GLP-1 Less Frequent Dosing May Maintain Weight Loss

TOPLINE:

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) administered at off-label reduced dosing maintained weight-loss benefits, with patients retaining the effects even with 2-4 weeks between doses.

METHODOLOGY:

• GLP-1 RAs are transforming obesity treatment, but high costs and shortages limit patient access. Clinicians have suggested a less frequent dosing to maintain weight loss, but evidence supporting its effectiveness is lacking.
• Researchers used a combination of real-world case reports and mathematical modeling to examine the efficacy of a less frequent dosing of GLP-1 RAs for weight maintenance.
• They analyzed the data of two patients who used GLP-1 RAs at less frequent dosing schedules than recommended; patient 1 with obesity and prediabetes self-administered 7.5 mg tirzepatide every 10-14 days, whereas patient 2 with uncontrolled type 2 diabetes managed intermittent dosing of 15 mg tirzepatide due to supply shortages.
• A mathematical pharmacokinetic-pharmacodynamic model was used to simulate long-term changes in body weight of virtual patients administered semaglutide and tirzepatide at various dosing intervals.
• Simulations modeled semaglutide (2.4 mg) or tirzepatide (5 mg, 10 mg, or 15 mg) as a once-weekly dosing for 120 weeks, after which the 7-day dosing interval was increased to 10, 14, or 28 days or retained.

TAKEAWAY:

• Patient 1 achieved an additional 13.7% body weight loss over 7 months and maintained it thereafter. Patient 2 lost 30% of her body weight and safely stopped insulin; even with intermittent dosing of tirzepatide, she retained a 22.8% body weight loss from baseline.
• Mathematical modeling predicted that switching from one dose per week to one dose every 2 weeks maintained 72% and 78% of the body weight loss achieved with 2.4 mg semaglutide and 15 mg tirzepatide, respectively.
• Even monthly dosing may have preserved half of the body weight loss achieved with weekly dosing, demonstrating that the reduction in efficacy was not proportional to the reduction in dosing frequency.

IN PRACTICE:

“Future studies are needed to identify patient factors that predict a more favorable response to less frequent dosing of incretin mimetics and to examine the long-term clinical outcomes achieved through this approach compared with other off-ramping options (eg, switching to alternative AOMs [anti-obesity medications]),” the authors wrote.

SOURCE:

This study was led by Calvin C. Wu, Tono Health, Brooklyn, New York. It was published online in Obesity.

LIMITATIONS:

No limitations were provided for this study.

DISCLOSURES:

Two authors reported receiving funding from the National Science Foundation.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.