Major Peptide Clinical Trial Results Expected 2026

2026 is loaded with high-stakes readouts. Four drugs — retatrutide, survodutide, orforglipron, and CagriSema — are reporting Phase 3 data that will shape the next generation of obesity and metabolic disease treatment. Here is what each trial program is testing, what we already know, and why the results matter.

Table of Contents

Why 2026 Is a Turning Point
Retatrutide: Seven Phase 3 Readouts on Deck
CagriSema: The Head-to-Head Everyone Is Watching
Orforglipron: The First Non-Peptide Oral GLP-1
Survodutide: Dual Agonism for Obesity and Liver Disease
Pemvidutide: Breakthrough Therapy for MASH
What These Trials Mean for Patients
2026 Trial Timeline at a Glance
FAQ
The Bottom Line
References

Why 2026 Is a Turning Point

The obesity drug pipeline has never been this full. As of early 2026, more than 157 clinical-stage assets spanning over 60 distinct mechanisms of action are working their way through development. But five programs stand out — not because they are theoretical, but because their Phase 3 data will land this year, and each one tests a different approach to weight loss and metabolic disease.

This year's readouts will answer specific questions that Phase 2 trials left open: Does triple agonism outperform dual agonism? Can an oral pill match an injection? Does adding an amylin analog on top of semaglutide produce meaningfully better results? And can a glucagon-GLP-1 dual agonist reverse liver fibrosis?

The financial stakes match the clinical ones. Late-stage GLP-1 candidates from Eli Lilly, Novo Nordisk, and other developers carry a combined net present value north of $68 billion. GlobalData projects retatrutide alone could reach $15.6 billion in annual sales by 2031.

Retatrutide: Seven Phase 3 Readouts on Deck

Retatrutide is Eli Lilly's triple-receptor agonist — a single molecule that activates GLP-1, GIP, and glucagon receptors simultaneously. The logic: GLP-1 and GIP suppress appetite and improve insulin secretion, while glucagon receptor activation increases energy expenditure and promotes fat oxidation in the liver.

What We Already Know

The first Phase 3 result dropped in late 2025. TRIUMPH-4, a 68-week trial in adults with obesity and knee osteoarthritis, reported average weight loss of up to 28.7% — roughly 71.2 pounds. That number surpassed every published result from tirzepatide trials and set a new high-water mark for pharmacological weight loss. The trial also met all primary and secondary endpoints, including pain reduction and improved physical function.

Beyond weight loss, retatrutide reduced non-HDL cholesterol, triglycerides, and high-sensitivity C-reactive protein (hsCRP). The highest dose lowered systolic blood pressure by 14.0 mmHg.

What is Coming in 2026

Seven additional TRIUMPH trials are expected to read out:

TRIUMPH-1 (estimated completion May 2026): 2,300 patients with obesity, testing 4 mg, 9 mg, and 12 mg doses
TRIUMPH-2 (estimated May 2026): 1,000 patients with type 2 diabetes and obesity, including a subset with obstructive sleep apnea
TRIUMPH-3 (estimated February 2026): Body weight change in obese individuals with established cardiovascular disease
Additional studies covering chronic low back pain, moderate-to-severe obstructive sleep apnea, cardiovascular and renal outcomes, and metabolic dysfunction-associated steatotic liver disease (MASLD)

These trials will determine whether the 28.7% weight loss seen in TRIUMPH-4 holds up across different patient populations and at different doses. The MASLD data is particularly anticipated — if retatrutide's glucagon component drives meaningful liver fat reduction, it could position the drug as both an obesity treatment and a liver disease therapy.

Lilly is targeting a 2027 regulatory submission if the readouts are positive.

CagriSema: The Head-to-Head Everyone Is Watching

CagriSema pairs two mechanisms in one injection: semaglutide (a GLP-1 receptor agonist) and cagrilintide (a long-acting amylin analog). The hypothesis is that dual appetite suppression — through both GLP-1 and amylin pathways — will outperform semaglutide alone.

