Peptides in Clinical Trials: What’s Coming in 2026–2027

By NorthPeptide Research Team · April 19, 2026

Why 2026–2027 Is a Pivotal Window for Peptide Research

Clinical trial pipelines move slowly — until they don’t. After years of incremental progress in GLP-1 pharmacology, the 2026–2027 window represents a convergence moment: multiple late-stage trials reporting simultaneously, a new generation of multi-receptor agonists demonstrating efficacy beyond what single-target drugs can achieve, and the first oral GLP-1 candidates clearing Phase 3 with meaningful results.

This article tracks the most significant peptides currently in late-stage trials, explains what each trial is designed to show, and frames what these findings mean for the broader research landscape.

Retatrutide — TRIUMPH Phase 3

Retatrutide (LY3437943, Eli Lilly) is the leading triple agonist in clinical development, targeting GLP-1, GIP, and glucagon receptors simultaneously. Phase 2 data published in the New England Journal of Medicine in 2023 showed up to 24.2% mean body weight reduction at 48 weeks — the highest ever reported for a once-weekly injectable at that time (PMID 37366364).

The TRIUMPH program is Lilly’s Phase 3 clinical trial suite for retatrutide, covering:

• TRIUMPH-1 — obesity without type 2 diabetes, evaluating 4 mg and 8 mg doses vs. placebo over 72 weeks
• TRIUMPH-2 — obesity with type 2 diabetes, assessing glycemic control alongside weight outcomes
• TRIUMPH-3 — cardiovascular outcomes in a high-risk population
• TRIUMPH-NASH — MASLD/MASH (metabolic liver disease), evaluating hepatic fat reduction and fibrosis resolution

What makes retatrutide’s glucagon receptor component particularly relevant is its hepatic fat-clearing mechanism. Glucagon directly stimulates fatty acid oxidation in liver cells — a property that positions retatrutide as potentially more effective for MASLD than GLP-1-only compounds. Phase 2 sub-analyses showed substantial reductions in liver fat fraction, supporting the liver-focused arm of the TRIUMPH program.

Survodutide — SYNCHRONIZE Phase 3

Survodutide (BI 456906, Boehringer Ingelheim / Zealand Pharma) is a dual GLP-1/glucagon receptor agonist — a different architecture than retatrutide but sharing the glucagon component. Phase 2 SYNCHRONIZE trial data presented at EASD 2023 showed up to 18.7% weight loss at 46 weeks, with particularly strong effects on liver fat in MASH-focused subgroups (PMID 37703890).

The Phase 3 SYNCHRONIZE program includes:

• SYNCHRONIZE-WEIGHT — obesity and overweight without diabetes
• SYNCHRONIZE-MASH — metabolic dysfunction-associated steatohepatitis, making survodutide one of the few peptides with a dedicated liver disease program
• SYNCHRONIZE-CVOT — cardiovascular outcomes study in patients with established CV disease

Survodutide’s Phase 3 MASH results are among the most closely watched in liver disease research. Phase 2 data showed MASH resolution in 83% of patients at the highest dose, with fibrosis improvement in 79% — numbers that, if replicated in Phase 3, would represent a significant breakthrough for a disease with very limited approved treatment options.

CagriSema — REDEFINE Program

CagriSema is a fixed-dose combination of cagrilintide (a long-acting amylin analog, Novo Nordisk) and semaglutide 2.4 mg — a dual-mechanism approach pairing GLP-1 receptor agonism with amylin receptor activation. Amylin is a pancreatic hormone that complements GLP-1 by suppressing glucagon, slowing gastric emptying, and reducing food intake through separate hypothalamic pathways.

The Phase 3 REDEFINE program results have generated significant interest:

• REDEFINE 1 (obesity, non-diabetic) — 22.7% mean body weight reduction at 68 weeks with cagrisema vs. 8.0% for placebo (PMID 38377450)
• REDEFINE 2 (type 2 diabetes) — 15.7% weight reduction, demonstrating strong efficacy even with the attenuated response typically seen in diabetic populations

The amylin component addresses a gap in pure GLP-1 therapy: amylin acts in the brainstem’s area postrema, a region distinct from the hypothalamic GLP-1 receptor targets. This means CagriSema recruits satiety circuits that semaglutide alone does not fully engage — which may explain the meaningfully higher weight loss percentages compared to semaglutide 2.4 mg as a standalone.

Elamipretide (SS-31) — Heart Failure and Barth Syndrome

Elamipretide, also known by its research designation SS-31 (Szeto-Schiller peptide-31) and the development code MTP-131, is a mitochondria-targeted tetrapeptide developed by Stealth BioTherapeutics (now Mitobridge/Astellas). Unlike the metabolic peptides described above, elamipretide works through an entirely different mechanism: it concentrates within the inner mitochondrial membrane, where it binds cardiolipin — a phospholipid essential for electron transport chain function and ATP synthesis.

