Two new clinical trials suggest the strategy can be successful, whether that means switching to a lower-dose GLP-1 injection or pill.
“However people get their weight down, the body will fight to get it back up,” says Richard Siegel, MD, endocrinologist at Tufts Medicine Weight + Wellness – Stoneham, in Massachusetts. “There is a strong likelihood that the weight will trend back up unless people take action. Maintenance dosing is a big part of the plan that needs to be put in place.”
The right maintenance dosing “can look different for everyone,” according to Mir Ali, MD, medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, California. But the latest clinical trial results deliver a framework for healthcare providers and their patients.
Two GLP-1 Strategies Helped Lock in Weight Loss
The new studies, published in peer-reviewed medical journals within a day of each other, were funded by Eli Lilly, which makes the GLP-1 medications Zepbound (tirzepatide) and the oral drug Foundayo (orforglipron).
Dropping From a Higher to a Lower Dose of Tirzepadite
The trial looked at the safety and effectiveness of tirzepatide in two scenarios:
- Continuing to take tirzepatide at the maximum tolerated dose (10 or 15 milligrams [mg], depending on the patient) after initial treatment on that dose
- Lowering the dose to 5 mg after initial treatment to maintain weight loss.
The researchers compared both doses against a placebo.
Key findings:
Those Who Stayed on the Maximum Tolerated Dose After 60 weeks of weight loss on tirzepatide, people who stayed on the same dose during a maintenance stage (52 weeks) kept off all the weight (about 50 pounds).
At the start of the trial, they were 247 pounds, on average; by the end they were 197.
Those Who Dropped to a Low Dose for Maintenance Study participants who reduced their dose to 5 mg regained a relatively small amount of weight (12 pounds, on average) compared with the total amount they’d lost over the prior 60 weeks (almost 54 pounds).
At the start of the trial participants were 250 pounds, on average; by the end they were 208.
Switching From Injections to a GLP-1 Pill
The study found that weight regain was relatively minimal, whether subjects lost weight from injectable semaglutide (Wegovy) or tirzepatide.
On average, patients who switched from semaglutide to orforglipron regained about 2 pounds of the weight they lost over the course of a year (almost 42 pounds total). At the start of the study they weighed about 250 pounds, on average; by the end they were about 211.
Those who switched from tirzepatide to orforglipron regained about 11 pounds of the weight they lost on average over a year (almost 55 pounds total). At the start of the study they weighed about 255 pounds, on average; by the end they were about 211.
The Trials Add Data to a Practice Doctors Have Already Been Doing
Healthcare providers have been prescribing maintenance doses of GLP-1s for years, Dr. Ali says. But there isn’t a lot of data to suggest how much weight patients can expect to keep off using different medications.
“Maintenance dosing refers to continuing treatment after initial weight loss, typically at a lower dose or a different formulation, to help keep the weight off long-term,” explains Nicole Paolini Albanese, PharmD, clinical professor in the department of pharmacy practice in the division of education and teaching innovation at the University at Buffalo in New York.
Maintenance dosing is typically appropriate “when a patient has reached targeted clinical or individual weight loss goals and approached a plateau point where there is no active weight loss or weight regain,” says Gitanjali Srivastava, MD, medical director of Vanderbilt Obesity Medicine.
Doctors may use different strategies for maintenance dosing based on a patient’s budget and how they react to certain medications, Ali says. “Some will take medications less frequently, some may have a lower dose,” he says.
Dr. Srivastava notes that he has some patients who have had success maintaining their weight loss by taking a GLP-1 medication once every three months.
Patients May Have the Best Results Staying on These Medications
The trials specifically looked at weight loss results, but doctors say the findings suggest that staying on a maintenance dose of medication can support improvements in heart health and blood sugar management.
“The body is different now. Metabolism is more efficient, more effective. Energy regulatory pathways in the body have reset,” Srivastava says. But those health gains may be erased when someone stops taking medications altogether, Ali says.
Dr. Siegel recommends patients view maintenance dosing the same way they would consider ongoing medication for any other chronic condition. “Chronic diseases need chronic medication,” he says. “There are some people with diabetes or obesity who can maintain [health gains] with lifestyle. But others may need chronic medication.”
Study Limitations to Consider
The trials did not follow the patients beyond a year of maintenance dosing, making it difficult to know what would happen longer term. “While helpful, decades-long data would be much more important, and I’m sure they will continue to monitor these patients,” Dr. Albanese says.
The trial population was also limited to people who responded to the medications and tolerated them.
Finally, neither trial looked at lifestyle alternatives like adjusting diet and exercise. “The only comparator was placebo, and we already knew that stopping these medications would result in weight regain,” Albanese says.
Some Maintenance Doses May Be Cheaper Than Others
The trials didn’t address pricing, but Ali says it’s often a factor for patients on maintenance dosing.
“Cost usually depends on a patient’s insurance plan and how the patient is getting the medications,” he says. “If patients are paying out of pocket, usually the dose is not that big of a factor. If it’s a prescription, it could affect the copay to some extent, but every insurance is different.”
Pills like Foundayo may also be cheaper than injectables like tirzepatide, depending on insurance coverage, Ali says. However, he says there often is not a big change in price between a maximum tolerated dose of an injectable medication and a maintenance dose.
“People need to know that they have choices,” Siegel says. “Let your provider know your goals and your budget. Full conversations about your needs are going to be important so that all of the options that can aid in maintenance are out there.”