 TRIUMPH-4 trial in December 2025: 28.7% at 68 weeks on 12 mg in adults with obesity and knee osteoarthritis. Those are the largest numbers reported so far. But it is not approved yet.

CagriSema matters here because it is also from Novo Nordisk and also targets amylin, but as a combination of two separate drugs (semaglutide plus cagrilintide) rather than a single molecule. In the REDEFINE 1 trial it produced 20.4% weight loss at 68 weeks versus 3.0% on placebo (NEJM, 2025). Amycretin’s advantage is that it combines both activities in one compound, which could mean simpler dosing and manufacturing.

For anyone looking at what is available right now, see our breakdown of oral vs injectable GLP-1 options or check the provider directory for current pricing on tirzepatide and semaglutide.

Side Effects: What We Know So Far

Tirzepatide’s side effect profile is well documented from large phase 3 trials. Amycretin’s is not.

Tirzepatide (Zepbound Label, Pooled Trials)

These rates come from the Zepbound prescribing information, which pools two placebo-controlled weight trials (5 mg, 10 mg and 15 mg doses):

The label also carries a boxed warning about thyroid C-cell tumors and says not to use tirzepatide if you or a family member has had medullary thyroid carcinoma or MEN 2. In the SURMOUNT-5 head-to-head, 6.1% on tirzepatide and 8.0% on semaglutide stopped treatment because of side effects (Pharmacy Times). For practical tips on handling these, see our guide on managing nausea on Mounjaro.

Amycretin (Early-Phase Data)

The Lancet paper reported that the most common side effects with amycretin were gastrointestinal, mostly mild to moderate, and that the safety profile was consistent with GLP-1 and amylin agonists. It also noted a high frequency of GI events. These rates come from a small trial, so they are less reliable than tirzepatide’s phase 3 data.

The amylin component adds a theoretical concern. Amylin-based drugs like pramlintide (Symlin, approved for diabetes) are known to cause nausea, especially early in treatment. Whether combining amylin activation with GLP-1 in a single molecule changes the side effect dynamic is something phase 3 trials will need to answer.

If you are currently managing GLP-1 side effects, the strategies that work for tirzepatide and semaglutide (slow titration, smaller meals, staying hydrated) would likely apply to amycretin as well.

Body Composition: The Real Question

Weight loss percentages grab headlines, but what matters more is what kind of weight you lose. Losing muscle along with fat is the central concern with every obesity drug, and it is something I track closely with DEXA scans.

What We Know About Tirzepatide

In the SURMOUNT-1 DXA substudy of 160 participants, about 25% of total weight lost on tirzepatide was lean mass and about 75% was fat (Diabetes, Obesity and Metabolism, 2025). Fat mass fell 33.9% while lean mass fell 10.9%. The proportion of lean mass in the body actually improved, so body composition got better even though some lean tissue was lost.

That is still a real concern. I have written extensively about muscle preservation strategies on GLP-1s and why resistance training is non-negotiable.

What We Know About Amycretin

Almost nothing, yet. Early-phase trials rarely include detailed body composition data from DEXA scans. We do not know whether amycretin’s faster weight loss comes at the expense of more muscle loss or whether the amylin pathway somehow preserves lean mass better.

This is one of the biggest unanswered questions. If amycretin produces 22% weight loss in 36 weeks but the lean-to-fat ratio is worse than tirzepatide, that changes the calculus significantly. Until phase 3 body composition data is published, anyone comparing these two drugs is missing a critical piece of the puzzle.

For anyone on a GLP-1 right now, the body composition guide and exercise protocol cover what actually helps preserve muscle during rapid weight loss.

Cost and Availability

This is where the comparison gets simple, because only one of these drugs exists as a product you can buy.

Tirzepatide: Available Now

If cost is the primary concern, our guide to the cheapest GLP-1 options online breaks down every pathway.

Amycretin: Not Available

Amycretin is in phase 3 clinical trials. It is not available for purchase anywhere. The first phase 3 trial, AMAZE 1, started in February 2026 and lists an estimated primary completion date of June 2029. Novo Nordisk has not announced an approval date, and approval before 2030 looks unlikely on that timeline.

