GLP-1 Pipeline Update: February 2025 - Prime Therapeutics
GLP-1 Pipeline Update: February 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.
All brand names are property of their respective owners.
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 disease and obesity or overweight. In late 2024, tirzepatide (Zepbound) became the first GLP-1 and first medication to be approved for sleep apnea. And semaglutide (Ozempic) now carries an indication for diabetic nephropathy. Given the considerable continued growth expected in the GLP-1 pipeline, Prime Therapeutics’ (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 February 2025.
GLP-1s by year and indication
GLP-1s by indication and year
GLP-1 pipeline FAQs
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Obstructive sleep apnea (OSA): On Dec. 20, 2024, the FDA approved tirzepatide (Zepbound) for the treatment of moderate-to-severe OSA in adults with obesity, with and without positive airway pressure (PAP) therapy, making it the first GLP-1 indicated for OSA. The approval was supported by results from the SURMOUNT-OSA trial that revealed Zepbound led to a significant reduction in the apnea-hypopnea index at 52 weeks compared to placebo in individuals who were and were not receiving PAP therapy.
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Diabetic nephropathy: 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 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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While positive airway pressure (PAP) is effective in keeping the upper airway open during sleep in individuals with moderate to severe OSA, about 30% to 50% of patients will discontinue PAP within the first year due to the cumbersome and uncomfortable nature of the device. Weight loss can also improve OSA in patients with obesity or overweight as seen with the FDA approval of tirzepatide (Zepbound) and in clinical trials of the investigational GLP-1 agent orforglipron. Neither PAP nor GLP-1s treat the underlying cause of OSA. Investigational treatments that address the underlying airway obstruction of OSA include AD109 and IHL-42X.
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Apnimed is currently studying AD109 for use in adults with OSA. AD109 is an oral combination of the selective norepinephrine reuptake inhibitor, atomoxetine, and the selective antimuscarinic, aroxybutynin. Both drug classes have demonstrated ability to increase genioglossus muscle activity, thus preventing upper airway collapse during sleep. The Phase 2b MARIPOSA trial evaluated oral bedtime doses of AD109 in adults with mild to severe OSA and included patients with or without obesity and those with or without prior use of PAP therapy. In the study, AD109 led to dose-dependent decreases in the placebo-adjusted change from baseline in the primary endpoint of apnea–hypopnea index (AHI). Two Phase 3 trials for AD109 with similar design to MARIPOSA are ongoing with topline results anticipated in mid-2025. Apnimed anticipates submitting AD109 for FDA review in 2H2025.
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IHL-42X is an oral fixed-dose combination of the carbonic anhydrase inhibitor, acetazolamide, and the cannabinoid, dronabinol, by Incannex. The product is designed to synergistically target two different physiological pathways of intermittent hypoxia (IH) and hypercapnia seen with OSA. IHL-42X is being evaluated in the Phase 2/3 REPOSA trial in adults with OSA who are PAP-experienced or -naïve and regardless of body weight (excluded patients with BMI > 45 kg/m²). The study is anticipated to complete in December 2026.
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The GLP-1s are being studied for a host of conditions. There are several Phase 3 trials evaluating GLP-1s for conditions, such as metabolic dysfunction-associated steatohepatitis (MASH), 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 (T1DM). 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 CNS, GLP-1s may impact neuronal function in conditions, such as Alzheimer's disease and Parkinson's disease, through multiple mechanisms. Data indicates 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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Another 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 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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Typically, gastrointestinal (GI) side effects of GLP-1s, such as nausea and vomiting, are dose-dependent, mild-to-moderate in severity and occur mostly during initiation of therapy and up-titration. GI side effects of GLP-1s can be mitigated with appropriate dose escalation when initiating therapy. Patients prescribed a GLP-1 agent should also be encouraged to eat slowly, eat smaller meals and if needed, adjust the timing of their GLP-1 dose in relation to food intake.
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There are no medications available in the U.S. indicated specifically to treat GI side effects from GLP-1s. Neurogastrx is studying the peripherally acting dopamine D2/D3 receptor antagonist investigational drug, metopimazine, for reducing the incidence, duration and severity of nausea and vomiting in individuals who received a single SC dose of semaglutide. Top-line results of the Phase 2 trial demonstrated metopimazine led to a 40% reduction in the incidence of nausea and a 56% reduction in frequency of vomiting.
- 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.
- 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 subcutaneous injection. Amneal launched its generic in late November 2024. In addition, in October 2024, AstraZeneca announced that it will discontinue marketing brand Byetta.
- Generics for liraglutide (Saxenda) and dulaglutide (Trulicity) could be available in 2027. Generics for other GLP-1 agents are expected sometime after 2027.
Glossary
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