Patients with plateaued weight loss or who reached their weight-related goals on a GLP-1 receptor agonist were able to maintain their improvements in weight, body composition, and metabolic improvements after they reduced the frequency of their dose, according to a recent case series.

Among 30 patients who reduced their dose frequency to anywhere between every 10 days to every 5-6 weeks, 26 of them remained at the weight they had reached before doing so, and some even lost another couple of pounds, Mitch Biermann, MD, PhD, from the Scripps Clinic Department of Internal Medicine and the Scripps Whittier Diabetes Institute in San Diego, reported at the ObesityWeek annual meeting.

Patients also saw no subsequent worsening in blood glucose, lipids, blood pressure, or other metabolic measures, and some continued to improve.

“My main conclusion is that, at least among patients that experience normalized metabolic syndrome parameters doing every week on these medications, if they are that type of successful patient, they’re likely to remain successful even if you reduce the frequency,” Biermann said. “The dose doesn’t have to be the maximum, and the frequency doesn’t even have to be every other week.”

Patients are usually the ones to start the conversation about deescalation, Biermann said, sometimes before they even start the medication. When patients learn they may benefit from a GLP-1 agonist, “the first question I get, is not, ‘what are my risks of medullary thyroid cancer? What’s my risk of an [acute kidney injury]?’ It’s ‘how long do I have to be on this thing?'” he said. “People are pre-contemplating the change, and right now, we don’t really have a good answer for those patients.”

Two previous trials have shown that abrupt discontinuation often leads to weight regain, so reducing the frequency of the dose is a way to mitigate that risk while reaping the benefits of reduced medication costs or addressing a loss of payer coverage when patients have reached a weight they are comfortable with, he said.

Biermann said he approaches these decisions by assessing three things:

  • Does the patient want to deescalate?
  • Has the patient normalized their weight or otherwise reached a plateau?
  • Have most or all of the comorbidities associated with obesity improved or resolved?

“I actually recommend it more often when just two of these three things are true,” Biermann said, especially if there may be remaining comorbidities that are potentially due to another cause.

For the study, Biermann asked 34 patients who had approached him about reducing their dose frequency if they would like to start getting their dose every other week; all but four agreed. Participants were an average 59 years old with an average body mass index (BMI) of 30. The average tirzepatide (Zepbound) dose was 7.5 mg, and the average semaglutide (Wegovy) dose was 1.7 mg.

Four patients returned to weekly dosing after starting to regain weight. Of the remaining 16 men and 10 women, five took the medication every 10 to 14 days, 16 took the medication every 2 weeks, and five had more than 2 weeks between each dose.

Researchers measured the patients’ collective body fat percentage, body fat mass, skeletal muscle mass, and truncal body fat mass at three time points: before they started the medication, at their weight plateau when they switched to less frequent dosing, and then at the 38-week follow-up during reduced-dosing maintenance. The 26 patients experienced no significant change in those metrics after reducing their dose frequency.

Patients’ HbA1c, triglycerides, mean arterial pressure, systolic blood pressure, and diastolic blood pressure also did not significantly change after 38 weeks on the reduced-frequency dosing, and there was a significant improvement in HDL during the maintenance phase.

About 20% of patients had at least three comorbidities before starting a GLP-1 receptor agonist, which dropped to only about 5% at their plateau and none after reduced-frequency dosing; just over 20% had two comorbidities before taking a GLP-1 drug, which fell to a little over 10% after taking the reduced dose. All patients achieved healthy triglyceride levels during the maintenance phase, and more patients had healthy blood glucose and blood pressure ranges during the maintenance phase than at their plateau.

Sarah Barenbaum, MD, an assistant professor of clinical medicine at Weill Cornell Medical College and an assistant attending physician at NewYork-Presbyterian Hospital in New York City, was pleased to see the research.

“I think we need more studies like this to help guide clinicians,” Barenbaum told MedPage Today. “Clinical trials are so different from how we practice clinically,” and when patients do reach an ideal weight, the clinician and patient need to decide whether to remain on the medication, reduce the dosage, or reduce the frequency of doses. “We don’t do this universally,” she said. “It’s another off-label technique that we have that really helps patients.”

But it’s important to get data seeing what happens with those off-label practices, Barenbaum suggested.

“An important takeaway for clinical practice is just that there’s so many different ways to do this, and every patient is unique, and this really needs to be individualized,” Barenbaum said. “For some people, this is the right decision. For some people, it may not work. I think [Biermann] did a good job of pointing that out that this doesn’t always work for everybody, but for the right person, it can really help.”

In his presentation, Biermann highlighted a couple of individual patients’ specific progress. One 56-year-old woman had been taking a 5-mg dose of tirzepatide every 10 days for 115 weeks and went from a BMI of 29 before the medication to 25 at her plateau, and then to a BMI of 26 during the maintenance phase.

Biermann acknowledged several limitations to the data beyond it being a retrospective case series: the power was lower for comparing changes in comorbidities and body composition than for weight, four patients needed to return to weekly dosing because of weight regain, and no patients had class III obesity when they started taking a GLP-1 agonist. Also, the patients selected for deescalation were specifically those who had already been successful at losing substantial weight and improving metabolic parameters.

“I definitely counsel patients that this will not work for absolutely everybody, but for the vast majority of people, it seems to,” Biermann said.