Zenagamtide, formerly known as Amycretin, is one of Novo Nordisk’s most advanced next-generation obesity drugs. Unlike semaglutide, which activates the GLP-1 receptor, zenagamtide is a single peptide designed to activate both GLP-1 and amylin receptors.
The drug is also unusual because Novo Nordisk is developing it in two forms: a once-daily oral formulation and a once-weekly subcutaneous injection.
Early studies generated striking weight-loss numbers. Oral zenagamtide produced up to 13.1% mean weight loss after 12 weeks in an early obesity trial, while a once-weekly injectable regimen reached an estimated 24.3% weight reduction at 36 weeks at the highest dose studied.
Those figures are not directly comparable, however. The studies involved different treatment durations, doses, participant groups, and statistical analyses.
A later Phase 2 trial in people with type 2 diabetes provides another useful comparison. At week 36, the largest reported reductions were about 14.5–14.6% with injectable zenagamtide and 10.1% with oral zenagamtide, versus roughly 2.5% weight loss with the corresponding placebo groups.
The development program has since moved significantly forward. Novo Nordisk confirmed that its AMAZE Phase 3 obesity program was initiated in the first quarter of 2026, with multiple trials planned across obesity, type 2 diabetes, obstructive sleep apnea, knee osteoarthritis and other obesity-related complications. A dedicated Phase 3 trial, AMAZE 9, is designed to evaluate oral zenagamtide.
As of September 28, 2026, zenagamtide remains investigational and is not an approved obesity or diabetes medicine.
Medical notice: Zenagamtide is an experimental medicine undergoing clinical trials. The findings below do not establish that it is safe or effective for routine treatment. This article is educational and is not medical advice.
What Is Zenagamtide (Amycretin)?
Zenagamtide is the new name used by Novo Nordisk for the investigational molecule previously widely reported as Amycretin.
It is a unimolecular peptide agonist, meaning a single engineered molecule is designed to activate more than one hormonal pathway.
In this case, those pathways are:
- the GLP-1 receptor
- the amylin receptor system
Novo Nordisk is investigating zenagamtide for adults with overweight or obesity and separately for people with type 2 diabetes. Both oral and subcutaneous formulations are in development.
This dual-formulation approach could eventually become important if the drug reaches the market. Some patients may value the convenience of a tablet, while others may prefer a once-weekly injection over remembering a pill every day.
Whether both formulations ultimately receive regulatory approval remains unknown.
How Does Zenagamtide Work?
Zenagamtide combines two biological approaches that have independently attracted substantial attention in metabolic medicine.
GLP-1 activity
GLP-1 is a hormone released after eating. Activating GLP-1 receptors can affect appetite, food intake, insulin secretion, glucagon production and gastric emptying.
Drugs such as semaglutide already demonstrate that GLP-1 receptor activation can produce clinically meaningful weight loss and improve blood glucose.
Amylin activity
Amylin is normally secreted by pancreatic beta cells alongside insulin.
It contributes to meal-related satiety, influences glucagon secretion and helps regulate how quickly nutrients move through the stomach. Amylin signaling also acts on brain regions involved in food intake.
Zenagamtide attempts to place GLP-1 and amylin activity into one molecule rather than administering separate drugs.
Novo Nordisk describes the two pathways as complementary, with the aim of producing strong appetite and metabolic effects while keeping administration relatively simple.
That design distinguishes zenagamtide from CagriSema. CagriSema combines two separate molecules—cagrilintide and semaglutide—whereas zenagamtide is itself one engineered peptide with activity across the two receptor systems.