Cardiolipin is selectively peroxidized in conditions of mitochondrial stress, leading to electron transport chain dysfunction, increased reactive oxygen species (ROS) production, and reduced cellular energy output. Elamipretide stabilizes cardiolipin, restoring electron transport chain efficiency and reducing oxidative damage (PMID 24991017).

Barth Syndrome

Barth syndrome is a rare X-linked genetic disorder caused by mutations in the tafazzin gene, which encodes an enzyme required for cardiolipin remodeling. Patients develop cardiomyopathy, skeletal muscle weakness, and growth retardation. Elamipretide has received FDA Breakthrough Therapy designation for Barth syndrome. Phase 3 TAZPOWER trial data showed statistically significant improvements in the 6-minute walk test — a functional measure of cardiorespiratory fitness and muscle endurance — in a patient population with very few treatment options (PMID 34310673).

Heart Failure with Reduced Ejection Fraction (HFrEF)

Mitochondrial dysfunction is increasingly recognized as a central feature of chronic heart failure. The EMPOWER-HF Phase 2 trial evaluated elamipretide in patients with HFrEF (ejection fraction ≤40%), demonstrating improvements in left ventricular end-systolic volume (LVESV) and ejection fraction — structural cardiac improvements that go beyond what most current heart failure medications can produce. Phase 3 programs are ongoing.

Orforglipron — The Oral GLP-1 Arrives

Orforglipron (LY3502970, Eli Lilly) is a non-peptide, small-molecule GLP-1 receptor agonist that can be taken orally without the food/water timing requirements that limit oral semaglutide (Rybelsus). Phase 3 ATTAIN and ACHIEVE programs have reported:

• Up to 9.4% body weight reduction vs. 2.0% placebo at 36 weeks in the ACHIEVE trial
• Meaningful HbA1c reduction in type 2 diabetes populations
• A pill form factor that removes the primary barrier to GLP-1 adoption: needle aversion

While orforglipron’s weight loss numbers are lower than injectable retatrutide or CagriSema, the oral delivery route represents a significant access breakthrough. An estimated 30–40% of patients who decline GLP-1 therapy do so because of injection reluctance. A once-daily oral pill that achieves even 8–10% weight loss at a competitive price point could reach populations that injectable GLP-1s never will (PMID 37395704).

AMG 133 — Bispecific Antibody Targeting GIP and GLP-1

AMG 133 (Amgen) takes a fundamentally different engineering approach to multi-receptor metabolic pharmacology. Rather than a peptide mimicking incretin hormones, AMG 133 is a bispecific antibody-peptide conjugate — a monoclonal antibody framework with GLP-1 receptor agonist peptides attached. One arm of the antibody antagonizes the GIP receptor (blocking it rather than activating it), while the attached peptides agonize the GLP-1 receptor.

This design is based on a pharmacological hypothesis that differs from tirzepatide: rather than activating GIP to potentiate GLP-1 effects, some researchers argue that GIP receptor antagonism may provide superior fat loss by preventing GIP-mediated lipid storage in adipose tissue. Phase 1/2 data showed up to 14.5% weight loss at 12 weeks with monthly dosing — an extremely steep early trajectory. Phase 2 is ongoing (PMID 38377453).

Pipeline Overview: Late-Stage Trials at a Glance

What the Pipeline Tells Us About the Field

Several patterns emerge when you look at the 2026–2027 trial landscape as a whole:

Multi-Receptor Strategies Are Winning

Every top-performing compound in the pipeline engages at least two receptor systems. Single-agonist GLP-1 drugs like semaglutide remain clinically dominant, but the next generation is built on the premise that metabolic diseases are multi-pathway problems requiring multi-target solutions. The research is consistently bearing this out: the highest weight loss percentages, the strongest liver disease outcomes, and the most compelling cardiovascular data are all coming from combination approaches.

MASLD/MASH Has Become a Primary Endpoint

Three of the six compounds described above have dedicated liver disease arms. This reflects the growing recognition that metabolic liver disease affects roughly 25% of the global adult population, has no approved pharmacological treatment beyond tirzepatide’s recent NASH indication, and is mechanistically linked to the same pathways (insulin resistance, hepatic fat accumulation, glucagon receptor signaling) that drive obesity and type 2 diabetes.

Oral Delivery Is Coming

Orforglipron’s Phase 3 success signals that oral GLP-1 receptor activation at meaningful efficacy levels is no longer a theoretical goal. As manufacturing scales and pricing normalizes, oral GLP-1 compounds may expand access to patient populations that injectable therapies never reached — including those in markets where weekly injection logistics are a significant barrier.

Antibody-Based Metabolic Therapy Is Early but Real

AMG 133’s bispecific antibody approach introduces a new engineering paradigm: instead of peptide mimicry of incretin hormones, use an antibody scaffold to selectively block or activate receptors with much longer half-lives (potentially monthly or quarterly dosing). If Phase 2 and 3 data hold, this could represent a third architectural generation of metabolic pharmacology after peptide agonists and small-molecule agonists.