GLP-1 Class Research Compounds Compared

Few areas of peptide research have moved as quickly as incretin pharmacology. Over roughly a decade, the field has progressed from single-receptor GLP-1 agonists to compounds designed to act on two and then three related hormone receptors.

This guide compares three of those compounds as research subjects: semaglutide, tirzepatide, and retatrutide. It covers what each is, which receptors it targets as described in the literature, how it has been studied, and its US regulatory status. It does not, and cannot, tell you which is “better” for any person. A&A Wellness products are for research use only and are not for human or veterinary use.

The Receptors Behind the “GLP-1 Class”

“GLP-1 class” is an informal label. The compounds in this family are defined by which of three related receptors they are designed to activate.

GLP-1 Receptor

Glucagon-like peptide-1 (GLP-1) is an incretin hormone released from the gut. Its receptor belongs to the class B G protein-coupled receptor (GPCR) family. GLP-1 receptor agonists are the oldest and most extensively studied group in this family.

GIP Receptor

Glucose-dependent insulinotropic polypeptide (GIP) is the second major incretin hormone. Its receptor is also a class B GPCR. Compounds that add GIP receptor activity to GLP-1 activity are often called dual agonists.

Glucagon Receptor

Glucagon is a pancreatic hormone whose receptor is closely related to the GLP-1 and GIP receptors. Adding glucagon receptor activity is the distinguishing design feature of retatrutide.

Side-by-Side Comparison

The table below summarizes each compound as a research subject. Receptor descriptions are as reported in the cited literature and FDA materials.

	Semaglutide	Tirzepatide	Retatrutide
Classification	Synthetic peptide analog of GLP-1	Synthetic peptide; dual incretin agonist	Synthetic peptide; triple hormone-receptor agonist
Receptor targets (as described in literature)	GLP-1 receptor	GIP and GLP-1 receptors	GIP, GLP-1, and glucagon receptors
Developer code / notes	Reference compound for the class	Once-weekly dual agonist	LY3437943
Research stage	Extensive phase 3 program; marketed	Extensive phase 3 program; marketed	Phase 3 (TRIUMPH program) as of 2026
US regulatory status	Active ingredient in FDA-approved prescription medicines	Active ingredient in FDA-approved prescription medicines (Mounjaro, Zepbound)	Investigational; not FDA-approved
Available from A&A as RUO material	No	Yes	Yes

Semaglutide is included as a reference point because it is the most widely published compound in the class and the benchmark against which newer compounds are usually discussed.

Semaglutide: The Single-Agonist Reference Point

What It Is

Semaglutide is a synthetic analog of human GLP-1, modified to extend its duration of action. It is the active ingredient in several FDA-approved prescription medicines.

How It Has Been Studied

The STEP clinical trial program is among the most cited bodies of work in the field. In STEP 1, published in the New England Journal of Medicine in 2021, 1,961 adults with overweight or obesity and without diabetes were randomized to once-weekly semaglutide or placebo for 68 weeks alongside lifestyle intervention. The authors reported a mean change in body weight of -14.9% with semaglutide versus -2.4% with placebo (Wilding et al., 2021).

For researchers, STEP 1 matters mainly as a design template: a large, placebo-controlled, 68-week trial with a percent-change-in-body-weight primary endpoint. Later compounds in the class have largely been studied against this template.

Tirzepatide: The Dual GIP/GLP-1 Agonist

What It Is

Tirzepatide is a synthetic peptide designed to activate both GIP and GLP-1 receptors. FDA describes it as the active ingredient in Mounjaro, approved for type 2 diabetes, and Zepbound, approved in November 2023 for chronic weight management in certain adults (FDA, 2023).

Research material is not the medicine. Research-grade tirzepatide sold for laboratory use is not Mounjaro or Zepbound, is not manufactured or distributed as a drug, and is not for human use.

How It Has Been Studied

SURMOUNT-1, published in the New England Journal of Medicine in 2022, randomized 2,539 adults with obesity or overweight (excluding diabetes) to one of three once-weekly tirzepatide dose groups or placebo for 72 weeks. The authors reported dose-dependent mean reductions in body weight across the tirzepatide groups compared with placebo, with gastrointestinal events the most commonly reported adverse events (Jastreboff et al., 2022).

The scientific interest for researchers lies in the GIP component. SURMOUNT-1 and related trials opened questions about how combined GIP and GLP-1 receptor activity compares with GLP-1 activity alone, questions that remain an active area of study.

Read the full compound profile: Tirzepatide.

Retatrutide: The Triple Agonist

What It Is

Retatrutide (LY3437943) is an investigational synthetic peptide described in the literature as an agonist of the GIP, GLP-1, and glucagon receptors. It is not approved by the FDA for any use.

How It Has Been Studied

A phase 2, double-blind, placebo-controlled trial published in the New England Journal of Medicine in 2023 randomized 338 adults with obesity or overweight to one of several once-weekly retatrutide dose groups or placebo for 48 weeks. The authors reported dose-dependent reductions in body weight, with the highest-dose group showing a mean change of -24.2% at 48 weeks versus -2.1% with placebo. Gastrointestinal adverse events were the most common and were described as dose-related and mostly mild to moderate. The authors also reported dose-dependent increases in heart rate that peaked at 24 weeks and declined thereafter (Jastreboff et al., 2023).

Retatrutide has since entered phase 3 under the TRIUMPH program. In May 2026, Eli Lilly announced topline results from TRIUMPH-1 by press release (Lilly, 2026). Company-announced topline results are not the same as a peer-reviewed publication, and researchers should treat them accordingly until full data are published.

Read the full compound profile: Retatrutide.

Reading the Trials as a Researcher

Cross-trial comparison has limits. STEP 1, SURMOUNT-1, and the retatrutide phase 2 trial enrolled different populations, ran for different durations (68, 72, and 48 weeks), and used different dose-escalation schemes. Setting their headline numbers side by side is tempting but methodologically weak. Head-to-head trials are the appropriate tool for direct comparison.

Phase matters. A phase 2 trial with a few hundred participants answers different questions from a phase 3 program with thousands. Retatrutide’s phase 2 data are an early signal; the phase 3 literature will define how it is understood.

Adverse event patterns recur. Across all three compounds, the cited trials report gastrointestinal events as the most common. Retatrutide’s heart-rate findings are one reason the glucagon component is studied closely.

Regulatory Status in Plain Terms

• Semaglutide and tirzepatide are active ingredients in FDA-approved prescription medicines. Research-use-only materials bearing those names are not those medicines.
• Retatrutide is investigational. FDA states that retatrutide “cannot be used in compounding under federal law” and is not a component of any FDA-approved drug (FDA).
• FDA has warned companies that sold products containing these compounds, labeled “for research purposes,” directly to consumers with dosing instructions. That is precisely the conduct a legitimate research supplier avoids.

For a broader look at the rules, see our US regulatory overview for research peptides.

Working With These Materials in the Lab

All three compounds are typically supplied as lyophilized powders. General handling conventions for this format are covered in our guides to lyophilized peptides and peptide storage.

Before starting any study, confirm identity and purity against batch documentation. Our guide to reading a COA explains what to look for. Learn more about our standards on the Quality page.

Browse the full research peptides category, or view retatrutide and tirzepatide research materials.