Zenagamtide Oral vs Injectable Results at a Glance
The available evidence comes from several different studies, so the results need to be separated carefully.
| Study population | Formulation | Dosing | Duration | Largest reported mean weight change |
|---|---|---|---|---|
| Overweight/obesity | Oral | Once daily | 12 weeks | -13.1% |
| Overweight/obesity | Injectable | Once weekly, 60 mg escalation cohort | 36 weeks | -24.3% |
| Overweight/obesity | Injectable | Once weekly, 20 mg | 36 weeks | -22.0% |
| Type 2 diabetes | Oral | Once daily, up to 50 mg studied | 36 weeks | -10.1% |
| Type 2 diabetes | Injectable | Once weekly, 40 mg | 36 weeks | about -14.5% to -14.6% |
The oral 13.1% and injectable 24.3% obesity numbers did not come from a single head-to-head trial of equivalent doses and treatment periods. They therefore should not be interpreted as proof that injections cause almost twice as much weight loss.
The Phase 2 diabetes study offers a more closely aligned look at the two routes, although treatment groups and doses still differed.
Oral Zenagamtide Results in Obesity
The first-in-human oral zenagamtide study enrolled 144 people across several trial components.
The key weight-loss portion used 12 weeks of treatment with escalating oral doses. Participants receiving the highest oral regimen—two 50 mg tablets taken as a single daily dose—experienced mean weight reduction of approximately 13.1% at week 12, compared with around 1.2% for placebo.
The weight trajectory was notable because reductions continued throughout the 12-week observation period rather than clearly flattening.
Novo Nordisk’s 2024 Capital Markets Day materials showed mean weight change in the highest-dose oral group progressing from roughly:
- -4.8% at week 4
- -8.1% at week 8
- -13.1% at week 12
The corresponding placebo result at week 12 was approximately -1.1% in that presentation.
The study was small and early stage, so it was primarily intended to examine safety, tolerability and pharmacokinetics—not to provide the definitive estimate of long-term weight loss expected from an approved dose.
That limitation matters.
A 12-week study cannot tell researchers whether weight loss continues for 40, 60 or 80 weeks, whether patients regain weight, or how many people tolerate full-dose treatment over a year.
Phase 3 is designed to answer those larger questions.
Injectable Zenagamtide Results in Obesity
The injectable development program produced even larger early weight reductions.
A Phase 1b/2a randomized controlled study enrolled 125 people with overweight or obesity, with 101 assigned to zenagamtide and 24 to placebo across several trial components.
Participants received once-weekly subcutaneous treatment with escalating doses.
Published results reported the following estimated mean weight changes:
| Injectable regimen | Treatment period | Zenagamtide | Placebo |
|---|---|---|---|
| 1.25 mg | 20 weeks | -9.7% | +2.0% |
| 5 mg | 28 weeks | -16.2% | +2.3% |
| 20 mg | 36 weeks | -22.0% | +1.9% |
| Escalation up to 60 mg | 36 weeks | -24.3% | -1.1% |
The 24.3% figure received significant attention because it approached the magnitude of weight loss sometimes associated with bariatric procedures or the strongest pharmacological obesity therapies.
But several qualifications are important.
First, this was still an early-stage study with relatively few people in each dose group.
Second, the highest-dose group did not spend the full 36 weeks at 60 mg. Treatment involved dose escalation.
Third, the statistical result reflects an estimate generated from the trial analysis rather than a promise that an individual taking zenagamtide would lose 24.3% of body weight.
Finally, early studies often enroll carefully selected participants under intensive research conditions. Phase 3 trials provide a much stronger test of whether efficacy can be reproduced across larger populations.
Oral vs Injectable Results in Type 2 Diabetes
Novo Nordisk later evaluated oral and injectable zenagamtide in a Phase 2 program involving 448 adults with type 2 diabetes inadequately controlled with metformin, with or without an SGLT2 inhibitor.
The study included six weekly injectable doses ranging from 0.4 mg to 40 mg and three once-daily oral doses: 6 mg, 25 mg and 50 mg. Treatment lasted up to 36 weeks.
This trial measured both blood-glucose control and body weight.
Injectable results
From a mean baseline HbA1c of 7.8%, injectable zenagamtide produced HbA1c reductions of up to approximately 1.8 percentage points.
Up to 89.1% of participants reached HbA1c below 7%.
