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By now, stories of people achieving their weight loss goals while taking Ozempic, Zepbound, or other GLP-1 receptor agonists abound—but that doesn’t mean everyone will shed pounds on these weight management drugs.
One clinical trial indicated that only about 86% of the more than 800 participants achieved “clinically significant” weight loss after taking semaglutide, sold under the brands Ozempic and Wegovy, for 68 weeks. That means a good portion of users did not.
“Each person responds differently to medications, and the degree of weight loss achieved with treatment can vary based on personal factors,” says Priya Jaisinghani, MD, a clinical assistant professor specializing in obesity medicine at the NYU Grossman School of Medicine.
GLP-1s—prescribed to manage weight for people considered obese or overweight, as well as to control other health conditions—are still relatively new, with the first one being FDA-approved for weight loss in 2014. Scientists are still trying to understand what makes them work better for some people than others.
Here’s what’s known about how GLP-1s help people lose weight, why they sometimes aren’t effective, and what to do if yours isn’t working as well as expected.
New obesity management medications promote weight loss by mimicking the hormone GLP-1—or both GLP-1 and another hormone, GIP—to stimulate insulin production and slow stomach emptying. This makes people feel fuller faster and continue to feel satiated for longer.
While a doctor should help you assess whether you are truly not responding to your GLP-1 (or your expectations are too high), experts said you might want to pay attention to some red flags.
One indication that your medication isn’t correctly working is if cravings, food noise, and eating control don’t change while taking a GLP-1, says Jamy D. Ard, MD, a professor at Wake Forest University School of Medicine who has studied the medications. “With effective treatment, people who have these symptoms will notice a meaningful improvement in the intensity and frequency of these symptoms,” he says.
Of course, your weight can also give you a clue. As a rule of thumb, you should see a loss of at least 5% of your body weight in the first 12 weeks of starting a GLP-1, Ard noted. “If this isn’t achieved, then we would say the patient does not have a treatment response, and this treatment is not likely to get them to their weight treatment goal,” he said.
But if you’ve lost an expected amount of weight and don’t continue to shed pounds, it could be that your medication is working, but you’ve simply hit a weight loss plateau. At some point, the rate of weight loss slows down and then stops—but your weight should remain steady while on the drug.
“A plateau can occur, but this does not necessarily mean the drug is ineffective,” says Fatima Cody Stanford, MD, an obesity medicine scientist at Massachusetts General Hospital Digestive Healthcare Center in Boston.
If you and your doctor have determined that your GLP-1 isn’t helping you lose as much weight as expected, there could be several reasons.
One is that your dose may not be high enough, Cody Stanford says. A recent study involving about 3,390 people taking semaglutide or liraglutide, another GLP-1 for obesity, found that participants who took high doses of their drug—1.7 milligrams (mg), 2.0 mg, or 2.4 mg of semaglutide, or 3 mg of liraglutide—lost more weight after a year compared to people taking lower doses.
“Increasing the dose of a GLP-1 can sometimes enhance weight loss or maintain consistent weight loss,” says Cody Stanford. “But this is not guaranteed.”
Aside from dosage, physical factors can play a role. The same study found that people with a higher body mass index lost more weight after a year. Furthermore, people with type 2 diabetes tend to lose less weight on GLP-1s compared to those without it, Jaisinghani notes.
Other barriers to weight loss include lifestyle habits, such as not exercising or routinely eating sugary or fatty foods.
Finally, “medication adherence can influence outcomes,” Cody Stanford adds. The drugs are only effective if taken consistently, and people who pause the medication may gain some weight back. GLP-1s can also cause gastrointestinal issues like nausea and vomiting, and some people may discontinue use due to side effects before achieving their weight loss goals.
If you’re not reaching your weight loss goals, your doctor may recommend tweaking your dosage and changing your diet and fitness routine.
“Optimizing your medications and lifestyle strategies may be necessary, as weight loss medications work best when combined with lifestyle modifications,” says Jaisinghani.
However, if you’re still not responding to the GLP-1, switching medication may be another option. While research has found that GLP-1s can effectively help people shed pounds, one study from July found that participants who took tirzepatide, sold under the brand names Zepound and Mounjaro, were two times more likely to experience a 10% weight loss and three times more likely to experience 15% weight loss within a year, compared to patients on semaglutide.
If switching medications doesn’t work, underlying genetic or biological factors may make achieving your weight loss goals challenging. In those cases, Vedala said she would suggest alternative weight loss therapies, such as developing a diet and exercise plan. Bariatric surgery, which involves reducing the size of the stomach and making alterations to the small intestine to limit caloric absorption, is also an option for some people.