GLP-1 Drug Class: Approved & Pipeline Registry

What Is the GLP-1 Drug Class?

Glucagon-like peptide-1 is an incretin hormone secreted by intestinal L-cells in response to food intake. It stimulates insulin secretion in a glucose-dependent manner, suppresses glucagon release, slows gastric emptying, and signals satiety through central nervous system pathways. GLP-1 receptor agonists (GLP-1 RAs) are synthetic compounds designed to mimic or extend these effects by binding to the GLP-1 receptor.

The first GLP-1 RA approved by the FDA was exenatide (Byetta), cleared in 2005 for type 2 diabetes management. Since then, the class has expanded to include daily and weekly injectable formulations, an oral tablet, and dual-agonist compounds that also target the glucose-dependent insulinotropic polypeptide (GIP) receptor. The class is now among the most actively researched in metabolic medicine.

All FDA approvals in this class are for specific branded pharmaceutical products manufactured under regulated conditions. Research-chemical or compounded versions of the same peptide sequences are not covered by those approvals and carry a different regulatory and safety profile. This registry distinguishes the two categories throughout.

FDA-Approved GLP-1 Receptor Agonists

Exenatide (Byetta, twice-daily injection) received FDA approval in April 2005 for type 2 diabetes. A once-weekly extended-release formulation, Bydureon BCise, was approved in January 2012. Liraglutide (Victoza) was approved in January 2010 for type 2 diabetes, and a higher-dose formulation marketed as Saxenda received a separate approval in December 2014 for chronic weight management in adults with obesity or overweight with at least one weight-related condition.

Dulaglutide (Trulicity), a once-weekly injectable, was approved in September 2014 for type 2 diabetes and later received a cardiovascular risk-reduction indication in 2020 based on the REWIND trial, which enrolled 9,901 participants and was published in The Lancet in 2019. Semaglutide (Ozempic, once-weekly injectable) was approved in December 2017 for type 2 diabetes. Rybelsus, an oral semaglutide tablet, was approved in September 2019, marking the first oral GLP-1 RA cleared by the FDA. Wegovy, a higher-dose semaglutide injection, was approved in June 2021 for chronic weight management.

Tirzepatide is a dual GIP/GLP-1 receptor agonist approved as Mounjaro in May 2022 for type 2 diabetes and as Zepbound in November 2023 for chronic weight management. Semaglutide (Wegovy) received an additional cardiovascular indication in March 2024 based on the SELECT trial, a 17,604-participant cardiovascular outcomes study published in the New England Journal of Medicine in 2023. Albiglutide (Tanzeum) and lixisenatide (Adlyxin) were both approved but have since been withdrawn from the U.S. market for commercial reasons, not safety findings.

• Exenatide (Byetta): approved April 2005, type 2 diabetes
• Exenatide ER (Bydureon BCise): approved January 2012, type 2 diabetes
• Liraglutide (Victoza): approved January 2010, type 2 diabetes
• Liraglutide (Saxenda): approved December 2014, chronic weight management
• Dulaglutide (Trulicity): approved September 2014, type 2 diabetes and CV risk reduction
• Semaglutide (Ozempic): approved December 2017, type 2 diabetes
• Oral semaglutide (Rybelsus): approved September 2019, type 2 diabetes
• Semaglutide (Wegovy): approved June 2021, chronic weight management; CV indication added March 2024
• Tirzepatide (Mounjaro): approved May 2022, type 2 diabetes
• Tirzepatide (Zepbound): approved November 2023, chronic weight management

Pipeline GLP-1 and Dual-Agonist Candidates

Orforglipron is an oral, non-peptide GLP-1 receptor agonist developed by Eli Lilly. Phase 3 trials are ongoing as of 2024, with registration identifiers including NCT05048719. Phase 2 data published in the New England Journal of Medicine in 2023 showed dose-dependent weight reductions in a 272-participant trial over 36 weeks. Because it is a small molecule rather than a peptide, it does not require refrigeration, which distinguishes it from current injectable and oral peptide options.

Retatrutide is a triple agonist targeting GLP-1, GIP, and glucagon receptors, also in development at Eli Lilly. Phase 2 results published in the New England Journal of Medicine in 2023 reported up to 24.2 percent mean weight reduction at 48 weeks in a 338-participant obesity trial. Phase 3 trials are underway. Cagrilintide combined with semaglutide (CagriSema, Novo Nordisk) is a co-formulation pairing a GLP-1 RA with an amylin analogue; Phase 3 data are expected in 2025.

Mazdutide (IBI362), developed by Innovent Biologics, is a GLP-1/glucagon dual agonist in Phase 3 trials in China with Phase 2 data published in The Lancet Diabetes and Endocrinology in 2023. Pemvidutide (ALT-801), a GLP-1/glucagon dual agonist from Altimmune, reported Phase 2 results in 2024. None of these pipeline compounds have received FDA approval as of this registry's last update. All evidence cited for pipeline agents comes from Phase 2 or early Phase 3 human trials, not completed pivotal studies.

How Do Approved GLP-1 Drugs Differ From Research Peptides?

FDA-approved GLP-1 drugs are manufactured under current Good Manufacturing Practice (cGMP) regulations, subjected to rigorous purity and sterility testing, and dispensed through licensed pharmacies under a valid prescription. Their safety and efficacy data come from large-scale randomized controlled trials with thousands of participants and years of follow-up.

Research-grade peptides sold by chemical suppliers may share the same amino acid sequence as an approved drug's active ingredient, but they are not manufactured under the same regulatory framework, have not completed the same approval pathway, and are not authorized for human therapeutic use. The FDA has issued guidance distinguishing compounded semaglutide from the approved branded products, particularly during periods of drug shortage. Readers seeking treatment with any GLP-1 medication should consult a licensed healthcare provider who can prescribe and monitor an approved pharmaceutical product.

This registry does not list research peptide vendors or endorse any specific supplier. Its purpose is to document the regulatory record of the GLP-1 drug class so that readers can orient themselves within the approved and investigational landscape before speaking with a qualified clinician.

Evidence Tiers Across the GLP-1 Class

The approved agents in this class are supported by some of the largest cardiovascular outcomes trials in metabolic medicine. The LEADER trial for liraglutide (9,340 participants, published in NEJM 2016), SUSTAIN-6 for semaglutide (3,297 participants, NEJM 2016), REWIND for dulaglutide (9,901 participants, The Lancet 2019), and SELECT for semaglutide (17,604 participants, NEJM 2023) each met their primary endpoints for cardiovascular event reduction in high-risk populations. These are Phase 3 randomized controlled trials, the highest evidence tier in clinical research.

Pipeline agents are currently supported by Phase 2 RCT data, which establishes dose-response relationships and short-term safety signals but does not yet confirm long-term cardiovascular or mortality outcomes. Readers should weigh evidence tiers carefully: a Phase 2 result in 300 participants over 48 weeks is meaningful but not equivalent to a 17,000-person outcomes trial spanning several years.

Animal and in-vitro studies have explored GLP-1 receptor activity in contexts beyond metabolic disease, including neurodegeneration and inflammation. These findings are preclinical and have not been replicated in large human trials. Any claim that a GLP-1 compound produces neuroprotective or anti-inflammatory effects in humans should be evaluated against the specific evidence tier supporting it.