Weight loss reached approximately 14.5–14.6% at week 36 in the highest-dose injectable group, versus roughly 2.1% to 2.6% with placebo depending on the analysis reported.
Oral results
With oral zenagamtide, HbA1c fell by up to approximately 1.5 percentage points from a mean baseline of 8.0%.
Around 77.6% of participants achieved HbA1c below 7%.
Maximum reported mean weight loss was 10.1%, compared with approximately 2.5% with oral placebo.
Novo Nordisk reported that there was no apparent weight-loss plateau at week 36 for the higher-dose groups with either administration route.
That observation suggests longer treatment might produce additional weight reduction, but only longer controlled trials can establish whether this actually occurs.
Zenagamtide Side Effects: What Have Trials Found?
The main side-effect signal seen so far has been gastrointestinal, broadly consistent with what researchers often observe when stimulating GLP-1 and amylin pathways.
Commonly reported problems have included:
- nausea
- vomiting
- diarrhea
- other gastrointestinal symptoms
- decreased appetite
The frequency and severity have varied by dose and trial.
Oral Zenagamtide Side Effects
The first-in-human oral study provides the most detailed early safety dataset.
Among all 144 participants exposed across the study’s parts, 89 participants, or 62%, reported treatment-emergent adverse events.
Researchers recorded 364 treatment-emergent adverse events. All were described as mild or moderate, and adverse-event frequency increased with dose.
Gastrointestinal problems accounted for 180 of the 364 recorded events. Among the 89 participants who experienced any treatment-emergent event, 72 had a gastrointestinal event.
No deaths were reported.
Published analyses have highlighted nausea and vomiting in particular at higher oral doses.
These numbers require cautious interpretation because the study was designed around ascending doses. Early dose-finding studies deliberately test different exposure levels to determine how much drug people can tolerate.
The eventual Phase 3 dosing schedule may therefore produce a different adverse-event profile.
Injectable Zenagamtide Side Effects
In the 125-participant injectable obesity study, the most frequent treatment-emergent adverse events were also gastrointestinal.
Reported symptoms included nausea, vomiting and diarrhea, along with decreased appetite. Most adverse events were mild to moderate and generally resolved by the end of the study.
One important feature of this study was participant withdrawal.
Approximately 33% of participants withdrew, but the published report noted that a large proportion of these discontinuations were for reasons unrelated to treatment-emergent adverse events. The Lancet report said 59% of withdrawals were unrelated to adverse events, including withdrawal of consent and recreational drug use.
The later Phase 2 diabetes trial also reported gastrointestinal adverse events as the most common category for both oral and injectable zenagamtide. Novo Nordisk described the majority as mild to moderate and said the overall safety profile was consistent with other incretin- and amylin-based treatments.
Phase 3 will provide a far more useful estimate of discontinuation rates and less-common adverse events.
Did Injectable Zenagamtide Work Better Than Oral Zenagamtide?
The simple answer is that injectable zenagamtide has produced the larger weight-loss percentages reported so far, but the available evidence does not support a clean “injection beats pill” conclusion.
The most dramatic obesity comparison is 24.3% weight loss with injectable zenagamtide at 36 weeks versus 13.1% with oral zenagamtide at 12 weeks.
But 36 weeks is three times longer than 12 weeks.
Dose escalation also differed.
The participants were enrolled in separate studies rather than randomized between oral and injectable treatment within one definitive head-to-head obesity trial.
The type 2 diabetes study is somewhat more informative because both routes were studied over 36 weeks. There, maximum weight loss was approximately 14.5% with weekly injectable zenagamtide and 10.1% with daily oral treatment.
Even that comparison does not establish that one route is intrinsically superior. Exposure, dose selection and tolerability may all affect outcomes.
Phase 3 should clarify how much efficacy Novo Nordisk can maintain with dosing regimens suitable for long-term clinical use.
There is also a convenience trade-off.
An oral medicine avoids needles but requires daily administration. The injectable formulation is being developed for once-weekly dosing.
For some patients, one weekly injection could actually be easier than remembering a tablet seven days a week. Others strongly prefer oral treatment.
