GLP-1 Pipeline Update: May 2025 - Prime Therapeutics
GLP-1 Pipeline Update: May 2025
Quarterly view of the GLP-1 pipeline and anticipated indications
Editorial team
Maryam Tabatabai, PharmD
Editor-In-Chief
Associate Vice President, Clinical Information
Carole Kerzic, RPh
Executive Editor
Drug Information Pharmacist Principal
Nicole Kjesbo, PharmD, BCPS
Executive Editor
Clinical Program Development Director Senior, Pipeline
DISCLAIMER
The drug pipeline is fluid; the dates and information within this publication are subject to change. Nothing herein is or shall be construed as a promise or representation regarding past or future events and Prime Therapeutics expressly disclaims any and all liability relating to the use of or reliance on the information contained in this presentation. The information contained in this publication is intended for educational purposes only and should not be considered clinical, financial, or legal advice. By receipt of this publication, each recipient agrees that the information contained herein will be kept confidential and that the information will not be photocopied, reproduced, distributed to, or disclosed to others at any time without the prior written consent of Prime Therapeutics.
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Introduction
The first glucagon-like peptide-1 receptor agonist (GLP-1) for type 2 diabetes mellitus (T2DM) was approved in 2005 and for chronic weight management in 2014. Researchers are still learning about their other potential uses. In 2024 semaglutide (Wegovy) became the first weight loss drug to also be approved for the reduction of risk of serious cardiovascular events in patients with cardiovascular (CV) disease and obesity and overweight. In late 2024 tirzepatide (Zepbound) became the first GLP-1 and first medication to be approved for sleep apnea. Plus semaglutide (Ozempic) now carries an indication for diabetic nephropathy. In 2025, Novo Nordisk’s semaglutide awaits several first-time FDA decisions:
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3Q 2025 – the first GLP-1 (Wegovy) for metabolic dysfunction-associated steatohepatitis (MASH)
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4Q 2025 – the first oral GLP-1 (oral formulation of Wegovy 25 mg) for weight loss and weight loss plus secondary CV risk reduction
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4Q 2025 – Wegovy for heart failure with preserved ejection fraction and obesity
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October 2025 – new indication for oral Rybelsus for secondary CV risk reduction
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2025 – Ozempic for T2DM and peripheral artery disease (PAD)
Given the considerable continued growth expected in the GLP-1 pipeline, Prime Therapeutic’s (Prime) talented team of clinical experts actively monitors this emerging landscape. The risk to benefit profile of these agents and outcomes data are key as we evaluate the evidence. Moreover, holistic care of patients remains a cornerstone of care.
Prime’s GLP-1 Pipeline Update provides a credible clinical snapshot of what is on the horizon. Keep reading to learn more, navigate to the FAQ below and visit the Quarterly Drug Pipeline for more clinical insights on anticipated drugs in development.
Access the complete GLP-1 Pipeline Update table for May 2025.
GLP-1s by year and indication
GLP-1s by indication and year
GLP-1 pipeline FAQs
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On Jan. 28, 2025, semaglutide (Ozempic) received FDA approval to reduce the risk of kidney disease worsening, kidney failure (end-stage kidney disease) and death due to cardiovascular disease (CVD) in adults with type 2 diabetes (T2DM) and chronic kidney disease (CKD). The Phase 3 FLOW trial evaluated Ozempic in patients with T2DM and CKD. The study reported that once-weekly doses of Ozempic 1 mg resulted in a significant reduction in the risk of kidney disease-related events compared to placebo.
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Novo Nordisk is awaiting new indications for their injectable semaglutide products.
- Wegovy for subcutaneous (SC) administration is undergoing a Priority Review from the FDA for the treatment of metabolic dysfunction-associated steatohepatitis (MASH), a fatty liver condition tied to obesity and T2DM. If approved, Wegovy will be the first GLP-1 agent to treat MASH. Topline results from the ESSENCE trial demonstrated that 62.7% of patients who received once-weekly Wegovy 2.4 mg SC had improved steatohepatitis and 37% had improved liver fibrosis compared 34.1% and 22.5%, respectively, of patients who received placebo. The FDA decision is anticipated in 3Q2025.
- Novo Nordisk resubmitted Wegovy for SC administration for the treatment of patients with heart failure with preserved ejection fraction (HFpEF) and obesity. A prespecified analysis of pooled data from the STEP-HFpEF and STEP-HFpEF DM trials demonstrated that significantly more patients treated with Wegovy 2.4 mg SC once weekly had an improvement of at least one NYHA functional class compared to those who received placebo (32.6% versus 21.5%, respectively; p<0.001) from baseline to 52 weeks. In addition, fewer Wegovy-treated patients experienced deterioration in New York Heart Association (NYHA) functional class compared to those who were given placebo (2.09% versus 5.24%, respectively; p=0.003). The FDA decision is anticipated in 4Q2025.
- Ozempic was submitted to the FDA for the treatment of patients with T2DM and peripheral artery disease (PAD). T2DM is a leading risk factor for PAD, which limits physical functions. Published data from the Phase 3b STRIDE trial reported that Ozempic 1 mg via SC injection once weekly improved maximum walking distance by 13% relative to placebo after 52 weeks. An FDA decision is expected in 2025.
