insights

Current Clinical Research Trends in GLP-1 (Glucagon-Like Peptide 1) Treatment

The recent surge in GLP-1 treatments has ignited a profound shift in the pharmaceutical landscape, with more studies being announced than ever before. Due to this meaningful change, the first-ever GLP-1-Based Therapeutics Summit took place in Philadelphia on May 15-16th, 2024, serving as a platform for industry decision-makers to provide invaluable insights for therapeutic strategies. As they are at the forefront of the evolving role of GLP-1s (Glucagon-Like Peptide 1) in treating metabolic disorders, our metabolic experts, MarieElena Cordisco, Scott Beasley, and Alexis Bailey, attended this conference. Check out their key takeaways:

The Role of GLP-1 in Obesity Treatment

GLP-1s have emerged from treatment in Type 2 Diabetes to a frontline treatment for obesity due to their efficacy in promoting significant weight loss. However, the treatment journey does not end with weight reduction, as maintaining weight loss overall is equally crucial. The discussions at the conference shed light on innovative approaches to enhance long-term outcomes for patients, focusing on combination therapies that not only aid in weight loss but also help preserve muscle mass, an essential component of healthy body composition.

Since tolerability remains a hurdle in the widespread adoption of GLP-1 treatments, experts at the summit discussed the potential of these combination therapies to mitigate treatment side effects and improve patient adherence. These strategies are critical for enhancing the overall success of GLP-1 therapies in clinical practice.

GLP-1 Drug Class: Market Overview

The market for GLP-1 medications is expanding, with several establishing options and numerous promising therapies on the horizon. The GLP-1 medications currently approved and used in clinical practice, primarily for the treatment of type 2 diabetes and obesity, include:

  • Semaglutide: Ozempic, Wegovy, Rybelsus
  • Tirzepatide: Mounjaro, Zepbound
  • Liraglutide: Victoza, Saxenda
  • Dulaglutide: Trulicity
  • Exenatide: Byetta, Bydureon

Expanding Beyond Obesity

The therapeutic potential of GLP-1s extends beyond weight management. Recent trials and off-label use suggest benefits in areas such as:

  • Chronic kidney disease
  • Neurological disorders: Alzheimer’s disease, dementia, & Parkinson’s disease
  • Cardiovascular diseases: Heart failure & stroke
  • Women’s health: Polycystic ovary syndrome
  • Gastrointestinal disorders: Gastroparesis & functional dyspepsia
  • Sleep apnea
  • Alcohol use disorder

These findings open new avenues for the application of GLP-1 therapies and underscore the need for ongoing research.

Challenges in GLP-1 Medication Usage

Despite the emerging therapeutic benefits of GLP-1 medications, these treatments also face several challenges, including:

Patient Compliance Due to Side Effects

One considerable challenge of GLP-1 treatments is their administration method, which is typically a daily injection. While effective in managing weight and glucose levels, the requirement of a daily injection often leads to poor adherence among patients. Many individuals find the injection regimen cumbersome, contributing to a high discontinuation rate, with some data showing that only about 20% continuing treatment beyond a year. PA potential solution for this challenge is to explore formulations offering less frequent injections andral formulations, which may provide a more viable long-term treatment solution.

Additionally, the initial weight loss typically slows, which can frustrate participants who may expect faster results. This dissatisfaction with results, paired with the requirement for self-injections and GI side effects, often leads to interruptions in the treatment cycle. As a result, many patients experience a rebound effect, quickly gaining weight back and then resuming GLP-1 treatments. This cycle may be repeated numerous times and results in significant muscle wasting in patients, thereby increasing the risk of falls and fractures, particularly in the elderly population. Studies have shown that in such rebound cases, much of the weight loss is in lean muscle mass, which is less likely to be restored without some form of weight-bearing exercise.

Global Shortage

The global shortage of GLP-1 treatments has also emerged as another critical issue, significantly affecting accessibility, particularly in underserved populations and lower-income regions. The demand for these medications, which play a vital role in managing diabetes and obesity, has far outpaced production capabilities, leading to widespread scarcity. This shortage is most prevalent in the starting doses and is leading to extensive issues with patient access and delays in clinical trial start-up times as most of the obesity trials incorporate initiating GLP-1 agonist as part of the protocols.

Ethical Considerations

During clinical trials, participants are either already on a stable, maintenance dose or are provided with the GLP-1 medication for the study’s duration. However, once the trial concludes, the drug is no longer given to the patients, leading to concerns about the continuity of care and managing expectations post-study, particularly in regard to the detrimental effects of weight gain and muscle wasting once the participant stops taking the medication. It is important to ensure that patients provide truly informed consent and understand the terms of participation and that they require their own physician’s prescription post-study if they are to continue receiving GLP-1 therapeutics.

Worldwide’s Solutions to Addressing GLP-1 Treatment Challenges

At Worldwide, we are actively leading initiatives to address the multifaceted challenges associated with GLP-1 treatments. One solution we are exploring to help address the global shortage is the utilization of biosimilars in clinical trials, as we are looking into what this would look like with GLP-1s and what potential challenges and solutions may be. We are also collaborating closely with vendors to strategically stock up on low-dosage GLP-1 medications to minimize study delays as much as possible without impacting supply for standard of care for T2DM patients.

In addressing metabolic dysfunction, Worldwide leverages expertise from Key Opinion Leaders who highlighted the critical link between obesity-related metabolic disorders and conditions like Metabolic dysfunction-associated steatohepatitis (MASH). Our metabolic team is actively involved in advancing clinical trials that explore GLP-1’s potential to reduce liver fat, mitigate inflammation, and ultimately improve outcomes for patients at risk of liver disease progression.

Further research is needed but it is known that combination therapies with GLP-1s and other compounds, such as Glucagon which has potent effects on fat and increased energy expenditure, may be utilized to reset the metabolism to a point where GLP-1s may not need to be taken as frequently. Glucagon also spares the GLP-1 effects potentially reducing side effects leading to increased compliance.

Such advances, along with patient education, lifestyle coaching, and modification, are likely to enhance the patient experience, resulting in sustained treatment and weight maintenance and reduced muscle wasting synonymous with using GLP-1s.

As GLP-1s continue to expand into other diseases, Worldwide continues to work cross-functionally across indications, providing personalized solutions to each study. With our tailored approach, we can bring on the right people with experience in GLP-1s regardless of indication.

The Future of GLP-1 Treatments

We understand that obesity and other metabolic conditions are systematic issues stemming from flaws in our healthcare systems, the food industry, and lifestyle choices. Looking forward, we are committed to a comprehensive approach that can address the root causes of metabolic and cardiovascular diseases. By focusing on innovation, patient-centric solutions, and cross-functional collaboration, we aim to continue leading the charge in transforming the GLP-1 therapeutic landscape.

Want to learn more about Worldwide Clinical Trials?