That makes the existence of both formulations clinically interesting even if their final efficacy differs.
Zenagamtide Phase 3 Progress: The AMAZE Program
Zenagamtide has now progressed well beyond its initial Amycretin proof-of-concept studies.
Novo Nordisk confirmed that the AMAZE Phase 3 program in obesity was initiated during the first quarter of 2026.
The program is broader than a single weight-loss trial.
Novo Nordisk’s Q2 2026 investor presentation listed several selected Phase 3 studies.
AMAZE 1
AMAZE 1 is designed to evaluate weight loss in people with obesity.
The trial runs for 84 weeks against placebo and includes an additional 52-week extension phase. Weight loss is the primary endpoint.
This is likely to provide one of the clearest answers about how durable zenagamtide’s weight-loss effect is over a much longer period than the original 36-week study.
AMAZE 2
AMAZE 2 examines weight reduction in a population with type 2 diabetes.
Treatment is planned for 84 weeks against placebo, with weight loss as the primary endpoint.
AMAZE 3 and AMAZE 4
These studies extend zenagamtide research into obstructive sleep apnea, an obesity-related condition increasingly targeted by weight-management therapies.
AMAZE 3 runs for 80 weeks and includes co-primary endpoints related to weight loss and apnea-hypopnea index.
Novo Nordisk has also said AMAZE 4 was initiated in people with obesity and sleep apnea.
AMAZE 5 and AMAZE 6
AMAZE 5 evaluates people with obesity and knee osteoarthritis.
Its co-primary measurements include weight loss and the WOMAC osteoarthritis assessment.
AMAZE 6 is another study in the obesity and knee-osteoarthritis population.
AMAZE 9: Oral Zenagamtide
For readers specifically tracking an Amycretin pill, AMAZE 9 is particularly important.
Novo Nordisk lists AMAZE 9 as a 76-week Phase 3 oral zenagamtide study against placebo, with weight loss as the primary endpoint.
This trial should provide a much more reliable measure of the oral formulation’s long-term efficacy than the original 12-week Phase 1 study.
Novo Nordisk is therefore not treating the oral drug as a secondary experiment. Oral zenagamtide is incorporated directly into its late-stage obesity development strategy.
HF Polaris
Novo Nordisk has also listed HF Polaris, a heart-failure study of zenagamtide added to standard care.
The trial can extend up to approximately 165 weeks, with time to a first composite heart-failure endpoint as the primary measure.
This illustrates how obesity-drug development is increasingly moving beyond kilograms lost toward disease outcomes that matter directly to patients.
What About Phase 3 for Type 2 Diabetes?
The type 2 diabetes program is called AMBITION.
After positive Phase 2 findings, Novo Nordisk said zenagamtide would move into Phase 3 development for adults with type 2 diabetes.
The company’s Q2 2026 materials described three selected studies:
| Trial | Design | Primary focus |
|---|---|---|
| AMBITION 1 | 44 weeks vs placebo | HbA1c |
| AMBITION 2 | 52 weeks, add-on to insulin | HbA1c |
| AMBITION 3 | 60-week head-to-head study vs semaglutide 1.0 mg | HbA1c |
AMBITION 3 is particularly noteworthy because it is planned as an active-comparator trial rather than placebo-only testing.
Novo Nordisk’s published program design includes zenagamtide doses up to 40 mg in late-stage development.
The company had indicated that AMBITION would begin in the second half of 2026. As of September 28, publicly available company materials clearly confirm the AMAZE obesity program’s initiation; the diabetes program remains one to monitor for updated individual trial-start confirmations.
Is Zenagamtide Approved?
No.
Zenagamtide remains an investigational medicine.
Neither the oral nor injectable formulation is currently approved as a weight-loss or diabetes treatment.
The drug must successfully complete Phase 3 trials and undergo regulatory review before it could be prescribed commercially.
A successful early trial does not guarantee approval.
Regulators need a much larger body of evidence covering efficacy, adverse events, treatment discontinuation, manufacturing, dosing and the overall balance between benefits and risks.
