With the new generation of anti-obesity medications such as Wegovy and Zepbound, adherence is key, as patients must remember to take them weekly. However, a new medication taken less frequently may offer similar results.
In a Phase II clinical trial, researchers found maridebart cafraglutide (MariTide) was effective at reducing weight in patients with obesity with just once-monthly doses. And this was true for patients with or without type 2 diabetes.
The trial results were recently reported in the New England Journal of Medicine.
Ania Jastreboff, MD, PhD, professor of medicine (endocrinology) at Yale School of Medicine and director of the Yale Obesity Research Center (Y-Weight), served as the principal investigator for the Phase II trial evaluating the safety and efficacy of MariTide.
Beyond GLP-1
MariTide works by targeting the action of two hormones: glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Both hormones are involved in the regulation of blood sugar and, importantly, they target the brain mechanisms associated with obesity.
Like several approved treatments, MariTide works at the receptor for GLP-1, activating it by mimicking the natural hormone. Uniquely, MariTide also blocks the action of GIP at its receptor. This dual action is thought to both help the body regulate blood sugar and treat obesity.
The trial included two groups of patients: 465 people with obesity (defined as a body mass index of over 30 or over 27 with an obesity-related disease) and 127 with both obesity and type 2 diabetes. During the year-long trial, study participants received MariTide in various dosages at a frequency of once per month or once every other month.
Overall, the study showed that the obesity-only cohort lost up to an average of 20% of their body weight, while the obesity-diabetes cohort lost up to an average of 17% of their body weight. Hemoglobin A1c, a measure of blood glucose levels, decreased up to an average of 2.2% in the patients with diabetes.
The fact that both cohorts of patients—those with and without type 2 diabetes—lost weight at similar rates was a surprise to Jastreboff and her colleagues.
“This was an intriguing finding,” says Jastreboff. “Usually with the medications in this class, we observe less weight reduction in patients with obesity and type 2 diabetes than in those who have obesity alone. In this study, the discrepancy between participants with and without diabetes was not as large as we usually observe.”
Patients enrolled in the study reported mostly mild to moderate side effects including nausea, vomiting, constipation, and diarrhea consistent with other medications in this class. A more gradual increase in dosage, tested in several groups in the obesity-only cohort, was associated with fewer gastrointestinal side effects.
Clinical trials are conducted in four phases. A Phase I trial assesses how the body interacts with the drug and evaluates safety in a small number of participants, while a Phase II trial assesses safety, tolerability, and efficacy in a few hundred participants. A Phase III trial expands the number of participants to a large group to assess whether the new treatment leads to better outcomes, monitoring side effects while evaluating efficacy, and a Phase IV trial, conducted after a medication has been approved by the U.S. Food and Drug Administration, assesses long-term outcomes, risks, and benefits.
Treating obesity and type 2 diabetes
The promise of these drugs is immense, as obesity is both a chronic disease and a leading cause of death and disability in the United States. Currently, about 42% of adult Americans are classified as having obesity, according to the U.S. Centers for Disease Control and Prevention. Of the 38 million Americans with diabetes, up to 95% of them have type 2 diabetes and almost 90% are also classified as overweight or having obesity.
Left untreated, diabetes leads to high levels of blood sugar, which can cause heart disease, nerve damage, and kidney disease, among other risks. These health risks underscore the promise of the emerging generation of medications that can have a significant impact on improving health.
Jastreboff says that while more research is needed to understand the underlying mechanisms by which MariTide might be helping patients with and without diabetes lose weight at similar rates, the Phase II trial results are promising. The ability for patients to require less-frequent dosing of the medications could lead to improved adherence to treatments and better overall health outcomes.
Currently, Jastreboff and her colleagues are conducting the Phase III study assessing once-monthly MariTide dosages in the MARITIME-1 trial at Y-Weight.
If you are interested in taking part in this or other clinical trials investigating novel anti-obesity medications, please email Yweight@yale.edu.
The research reported in this news article was supported by Amgen and Yale University.