Adults with type 2 diabetes experienced considerable weight loss with a new investigational combination treatment involving eloralintide and tirzepatide (Mounjaro, Zepbound), according to findings from a phase IIb clinical trial.
Trial Outcomes
In this 10-arm study, participants receiving the highest dose of eloralintide combined with tirzepatide lost an average of 23.3% of their body weight over 48 weeks, which was a notable increase compared to the 14.8% weight loss observed in those treated with tirzepatide alone.
Dr. Liana Billings from Endeavor Health indicated during her presentation at the European Association for the Study of Diabetes (EASD) annual meeting in Milan that these trends suggest potential for ongoing weight reduction.
Comparison with Existing Treatments
For context, tirzepatide at a dose of 15 mg is a well-established GLP-1 therapy for managing type 2 diabetes and weight. The weight loss seen in this study is unprecedented compared to previous findings in diabetic populations.
The weight loss achieved in this study exceeded that observed with tirzepatide in non-diabetic individuals, which was reported at 20.9%. Typically, patients with type 2 diabetes experience less weight loss on GLP-1-based treatments than their non-diabetic counterparts.
High Rates of Significant Weight Loss
Notably, a quarter of participants receiving the highest dose of the combined treatment lost at least 30% of their body weight. This level of weight loss aligns with benchmarks typically associated with metabolic surgery, in contrast to 12% of the participants treated with tirzepatide alone.
Mechanism of Action
Eloralintide functions as a selective amylin receptor agonist, while tirzepatide is a dual GIP/GLP-1 receptor agonist. The design behind this combination therapy aims to activate three complementary hormones stimulated by nutrients—GIP, GLP-1, and amylin—while minimizing activity at the calcitonin receptor.
Each of these hormones is naturally released by the body after eating, playing a unique role in regulating hunger and blood glucose levels.
Personalized Treatment Opportunities
Dr. Billings emphasized that this combination therapy provides clinicians with a unique opportunity to tailor treatment for patients, addressing both weight management and glucose control through varied doses and combinations.
She also pointed out the interconnectedness of obesity and type 2 diabetes, highlighting the potential benefits of targeting multiple hormonal pathways.
Blood Sugar Control Achievements
Remarkably, 96% of participants in the highest-dose combination group achieved an HbA1c level below 7%, a significant clinical benchmark similarly achieved by those receiving tirzepatide alone.
This is considered the standard goal for blood glucose management, and Dr. Billings described the fact that all patients could reach this goal as “quite remarkable.” Additionally, 77% of participants in the combination group attained an HbA1c level below 5.7%, compared to 66% in the tirzepatide-only group.
Side Effects and Treatment Discontinuation
Despite the impressive weight loss and glycemic control observed, the tolerability of the combination treatment was found to be less favorable. About 84% of participants in the highest-dose eloralintide-tirzepatide group experienced treatment-emergent adverse events, compared to 71.4% in the tirzepatide-alone group. Furthermore, nearly 10 times more participants in the combination group discontinued treatment due to adverse effects (27% vs. 2.9%).
Study Design and Future Directions
This randomized, double-blind, parallel-group trial included 367 adults with obesity or overweight and type 2 diabetes across the U.S. and Argentina, divided into 10 equal groups: one placebo group, three groups receiving eloralintide monotherapy, one group on tirzepatide monotherapy, four groups on the combination therapy, and one group that began treatment with tirzepatide and added eloralintide at 24 weeks.
The combination therapy was administered via two separate injections; however, plans are underway to develop a single-injection formulation.
Although one death occurred among participants in the lowest-dose combination group, investigators concluded it was unrelated to the study drug.
Eloralintide is currently being evaluated in phase III trials as a standalone treatment for obesity. Eli Lilly aims to progress the eloralintide-tirzepatide combination into phase III development before the year ends.
Disclaimer: This information is provided for educational purposes only and should not be considered medical advice. Always consult a healthcare professional for medical advice and treatment options.
Fuente: https://www.medpagetoday.com/meetingcoverage/easd/123239
Join the doctors who get the most relevant medical news, curated by specialty, every week — no spam, unsubscribe anytime.