What Phase 3 Still Needs to Prove
Zenagamtide’s early efficacy makes it an important obesity candidate, but several questions remain unanswered.
1. What is the sustainable long-term weight loss?
The 24.3% injectable result was generated over 36 weeks in an early trial.
AMAZE studies running for approximately 76 to 84 weeks should provide a much better picture of long-term efficacy.
2. Can the highest doses be tolerated at scale?
Higher exposure produced greater weight reduction in early studies, but gastrointestinal adverse events also tended to rise with dose.
The clinically useful dose is not simply the one that produces the largest numerical weight reduction. It must also be tolerable enough for people to remain on treatment.
3. How competitive will the oral formulation be?
A 13.1% reduction over 12 weeks attracted substantial attention, but oral zenagamtide now needs to prove itself in a long Phase 3 setting.
AMAZE 9 will be especially important.
4. Are there meaningful differences between oral and injectable treatment?
The final choice may involve more than efficacy.
Administration frequency, tolerability, food or fasting instructions, manufacturing cost, patient preference and medication adherence could all influence the practical value of each formulation.
5. What happens to cardiovascular and other obesity-related outcomes?
Weight loss is valuable, but regulators and clinicians are increasingly interested in effects on cardiovascular disease, heart failure, sleep apnea, mobility and metabolic complications.
Novo Nordisk’s broader AMAZE and HF Polaris strategy appears designed to explore some of those questions.
6. What happens after treatment stops?
Like other pharmacological obesity therapies, zenagamtide will eventually need data showing what happens when treatment is reduced, discontinued or maintained for multiple years.
Those answers are not available from the original early-phase studies.
Frequently Asked Questions About Zenagamtide
Is Zenagamtide the Same as Amycretin?
Yes. Zenagamtide is the name now used for the investigational medicine previously known as Amycretin. Novo Nordisk’s current clinical-development materials use zenagamtide, while older studies and news coverage frequently use Amycretin.
Is Zenagamtide a GLP-1 Drug?
Partly. Zenagamtide activates the GLP-1 receptor, but it also activates the amylin receptor system. This dual mechanism distinguishes it from medicines that act only through GLP-1.
Is Amycretin Available as a Pill?
An oral formulation is being developed, but it is not commercially available. Early trials used once-daily oral zenagamtide, and Novo Nordisk has included oral treatment in its Phase 3 AMAZE program.
How Much Weight Did Oral Amycretin Cause People to Lose?
The highest oral regimen in the first-in-human obesity study produced approximately 13.1% mean weight loss after 12 weeks, compared with roughly 1% for placebo. This was an early Phase 1 result and should not be interpreted as the final expected efficacy of an approved dose.
How Much Weight Did Injectable Zenagamtide Produce?
The largest early obesity result was approximately 24.3% mean weight loss after 36 weeks in the cohort that escalated to 60 mg, versus approximately 1.1% with placebo. A 20 mg regimen produced an estimated 22.0% reduction at week 36.
What Were Zenagamtide’s Results in Type 2 Diabetes?
In Phase 2, weekly injectable zenagamtide produced up to roughly 14.5–14.6% weight loss and an HbA1c reduction of up to approximately 1.8 percentage points. Daily oral treatment produced up to 10.1% weight loss and an HbA1c reduction of approximately 1.5 percentage points at week 36.
What Are the Main Zenagamtide Side Effects?
Gastrointestinal effects have been the main adverse-event category. Reported symptoms include nausea, vomiting and diarrhea, particularly during dose escalation and at higher doses. Most reported events in early trials were mild to moderate.
Is Oral Zenagamtide Safer Than the Injection?
There is not enough evidence to conclude that one route is safer overall.
Both formulations have produced gastrointestinal side effects. Differences in trial design, dose and exposure prevent a reliable safety ranking based on current evidence.
Is Zenagamtide in Phase 3?