Phase 3 Results Already In

REDEFINE 1 (3,417 adults with obesity, no diabetes): CagriSema achieved 20.4% average body weight reduction at 68 weeks versus 3.0% for placebo. Among participants who stayed on treatment for the full study duration, weight loss reached approximately 23%.

REDEFINE 2 (1,206 adults with type 2 diabetes): CagriSema produced 13.7% mean weight loss versus 3.4% for placebo. On the glycemic side, 73.5% of patients reached an HbA1c of 6.5% or below, compared to 15.9% on placebo.

These are strong numbers, but they fell short of the 25% target that some analysts had expected. Novo Nordisk's stock took a hit when the data was released, and questions remain about how CagriSema stacks up against tirzepatide.

The 2026 Showdowns

REIMAGINE 2 (announced February 2, 2026): CagriSema demonstrated superior HbA1c reduction and weight loss versus semaglutide alone across all tested doses at 68 weeks. This confirms the amylin component adds meaningful benefit on top of semaglutide in diabetes patients.

The head-to-head against Zepbound: Data from a direct comparison of CagriSema versus tirzepatide (Zepbound) in obesity is expected by the end of March 2026. This trial is arguably the single most important readout of the year. If CagriSema matches or beats tirzepatide, it validates Novo Nordisk's combination strategy. If it falls short, it hands Eli Lilly a significant competitive advantage.

Novo Nordisk filed CagriSema for U.S. FDA approval for weight management in December 2025. The expected approval timeline is late 2026 for obesity and 2026-2027 for type 2 diabetes.

Orforglipron: The First Non-Peptide Oral GLP-1

Orforglipron is not technically a peptide — it is a small molecule that activates the GLP-1 receptor. That distinction matters because small molecules can be manufactured as pills without the bioavailability challenges that plague oral peptide formulations. Orforglipron can be taken once daily at any time, with no restrictions on food or water intake.

Completed Phase 3 Data

Three Phase 3 trials have reported results:

ATTAIN-1 (obesity, reported August 2025): Topline data showed statistically significant weight loss. Full results were published in the New England Journal of Medicine in September 2025.
ATTAIN-2 (type 2 diabetes): The 36 mg dose reduced weight by 10.5% versus 2.2% with placebo.
ATTAIN-MAINTAIN: Participants who had been on injectable Wegovy or Zepbound maintained their weight loss after switching to oral orforglipron over 52 weeks. This is the first data showing that patients can transition from injections to a pill without regaining weight.

What is Left in 2026

ACHIEVE-4 (type 2 diabetes, final ongoing trial): Results expected in the first half of 2026. This trial should complete the regulatory package for the diabetes indication.

FDA Decision: Lilly has submitted a new drug application, and orforglipron received one of the FDA's new Commissioner's National Priority Vouchers. That designation could compress the review timeline to weeks rather than the standard 6-10 months. Self-pay pricing through LillyDirect will start at $149 for the lowest dose and up to $399 for higher doses.

Clarivate projects orforglipron sales of $16 billion by 2031. Analysts at Truist Securities think the combined Lilly obesity franchise (Mounjaro, Zepbound, and orforglipron) could reach $101 billion in peak sales.

The drug arrives in a market where Novo Nordisk's oral Wegovy (semaglutide 25 mg pill) has already launched. Oral Wegovy hit 50,000 weekly prescriptions in under three weeks after its December 2025 FDA approval. Orforglipron's advantage is convenience — no fasting window required, unlike oral semaglutide.

Survodutide: Dual Agonism for Obesity and Liver Disease

Survodutide targets both GLP-1 and glucagon receptors. Developed by Boehringer Ingelheim, it is being tested for obesity and for metabolic dysfunction-associated steatohepatitis (MASH), the advanced form of fatty liver disease.

