GLP-1R agonists clinical trial design needs to be improved to reassure drugs’ benefits: GlobalData

Glucagon-like peptide-1 (GLP-1) receptor agonists, such as Wegovy and Mounjaro, have been dominating the news lately. The efficacy of these medicines in type 2 diabetes and obesity patients has been proven to be excellent in clinical trials and in the real world. However, some patients and physicians are still a bit skeptical about some of the effects and adverse events related to this drug class. Therefore, implementing some changes in the clinical trial design of GLP-1R agonists trials could lead to a better understanding of this drug class, according to key opinion leaders (KOLs) interviewed by GlobalData.

According to GlobalData, there are over 50 clinical trials for type 2 diabetes or obesity treatment involving GLP-1R agonists.

Costanza Alciati, Pharma Analyst at GlobalData, comments, “The main endpoints in GLP-1R agonist trials are HbA1c levels reduction, in the case of type 2 diabetes studies, and a reduction in body weight, measured with the body mass index (BMI), in the case of obesity studies. The problem with measuring the BMI to quantify the weight loss a patient is experiencing is that it gives no information about what share of fat mass is being lost vs. lean mass or muscle mass. For that reason, physicians may be more skeptical to prescribe a GLP-1R agonist as studies don’t fully characterize the nature of the weight lost.”

According to a high-prescribers survey conducted by GlobalData, a good implementation in obesity clinical trial design could be to use methods such as bioelectrical impedance analysis (BIA) and DEXA scanning to better assess fat loss and body composition in trial subjects.

KOLs have also highlighted the need for more data on physical function/ activity. With accelerated aging, which is a consequence of diabetes, someone’s physical condition worsens; therefore, it’s important to assess the physical activity levels of diabetes patients in clinical trials.

Alciati continues, “Another issue is patient representation. Representing the real-world population in clinical trials is one of the most important things in clinical studies. Race, gender, age, and status need to be considered when selecting patients. KOLs pointed out the fact that clinical study patients in GLP-1R agonists trials are usually in their 60s and 70s However, in practice, many patients are younger than that.”

There is an under-representation of women, women with child-bearing potential, and minority groups. This means that many patient populations are not well represented in the clinical trials, and that needs to be implemented.

Alciati concludes, “GLP-1R agonists can potentially help a huge number of patients. Hopefully, by implementing some changes in clinical trial design, patients and physicians will feel more reassured about the drugs’ benefits.”