Next-Level Obesity and Cardiovascular Care Starts with Clinical Trials.

This article was written by Jayme L. Leger, PhD, CDCES, CCRC, and Jean Young Park, MD.

MedStar Health researchers are exploring the next generation of anti-obesity medications—an oral GLP-1 RA medication and a triple-agonist drug—that could offer significant health benefits beyond weight loss. 

Almost everyone has heard about GLP-1 anti-obesity medications (AOMs) such as semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound). These injectables slow digestion, increase satiety, and have helped many people achieve a healthier weight.  

The benefits of AOMs go far beyond weight loss. Clinical trials have linked semaglutide, for example, with improvements in chronic kidney disease, blood pressure, certain types of heart failure, and even cognitive decline.

MedStar Health is exploring the next generation of AOM medications and offering our patients access to these therapies through clinical trials. 

Two new drugs are showing promise for cardiometabolic benefits beyond weight loss:

• Orforglipron: GLP-1 medication given as a daily pill instead of a weekly injection.

• Retatrutide: A triple-agonist injection that targets three hormones simultaneously.

While neither drug has yet been approved by the Food and Drug Administration (FDA), both are part of ongoing clinical research at MedStar Health. Let’s discuss what the latest research shows about their potential systemic health benefits and how patients can benefit from participating in clinical studies.

Orforglipron: GLP-1 receptor agonist in a daily pill.

From 2023 to 2025, MedStar Health served as a research site for the ATTAIN-1 trial, a phase III double-blind, placebo-controlled study of the safety and efficacy of the GLP-1 receptor agonist drug orforglipron. The trial included more than 3,100 adults with obesity or a weight-related medical problem, excluding diabetes,  and randomly assigned them to take a daily pill of either orforglipron or a placebo. 

The results, published in The New England Journal of Medicine in September 2025, showed that orforglipron is safe and effective for weight loss—and offers additional cardiovascular benefits.

Study participants at all three orforglipron dose levels (6 mg, 12 mg, and 36 mg) showed improvements in blood pressure, triglycerides, and cholesterol. After 72 weeks of treatment, more than half of the patients in the medication group lost at least 10% of their body weight and had a smaller waist circumference. More than 18% of participants lost 20% or more of their total body weight. Participants who took the highest dose lost the most weight. Among patients with prediabetes at the start of the study, 91% achieved healthy blood sugar levels in the medication group, compared with 42% in the placebo group. Safety and side effects were similar to those of previously approved GLP-1 receptor agonists. 

If approved by the FDA, orforglipron will be the first oral GLP-1 medication for weight loss. Taking a pill instead of a shot may appeal to patients for many reasons, including:

• Injections require refrigeration; pills do not

• Pills are less expensive to manufacture than self-injection pens, which could drive down the cost

• Adding a pill to other daily medications may be an easier habit to form than remembering a weekly injection
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Retatrutide: A triple-agonist injectable.

Triple-agonists are a newer type of medication that binds to and activates three distinct receptor types simultaneously—the goal is to achieve a stronger effect. Retatrutide, a once-weekly injection, makes the body more efficient at regulating appetite, digestion, and energy expenditure by activating these three receptors:

• Glucose-dependent insulinotropic polypeptide (GIP)

• Glucagon-like peptide 1 (GLP-1)

• Glucagon (GCG)

Phase-2 clinical trial data published in the New England Journal of Medicine showed that the drug is effective for weight loss. All patients lost at least 5% of their bodyweight; the 8mg dose lost at least 5% of their bodyweight, and more than 90% of participants at the highest dose (12mg) lost 10% or more. 

Patients also showed notable cardiometabolic improvements, including lower blood pressure, lower fasting blood sugar, and lower insulin levels. And 72% of participants with prediabetes at the start of the study had normal blood sugar levels while taking the medication.

Now, MedStar Health is undertaking two phase III randomized clinical trials to understand the potential benefits of retatrutide beyond weight loss:

• TRANSCEND-T2D-2 includes adult participants who take metformin alone or with an SGLT2 inhibitor for Type 2 diabetes. Patients were randomly assigned to take either retatrutide or semaglutide to compare their safety and effectiveness specifically for blood sugar control. Read about the TRANSCEND-T2D-2 trial.

• TRIUMPH-Outcomes enrolled adults with chronic kidney disease or atherosclerotic cardiovascular disease with obesity, a body mass index (BMI) of 27 or higher. Patients were randomly assigned to groups that received retatrutide or a placebo. The goal is to learn whether taking retatrutide can prevent worsening kidney function or reduce the risk of heart-related complications. Explore the TRIUMPH-Outcomes trial.
  
  

Clinical trials open doors to long-term health.

People have different motivations for joining clinical trials: Altruism, access, and action. Another great reason to join is to get even more comprehensive care. 

In a clinical trial, patients receive closer attention to a specific health condition than is usually possible in a typical clinic setting. Along with standard care, trial participants can also try advanced medications before they are widely available to the public. In some cases, these benefits align and lead to a healthier future for the patient—and sometimes a new approach to treating complex conditions such as obesity.

In this way, MedStar Health’s research and clinical care approaches come together. We bring a deep bench of experts who can dive deep into specific aspects of a patient’s health to curate the care they need. And we can see the big picture of how the treatment decisions we make today can ripple across a patient’s future health.

Because obesity is multifactorial, there likely will never be a singular pill, injection, or care plan that fits every patient. That is why MedStar Health continues to invest in obesity care and cardiometabolic research. With every discovery through clinical studies, we can offer more people the chance for a healthier future.