Phase 2 Context

Survodutide produced 18.7% weight loss in Phase 2 obesity trials. The liver data was even more striking: in Phase 2 MASH studies, 47-62% of patients achieved MASH resolution versus 14% on placebo. These results earned survodutide FDA Breakthrough Therapy designation for MASH.

Phase 3 Timeline

Two global Phase 3 trials are running:

SYNCHRONIZE-1: Adults with obesity, without type 2 diabetes. 76-week treatment period.
SYNCHRONIZE-2: Adults with obesity and type 2 diabetes. Recruitment completed June 2024.

Both studies are expected to complete in the first half of 2026, with analyzed results available later in the year. If the data confirms what Phase 2 suggested, Boehringer Ingelheim would file for FDA approval with potential market entry in 2027.

Survodutide's dual profile — treating obesity and liver disease simultaneously — could carve out a distinct clinical niche. MASH affects an estimated 5% of U.S. adults and has limited treatment options. A drug that addresses both the metabolic driver (obesity) and the organ damage (liver fibrosis) would be genuinely differentiated.

Pemvidutide: Breakthrough Therapy for MASH

Pemvidutide is another GLP-1/glucagon dual agonist, developed by Altimmune, but with balanced 1:1 receptor activity — meaning it activates both receptors with roughly equal potency. Its primary development focus is MASH rather than obesity.

48-Week Phase 2b Results (IMPACT Trial)

In December 2025, Altimmune reported topline data from 212 patients with biopsy-confirmed MASH and fibrosis stages F2 or F3. The 1.8 mg dose produced 7.5% body weight loss at 48 weeks, with weight loss still accelerating between weeks 24 and 48 — no plateau in sight.

The trial met its primary endpoint of MASH resolution without worsening of fibrosis at 24 weeks. Tolerability was notable: treatment discontinuation due to adverse events occurred in only 0-1.2% of patients on pemvidutide versus 3.5% on placebo.

FDA Breakthrough Therapy Designation

On January 5, 2026, the FDA granted pemvidutide Breakthrough Therapy designation for MASH, expediting its development and review. Altimmune has completed its end-of-Phase 2 meeting with the FDA and aligned on parameters for a registrational Phase 3 trial, which will use biopsy-based endpoints over 52 weeks.

What These Trials Mean for Patients

The 2026 readouts are not just about which company's stock goes up. Each program addresses specific gaps in current treatment:

For obesity patients: Retatrutide could offer the most weight loss of any drug studied to date. Orforglipron offers a daily pill that works without food restrictions. CagriSema may provide an alternative for patients who do not respond optimally to GLP-1 alone.

For diabetes patients: The ACHIEVE-4 and REIMAGINE trials will expand the evidence base for using these agents in type 2 diabetes, potentially with glycemic benefits that rival or exceed current therapies.

For liver disease patients: Survodutide and pemvidutide target MASH directly. If their Phase 3 data confirms earlier results, they could become the first dual-agonist treatments approved for liver fibrosis — addressing a disease where resmetirom (Rezdiffra) is the only approved therapy.

For access: Orforglipron's oral formulation and CagriSema's filing for approval both signal a future where more patients can access these treatments. The TrumpRx pricing deal has already dropped Medicare prices for existing GLP-1s to $245, and oral options could drive costs down further.

2026 Trial Timeline at a Glance

Drug	Developer	Mechanism	Expected Readout	Key Question
Retatrutide	Eli Lilly	Triple (GLP-1/GIP/Glucagon)	Feb-May 2026 (7 trials)	Does 28.7% weight loss hold across populations?
CagriSema	Novo Nordisk	GLP-1 + Amylin	March 2026 (head-to-head)	Can it match tirzepatide?
Orforglipron	Eli Lilly	Oral GLP-1 (small molecule)	H1 2026 (ACHIEVE-4); FDA decision pending	First convenient oral GLP-1?
Survodutide	Boehringer Ingelheim	Dual GLP-1/Glucagon	H1-H2 2026	Does Phase 2 liver data translate to Phase 3?
Pemvidutide	Altimmune	Dual GLP-1/Glucagon (1:1)	Phase 3 initiation 2026	Can balanced dual agonism treat MASH safely?

