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GLP-1 drugs like Ozempic and Wegovy can help most people lose weight, but they don’t work for everyone. Johnér/Offset Images
  • GLP-1 medications like Ozempic and Wegovy have gained popularity for their ability to help people lose significant weight.
  • Despite the rates of success, about 15% of people will not see clinically relevant weight loss.
  • Doctors say there are several reasons why GLP-1 medications may not work for you, but there are alternative options available.

Ozempic and Wegovy have been called game-changers for people living with obesity or overweight.

One 2021 clinical trial indicated that 86.2% of more than 800 participants achieved “clinically significant” weight loss after taking 2.4 mg weekly doses of semaglutide (sold under the brand names Ozempic and Wegovy) for 68 weeks.

As promising as those numbers look, they also mean that 13.8% of people did not see clinically significant weight loss.

Doctors say it’s essential for patients to understand they could fall into either camp — responder or non-responder— even though the data suggests it’s more likely a person will respond.

“As in any other category of medication, one type of prescription is not going to be the best fit for every patient,” says Dr. Meghan Garcia-Webb, MD, who is triple board certified in internal medicine, lifestyle medicine, and obesity medicine. “It’s also important that patients don’t pin all their health success on one medication.”

The reasons patients end up in the non-responder category can vary — and sometimes, there is more than one factor.

Dr. Michael L. Glickman, MD, explains that “success” on a GLP-1 medication is considered a body weight loss of more than 5% after three months of treatment.

“However, ideally in clinical practice, we hope to achieve at least 10-15% [bodyweight loss], which can lead to more meaningful metabolic health,” says Glickman, a triple board certified family medicine, lifestyle medicine, and obesity medicine physician and the founder of Revolution Medicine. “It can be a little unpredictable how someone will respond to a weight loss medication. Based on studies, every medication has a subgroup of ‘non-responders.’”

Why? These are the five reasons health experts say they see the most.

Lifestyle changes

Though sometimes an overlooked footnote, trials for semaglutide (like this one of more than 1,900 adults published in 2021) included lifestyle intervention for both the placebo and medication group.

“To see the best response to a GLP-1 medication, patients should generally follow the six pillars of Lifestyle Medicine,” Glickman says. Those pillars are:

  • Eating a plant-forward diet
  • Regular exercise
  • Managing stress
  • Avoiding substance use
  • Quality sleep
  • Maintaining strong social relationships with family and friends

Are these novel? No, but Glickman says they’re essential for people whether they’re trying to lose weight or not and can impede the effectiveness of anti-obesity medication.

A 2023 study pointed out another reason exercise is essential for people on weight loss drugs: When people lose weight, they can lose muscle mass.

Exercise can help mitigate that loss and its associated risks, such as injury.

Not taking medication as prescribed

Taking the correct dose regularly is important for success.

“If the medication is not taken as prescribed, such as missing doses or not following instructions on timing or dosage, it may not work effectively,” says Dr. Yoshua Quinones, MD, a board certified internist with Medical Offices of Manhattan and contributor to LabFinder.

The reasons for this issue vary, from poor education on how to take the medication to forgetfulness. Additionally, research suggests that people are more likely to lose weight if the drug is taken long-term.

A 2022 trial indicated that people regained two-thirds of their weight within a year of stopping 2.4 mg weekly doses of semaglutide. On a similar note, Quinones says people may not see weight loss at all if they start and then immediately stop.

“GLP-1 agonists often require a certain duration of treatment before their full benefits are achieved,” he says. “Premature discontinuation or non-adherence to the prescribed regimen could result in unmet therapeutic goals.”

Remember that the trials followed patients for over a year — 68 weeks.

A 2021 trial indicated that being a responder by week 20 was predictive of successful body weight loss of 15%, with more than 96% of those participants going on to lose weight.

In a Reuters report with analysis from pharmacy benefits manager Prime Therapeutics, only 32% of people said they were still taking Ozempic and Wegovy after one year.

Not everyone can afford to stay on the drugs long-term. The monthly cost of drugs like Wegovy can be around $1,000.

Insurance programs, including Medicare, do not always cover weight-loss drugs, and legislation to expand Medicare coverage to include anti-obesity medications has stalled, according to a Scientific American report. Even if people can afford the drugs, shortages have plagued patients.

Besides access – an important factor — patients may experience side effects like GI discomfort. For some, these side effects are enough to stop taking the medications altogether.

“The medication side effects often resolve with time, but if they are severe enough, some patients may decide it’s just not worth seeing what happens,” Garcia-Webb says. “The entire goal of these medications is to improve people’s health and quality of life, not require them to use all their sick leave.”

Other medical issues

A person may have other medical issues that are undiagnosed or going untreated or undertreated.

“Some medical issues — hypothyroidism, sleep apnea, chronic insomnia, to name just a few — can interfere with weight loss efforts and should be treated prior to starting a weight medication,” Garcia-Webb says.

Additionally, a person may have an eating disorder.