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On May 1, 2025, Eli Lilly announced that it withdrew its FDA application for Zepbound (tirzepatide) for the treatment of HFpEF in patients with obesity, stating that the FDA requires an additional confirmatory trial to support the application.
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Novo Nordisk is awaiting new approvals for their oral semaglutide products.
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Novo Nordisk announced FDA acceptance of their New Drug Application (NDA) for a 25 mg oral version of Wegovy for two new indications: (1) chronic weight management in adults living with obesity or who are overweight with at least one comorbid condition, and (2) to reduce the risk of major adverse cardiac events (MACE) in adults with overweight or obesity and established CVD. If approved, Wegovy will become the first oral GLP-1 indicated for chronic weight management. The NDA was based on results from the OASIS-4 trial in adults with obesity or overweight. Patients with diabetes were excluded. Enrolled patients were randomized to once-daily oral Wegovy 25 mg or placebo, as an adjunct to lifestyle intervention for 64 weeks. Mean weight change was –13.6% in the Wegovy group versus –2.2% in the placebo group (p<0.0001). In addition, 79% of patients who received Wegovy compared to 31% who received placebo achieved at least 5% of their body weight (p<0.0001). The FDA decision is anticipated in 4Q 2025.
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A supplemental new drug application (sNDA) for Rybelsus to reduce the risk of MACE in people with T2DM and established CVD and/or CKD is awaiting an FDA decision. The SOUL cardiovascular outcomes trial (CVOT) demonstrated a 14% relative reduction in risk of MACE in patients treated with Rybelsus 14 mg orally once daily for approximately 5 years compared to those who received placebo. Moreover, risk reductions were seen across all components of MACE, namely cardiovascular death, non-fatal heart attack and non-fatal stroke. The FDA decision is anticipated in October 2025.
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The GLP-1s are being studied for a host of indications. There are several Phase 3 trials evaluating GLP-1s for conditions, such as prediabetes, Alzheimer's disease, diabetic retinopathy and osteoarthritis of the knee (in patients with obesity).
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Research in earlier phases or small trials include evaluation of GLP-1s for cystic fibrosis-related diabetes, polycystic ovarian syndrome (PCOS), chronic obstructive pulmonary disease (COPD), Prader-Willi syndrome (PWS), asthma, substance or alcohol use disorder and as add-on to insulin for type 1 diabetes. Many of these trials are very small; therefore, it is too early to predict if GLP-1s will provide benefit for patients with these conditions.
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GLP-1 receptors are expressed in several tissues in the body, including the gastrointestinal tract, heart, lung, kidney and brain. GLP-1s cause weight loss which has inherent health benefits, but the exact mechanism of GLP-1s for these other indications is not fully known. Evidence suggests that GLP-1 signaling may mediate inflammatory pathways involved in some metabolic, pulmonary and neurologic disorders. For example, in the lungs, GLP-1s may reduce the inflammatory response, improve oxidative stress, regulate protease/anti-protease imbalance, improve airway mucus homeostasis and reduce airway remodeling to provide benefit in patients with COPD. In the central nervous system (CNS), GLP-1s may impact neuronal function in conditions, such as Alzheimer's disease and Parkinson's disease, through multiple mechanisms. Data indicate that GLP-1s may reduce inflammation and tau phosphorylation and improve synaptic function. In addition, GLP-1s have the potential to impact substance or alcohol use disorder and Prader-Willi syndrome through their effect on satiety hormones.
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An area of interest for GLP-1 agents is their potential use in treating polycystic ovarian syndrome (PCOS). PCOS is a hormonal and metabolic disorder that occurs in women of reproductive age and is associated with high androgen levels and insulin resistance. Common manifestations include ovarian cysts, irregular menstrual periods, impaired fertility, obesity, hirsutism, acne and increased risk of cardiovascular disease. Currently, studies of GLP-1s for PCOS are inconclusive due to small sample population and heterogenicity between trials. However, available data has demonstrated that GLP-1-prompted weight loss is correlated with an improvement in menstrual regularity and pregnancy rate in participants with PCOS. GLP-1 therapy has also shown benefit in improving atherothrombosis markers (e.g., inflammation, endothelial dysfunction, clotting in this population).
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On Dec. 21, 2024, several generic versions of liraglutide (Victoza) for the treatment of T2DM became commercially available in the U.S. An authorized generic (AG) version launched in the U.S. in June 2024. Victoza is indicated for the treatment of T2DM.
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On Nov. 11, 2024, the FDA approved Amneal’s generic version of AstraZenaca’s exenatide injection (Byetta). This is the first generic for the GLP-1 receptor agonist. Byetta is indicated as an adjunct to diet and exercise in adults with T2DM and is dosed twice daily via SC injection. Amneal launched its generic in late November 2024. In addition, in October 2024, AstraZeneca announced that it will discontinue marketing brand Byetta.
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Generics for liraglutide (Saxenda) and dulaglutide (Trulicity) could be available in 2027.
Glossary
CKD Chronic kidney disease
CVD Cardiovascular disease
FDA Food and Drug Administration
GLP-1 Glucagon-like peptide-1
GLP-1s Glucagon-like peptide-1 receptor agonists
HF Heart failure
MASH Metabolic dysfunction-associated steatohepatitis
OA Osteoarthritis
OSA Obstructive sleep apnea
PAD Peripheral arterial disease
SC Subcutaneous
T2DM Type 2 diabetes mellitus
U.S. United States