Yes. Novo Nordisk initiated the AMAZE Phase 3 obesity program in the first quarter of 2026. The program includes multiple studies, and AMAZE 9 specifically evaluates oral zenagamtide.
What Is the Difference Between Zenagamtide and CagriSema?
Zenagamtide is a single engineered molecule with GLP-1 and amylin receptor activity.
CagriSema is a fixed-dose combination containing two separate components: the amylin analog cagrilintide and the GLP-1 receptor agonist semaglutide.
When Could Zenagamtide Become Available?
There is no confirmed approval or launch date.
Large Phase 3 trials must first be completed, analyzed and submitted to regulators. The timing of regulatory decisions will depend on the results and subsequent review process.
Are New Zenagamtide Results Expected at EASD 2026?
Novo Nordisk has listed zenagamtide among the amylin-related topics being discussed at the EASD 2026 meeting in Milan, running September 28 to October 2, 2026. A Novo Nordisk session focused partly on zenagamtide is scheduled for September 30. Because this article is updated on September 28, those presentations have not yet occurred and should not be treated as available results.
Conclusion
Zenagamtide, previously called Amycretin, has developed from an intriguing experimental obesity drug into a substantial Phase 3 program spanning oral and injectable treatment.
Early obesity studies showed unusually large weight reductions: up to 13.1% after 12 weeks with oral treatment and 24.3% after 36 weeks with once-weekly injectable treatment. The later type 2 diabetes Phase 2 program reported approximately 10.1% weight loss with oral zenagamtide and 14.5–14.6% with the injectable formulation at 36 weeks.
Those percentages make zenagamtide a closely watched candidate, but they should not be interpreted as a definitive oral-versus-injection contest. The obesity studies differed significantly in duration, dose and design.
Safety also remains central. Gastrointestinal effects—including nausea, vomiting and diarrhea—have been prominent, although most reported adverse events in the early studies were mild or moderate.
The biggest change is the scale of development.
Novo Nordisk’s AMAZE Phase 3 program is now underway, examining weight management as well as obesity-related conditions including sleep apnea and knee osteoarthritis. Oral zenagamtide has its own 76-week Phase 3 study, AMAZE 9, while the AMBITION program is designed to extend development in type 2 diabetes.
Phase 3 will determine whether zenagamtide can reproduce its early weight-loss results in thousands of participants while maintaining tolerability during longer treatment.
If it does, the ability to offer the same dual GLP-1/amylin concept as either a daily tablet or weekly injection could become one of zenagamtide’s most distinctive features.
For now, however, both formulations remain investigational.
Sources
Novo Nordisk, Q2 2026 Investor Presentation. Current primary source for the AMAZE and AMBITION Phase 3 program design, including AMAZE 1, 2, 3, 5 and 9, HF Polaris and selected diabetes trials.
Novo Nordisk, June 2026 ADA announcement. Primary source for the 36-week injectable Phase 2 results in type 2 diabetes and the planned move into Phase 3.
Novo Nordisk, November 2025 Phase 2 announcement. Primary source comparing oral and subcutaneous zenagamtide in adults with type 2 diabetes.
The Lancet / PubMed — subcutaneous Amycretin Phase 1b/2a trial. Peer-reviewed source reporting up to 24.3% estimated weight reduction at 36 weeks and gastrointestinal adverse events.
The Lancet / PubMed — first-in-human oral Amycretin trial. Peer-reviewed source for oral safety, tolerability, pharmacokinetics and the early 12-week obesity program.
Novo Nordisk Capital Markets Day 2024. Primary company source showing the 13.1% oral weight-loss result at week 12.
Novo Nordisk, January 2025. Primary source for the initial subcutaneous Amycretin obesity topline results.
Novo Nordisk, June 2025. Primary source announcing the decision to advance oral and subcutaneous Amycretin into Phase 3 weight-management development.
Novo Nordisk Q1 2026 results. Source confirming that the AMAZE Phase 3 program had been initiated.
Novo Nordisk EASD 2026 materials. Source for the September 2026 congress schedule and planned zenagamtide discussion.