“For patients who have an obesity issue and binge eating disorder, sometimes the binge eating will correct itself with the GLP-1 agonist, but not always,” Garcia-Webb says.

A 2024 review indicated that small pilot studies suggest GLP-1s can reduce some eating disorders, but researchers said more rigorously collected data is needed.

Insulin resistance

Ozempic is designed to treat people with diabetes and help them lower their A1C. However, research, like a 2022 narrative review, indicates that people may lose less weight on GLP-1 medications.

“When there is already a pre-established metabolic disease, it becomes more of an uphill battle to reverse those abnormalities, especially if they have been established for a long time,” Glickman says.

The response is physiological.

“In patients with type 2 diabetes, the ability of their bodies to respond to GLP-1 and stimulate insulin secretion is reduced,” Quinones explains. “Usually, GLP-1 aids in controlling blood sugar levels by stimulating the pancreas to release insulin after meals. However, this response may be less potent than in individuals without diabetes. This weakened response to GLP-1 can make it challenging to manage blood sugar levels in patients with diabetes and may require alternative treatment methods or adjustments in medication dosage.”

Medication interference

People taking a GLP-1 drug with other medications may see less weight loss.

“Patients may also have a harder time losing weight if they are on certain medications at the same time as a GLP-1 that can promote weight gain, such as certain antidepressants and beta blockers,” Glickman says.

Garcia-Webb agrees and encourages people to speak with their providers about other medications they are taking before starting a GLP-1 medication and if they do not experience weight loss.

Importantly, patience is critical when taking a medication like Ozempic or Wegovy.

“Ideally, give the medication at least 12 weeks to see an effect,” Garcia-Webb says.

However, if you’re not seeing the needle move by that point or have concerns, experts say you have options.

Speak with your doctor

Experts stressed the importance of having an open dialogue with your doctor, whether the weight is coming off or not.

“Seeking guidance from a healthcare provider is essential,” Quinones says. “They can evaluate individual factors affecting effectiveness and suggest necessary adjustments, like altering doses or exploring alternative treatments.”

Garcia-Webb meets with patients at least once a month when increasing doses and more if the person has significant side effects. She encourages people to find providers who have regular follow-up plans.

Lifestyle tweaks

Collect some data on yourself.

“Are you optimizing your lifestyle changes, like stopping when full, eating mainly whole, unprocessed foods, cooking your own meals instead of eating takeout or delivery, drinking enough water, sleeping seven to hours a night, and exercising consistently?” Garcia-Webb suggests asking yourself.

If not, Quinones says adjusting habits, like managing portion sizes, can help. Additionally, stress can play into habits, from eating to sleep.

“Addressing emotional and psychological aspects is crucial,” he says. “Seeking assistance from a therapist, counselor, or support group can address issues such as emotional eating or stress management, thereby enhancing overall well-being and weight management progress.”

Manage side effects

Side effects can go away with time. However, Garcia-Webb says people can take some steps to mitigate and manage them, including:

  • Eating small, frequent meals.
  • Avoiding greasy foods, which sit in the stomach longer and may make GI issues like nausea and reflux worse.
  • Speaking with your doctor about over-the-counter and prescription medications that may help you manage side effects, potentially only on a short-term basis.

Switch to a different medication

Ozempic and Wegovy are not the only options for people. Zepbound was approved in 2023 for the treatment of obesity and overweight, as well as specific underlying conditions.

A 2023 trial indicated that people who were living with obesity or overweight without diabetes experienced a mean bodyweight reduction of 21% by 36 weeks.

Mounjaro, which uses the same ingredient (tirzepatide) and is made by the same company (Eli Lilly), is for people with diabetes.

Quinones says switching from Wegovy to Zepbound may be worth trying. The two drugs have distinctions.

“Wegovy, derived from semaglutide, acts as a GLP-1 receptor agonist, mimicking the GLP-1 hormone to reduce appetite by increasing insulin secretion and signaling feelings of fullness to the brain,” he says. “In contrast, Zepbound, a form of tirzepatide, operates as a dual agonist for both the glucose-dependent insulinotropic polypeptide (GIP) and the GLP-1 receptor, promoting insulin secretion and sensations of satiety. Both GIP and GLP-1 agonists are hormones naturally produced in our gastrointestinal system.”

Quinones says some people may experience more weight loss on Zepbound, including people not responding to Wegovy.

While many people will respond to Wegovy and Ozempic for weight loss, up to about 15% of people will not respond to the drugs.

The reasons vary, from the need to make lifestyle tweaks like diet and exercise to metabolic issues and side effects from other medications.

GLP-1 medications are best if taken long-term, but shortages, price, and side effects like GI discomfort are potential barriers for some.

Additionally, other medical issues may hamper weight loss. It’s important to discuss issues you are having with your doctor and that providers make plans for follow-ups. Your doctor may be able to help you manage side effects.

They may also refer you to specialists to treat other conditions and work with you to find medications for conditions like depression that do not typically list weight gain as a side effect.

Other drugs, like Zepbound, may be more effective for some patients.