FAQ

Which peptide trial result will have the biggest impact in 2026?

The CagriSema versus Zepbound head-to-head, expected by end of March 2026, will likely move markets and clinical practice the most. It is the first direct comparison between Novo Nordisk's and Eli Lilly's best obesity drugs. The retatrutide TRIUMPH program matters just as much clinically, but with seven separate readouts, the data will arrive in stages rather than as a single event.

When will retatrutide be available to patients?

If the TRIUMPH Phase 3 data is positive across all seven trials, Eli Lilly is targeting a 2027 regulatory submission. Approval would likely follow in late 2027 or 2028, assuming standard FDA review timelines.

Is orforglipron really a pill version of Ozempic?

Not exactly. Orforglipron is a small molecule, not a reformulated peptide. It activates the same GLP-1 receptor as semaglutide, but its chemical structure is completely different. The practical advantage is that it can be taken at any time of day without fasting, unlike Novo Nordisk's oral semaglutide (oral Wegovy), which requires a 30-minute fasting window.

What is the difference between survodutide and pemvidutide?

Both are GLP-1/glucagon dual agonists, but they differ in receptor balance and development strategy. Survodutide is developed by Boehringer Ingelheim for both obesity and MASH, with a clinical program that mirrors traditional obesity drug development. Pemvidutide, from Altimmune, has balanced 1:1 GLP-1/glucagon activity and is being developed primarily as a MASH therapy with weight loss as a secondary benefit.

How do these new drugs compare to existing options like semaglutide and tirzepatide?

In terms of weight loss, retatrutide's 28.7% appears to top tirzepatide's approximately 22.5% from the SURMOUNT trials. CagriSema's 20.4% is in the range of tirzepatide's results. Orforglipron's 10.5% is lower, but it offers the convenience of a daily pill. Direct comparisons are tricky because trial designs, patient populations, and treatment durations differ across programs.

The Bottom Line

The 2026 clinical trial calendar is packed with readouts that will define obesity and metabolic disease treatment for the next decade. Retatrutide is pushing weight loss into territory that was previously surgical. CagriSema is testing whether dual-pathway suppression can outmatch the current standard. Orforglipron is proving that GLP-1 therapy does not require a needle. And survodutide and pemvidutide may open new options for fatty liver disease.

None of these are guaranteed to succeed — Phase 3 trials produce disappointments regularly. But the diversity of mechanisms, formulations, and targets being tested in 2026 means that even partial success across these programs will significantly expand patient options within the next two to three years.

References

Eli Lilly. "Lilly's triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs." Press Release, December 2025.
Giblin MJ, et al. "Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials." Diabetes, Obesity and Metabolism, 2026. DOI.
Novo Nordisk. "Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity." NEJM, 2025. DOI.
Novo Nordisk. "CagriSema demonstrated superior HbA1c reduction in REIMAGINE 2 trial." Press Release, February 2026.
Eli Lilly. "Lilly's oral GLP-1, orforglipron, demonstrated statistically significant efficacy results." Press Release.
Wharton S, et al. "Baseline characteristics in the SYNCHRONIZE-2 randomized phase 3 trial of survodutide." Diabetes, Obesity and Metabolism, 2026. DOI.
Altimmune. "Pemvidutide Achieved Key Measures of Success at 48 Weeks in IMPACT Phase 2b MASH Trial." Press Release, December 2025.
Altimmune. "Altimmune Receives FDA Breakthrough Therapy Designation for Pemvidutide in MASH." Press Release, January 2026.
"Retatrutide -- A Game Changer in Obesity Pharmacotherapy." PMC, 2025. PMC12190491.
Boehringer Ingelheim. "Survodutide US FDA Breakthrough Therapy phase 3 trials." Company Page.