De-escalating GLP-1 therapy from weekly to every-other-week dosing following weight normalization may be an effective strategy for maintaining both weight and metabolic improvements, new findings suggested.
“In my clinical experience, people who first reach a normal weight and improve their metabolic health following standard weekly dosing of GLP-1 drugs usually maintain it if they switch to every other week,” Mitch Biermann, MD, PhD, staff physician and investigator at Scripps Health, San Diego, told Medscape Medical News.
Biermann presented the findings on November 4, 2025, here at the Obesity Society’s Obesity Week 2025 meeting, where he noted that this study addresses a common patient concern about how long they’ll need to take the drug. GLP-1 drug cost and suboptimal insurance coverage lend urgency to the issue, he noted.
The idea for de-escalation by spreading out the frequency of drug dosing came from patients. “Patients were telling me they switched to taking it every other week…I started recommending it to people who wanted to de-escalate their therapy. There’s no current standard of care on how to de-escalate,” he noted, although Lilly’s SURMOUNT-MAINTAIN trial is examining de-escalation via dose reduction.
The study involved 30 patients with normalized weight and/or resolution of weight-related comorbidities who agreed to transition from weekly to every-other-week dosing of a GLP-1 medication. Of those, four regained weight and returned to weekly dosing. The other 26 continued on reduced frequency regimens, including 16 every 2 weeks, 5 every 10-14 days, and 5 greater than every 2 weeks. “They basically did what they wanted,” he commented.
Most were on nonmaximal doses throughout, with averages of 7.5 mg for tirzepatide and 1.7 mg for semaglutide, for a duration of 38 weeks prior to their weight plateau and/or metabolic normalization. They had lost an average of about 30 lb on weekly treatment, with a small but significant trend toward greater weight loss at 38 weeks after transitioning to every 2 weeks, of about 2-3 lb.
By percentage, they had lost an average of about 15%, followed by another 1% after moving to every-other-week dosing. Their average BMI at the start was 29.5, which dropped to 25 during weekly treatment and then to 24.5 after de-escalation.
Similar patterns were seen in body composition. The men lost an average of about 27% body fat and the women about 38%, decreasing to 21% and 32%, respectively, with weekly treatment, followed by a small, nonsignificant further loss in body fat after de-escalation.
Improvements achieved in A1c, triglycerides, and systolic blood pressure were also maintained or slightly improved following de-escalation, although not significantly.
“At least among patients who achieve normal weight and metabolic syndrome parameters taking these medications every week, they will likely remain successful even if you reduce the frequency. The dose doesn’t have to be the maximum, and the frequency doesn’t even have to be every other week,” he concluded.
Asked to comment, session moderator Kimberly A. Gudzune, MD, chief medical officer of the American Board of Obesity Medicine, told Medscape Medical News, “It’s a small study, and we definitely need more data to understand what’s the right approach for different patients long term, so this is an initial look at this approach.”
Pointing to the four who had regained weight with de-escalation, Gudzune cautioned, “If you’re going to try this, there really needs to be very close follow-up because you don’t want folks to lose all the health benefits that they gained.”
She also pointed out that this was a special study population. “They were all people who had quite dramatic results as far as their weight loss and their metabolic improvements…So that’s another caveat we need to be mindful of.”
Biermann reported having research relationships with Eli Lilly and Company and Novo Nordisk. Gudzune reported having no current disclosures.
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