You cannot buy amycretin from a compounding pharmacy either. It is an unapproved investigational drug, so there is no approved product or shortage listing that would allow compounding. Anything sold online as amycretin is not a legitimate product.

Who Should Care About Amycretin?

If you are starting GLP-1 treatment now: Tirzepatide is the stronger choice based on available data. It is FDA-approved, widely available, and has among the strongest weight loss results of any approved obesity medication. Waiting for amycretin means waiting several years with no guarantee it will outperform what already exists.

If you are on semaglutide and plateauing: Consider switching to tirzepatide rather than waiting for amycretin. In SURMOUNT-5, tirzepatide produced 20.2% weight loss versus 13.7% on semaglutide.

If you are in the industry or following the science: Amycretin is worth watching. The 22% at 36 weeks trajectory, if it holds in larger trials, would represent a meaningful advance. The GLP-1/amylin mechanism is different enough from GLP-1/GIP (tirzepatide) that it could offer advantages for specific patient populations.

Bottom Line

Amycretin’s early data is promising, but tirzepatide is the better choice for anyone seeking treatment today. Tirzepatide has more than four years of real-world use, FDA approval, and among the strongest weight loss data of any available medication (20.9% on 15 mg in SURMOUNT-1, and ahead of semaglutide in the SURMOUNT-5 head-to-head). Amycretin’s faster trajectory in phase 2 is noteworthy, but phase 2 results do not always survive larger trials. If you are ready to start, compare current GLP-1 providers and talk to a prescriber about tirzepatide.

FAQ

Is amycretin better than tirzepatide for weight loss?

It is too early to say. Amycretin showed 22.0% weight loss at 36 weeks on 20 mg in a 125-person phase 1b/2a trial, a faster pace than tirzepatide’s 20.9% at 72 weeks on 15 mg in SURMOUNT-1. But early-phase trials are small and short. We need phase 3 data before making direct efficacy comparisons.

When will amycretin be available?

Novo Nordisk has not announced an approval date. Phase 3 trials began in 2026, and the first one, AMAZE 1, lists an estimated primary completion date of June 2029. FDA review would follow, so approval before 2030 looks unlikely.

Is amycretin the same as CagriSema?

No. Both are from Novo Nordisk and both target amylin receptors, but they are different products. CagriSema is a combination injection of two separate drugs (semaglutide plus cagrilintide). Amycretin is a single molecule that activates both GLP-1 and amylin receptors. Amycretin is earlier in development.

Can I get amycretin from a compounding pharmacy?

No. Amycretin is an investigational drug with no FDA approval. Compounding pharmacies cannot legally produce it. It is only available through clinical trials.

What is a GLP-1/amylin co-agonist?

It is a single molecule designed to activate both the GLP-1 receptor and the amylin receptor simultaneously. GLP-1 reduces appetite and slows digestion. Amylin signals fullness to the brainstem and suppresses glucagon. Combining both in one drug targets weight loss through two distinct pathways.

Related

Guides:

• Cheapest GLP-1 Online · Insurance Coverage · Side Effects
• Mounjaro Dosage Guide · Oral vs Injectable · Exercise and Muscle
• Fat Loss vs Weight Loss · DEXA Scan Results · Mounjaro Plateau · Medicare Coverage · Wegovy Pill vs Injection

Provider Reviews: Ro · Hims · MEDVi · Found · Calibrate

Compare: All Providers · Best GLP-1 Programs · All Guides

What we checked

This AI-assisted public-source desk check reviewed the Lancet amycretin phase 1b/2a paper, the NEJM SURMOUNT-1, SURMOUNT-5, retatrutide phase 2 and REDEFINE 1 papers, the SURMOUNT-1 body composition analysis, ClinicalTrials.gov records for the AMAZE program, the Zepbound prescribing information on DailyMed, Lilly’s Zepbound and Mounjaro savings pages, Lilly’s TRIUMPH-4 announcement and FDA’s December 2024 tirzepatide shortage order on November 4, 2026. This is not a clinical review and it is not medical advice. Prices and policies change, so confirm them with the provider or your prescriber before you act.