People who reach a healthy weight and improve their metabolic health on GLP-1 medications may be able to maintain those gains even if they cut back on their dose by switching from weekly to every other week, according to preliminary research.
These findings could have a major real-world impact, says the senior author, Mitch Biermann, MD, PhD, an obesity medicine and internal medicine doctor at Scripps Clinic Carmel Valley in California.
“The number one concern I get from patients who are hesitant to start therapy is that there is no way to de-escalate therapy once they lose weight. This data provides examples of an approach that is often highly successful, which can motivate people to begin in the first place,” says Dr. Biermann.
More Than 3 Out of 4 People Stayed at Their Maintenance Weight After Switching to 1 Shot Every 2 Weeks
The research was a retrospective chart review, meaning investigators looked back at medical records rather than enrolling participants in a randomized controlled trial. The study was small: It included just 30 patients from a primary care obesity medicine practice who had reached a normal weight or resolved their weight-related health conditions after being on a weekly GLP-1 therapy, in this case either Ozempic (semaglutide) or Zepbound (tirzepatide).
Most people were on less than the maximum recommended dose on a weekly schedule for 38 weeks before they switched to every other week. With regular dosing, people lost an average of about 15 percent of their body weight. The average BMI dropped from 29.5 to 24.5.
Here are the key findings from the analysis.
- Weight and fat-versus-muscle ratio stayed about the same. After switching to every-other-week injections, people lost an additional 2 to 4 pounds (lb) on average, and body fat loss improved slightly but stayed about the same.
- Metabolic health stayed stable. Improvements in blood sugar control, triglycerides, and systolic blood pressure stayed about the same after the reduced dosing.
- Most participants kept the weight off. Only 4 of the 30 people regained weight and chose to return to weekly dosing.
The other 26 people continued to maintain their results with reduced dosing, with some people opting to stretch their dosing schedule even longer than two weeks.
In Practice, Some Doctors Are Already Helping Patients Taper Off GLP-1 Dosing
Like many healthcare providers who prescribe GLP-1s, Yuval Pinto, MD, has de-escalated dosage frequency with patients who want to try it.
“It can be effective, and the findings presented here are promising,” says Dr. Pinto, an obesity and family medicine doctor at Johns Hopkins Medicine in Baltimore, who wasn’t involved in the research. “But because the study involved a small number of people and the findings are from a retrospective chart review rather than a randomized study, they should be viewed as preliminary.”
There are so many factors that impact weight, Pinto says. Taking a medication like a GLP-1 is one, but other drugs, conditions like sleep apnea, and diet and exercise can make a difference, too. This study didn’t account for those factors, he points out.
The finding that the majority of people were able to maintain their weight was “slightly surprising,” says Peminda Cabandugama, MD, an endocrinologist and obesity medicine specialist at Cleveland Clinic in Ohio.
“The pharmacokinetics [how drugs move through the body] of GLP-1 medications show a half-life of 5 days, which means the current standard of using these medications every 7 days is also stretching this out,” says Dr. Cabandugama, who wasn’t involved in the study. Half-life is the amount of time it takes for the drug’s initial concentration in the body to decrease by half.
The findings also could be influenced by the small number of people in the study, he adds.
“Whether or not people can successfully de-escalate could be related in part to how they metabolize the drug and the length of that ‘steady state,’” Pinto says. That can vary from person to person depending on age and how well their liver and kidneys are working.
Larger Studies Are Needed
There are a “very small number” of people who stop taking GLP-1s and don’t regain the weight they lost, but those people are the exception, says Pinto.
If these new findings are confirmed in larger studies, it could help some people stay on GLP-1s longer and maintain a healthy weight, he theorizes, if it meant they could make these expensive prescriptions last longer.
“The common narrative among all medical societies is that you need to take these medications indefinitely, which in real life is not an option for most people. At some point insurance would discontinue them,” he says.
“The average time that a person stays on a GLP-1 in the U.S. is a year and two months,” he says.
Lifestyle Factors Like Exercise May Help People Reduce Medications
Weight loss efforts are best maintained when people exercise frequently, says Biermann.
“We have a national survey of people who keep weight off for many years called the National Weight Control Registry, and the average people exercise in that group is an hour a day,” he says.
“I also have patients who use the medicine even less often than every two weeks, and they uniformly tell me they are exercising a lot as well,” says Biermann.
Thinking About Spacing Out Your GLP-1 Injections? Here’s What to Do
The experts all agree: If you want to make any changes in the dose or frequency of your GLP-1, you need to talk to your healthcare provider first.
“There’s no standard of care for how to de-escalate therapy, and so different physicians have different experiences and practices,” says Biermann.
People taking a GLP-1 who want to adjust their dosing for whatever reason — finances, changes in insurance coverage, or they no longer want to be on the medication — should talk with their doctor about the best path forward, says Pinto.
When Pinto has a patient who asks about weaning off their GLP-1 or spacing out dosing, he is very receptive to the conversation. “Patient-centered medicine is the best medicine,” he says.
First he’ll review with his patients what their goals were and what they’ve accomplished so far. “Let’s see if we were able to reverse your prediabetes. Did we improve your fatty liver, your sleep quality, your exercise, your diet?”
If the patient has improved their metabolic profile and reached a healthy weight, “I’m game,” says Pinto. After the new dosing schedule is agreed upon, he continues to monitor their weight and muscle mass.
“If after a few months the patient increases muscle mass and their weight doesn’t change, amazing, right? If there is a rebound weight, we have a problem, because we’re going to create the same problems that we started with,” says Pinto. Working with your provider, he says, can keep you on the right track.
