GLP-1 drugs like Wegovy and Zepbound have skyrocketed in popularity over the past few years, hailed as game-changers in the fight against obesity. Clinical trials showed impressive results: semaglutide users lost up to 14.9% of their body weight in just over a year, while tirzepatide users shed as much as 20.9%. But once these drugs left the clinical bubble and entered the real world, their performance became less predictable.
A new study published in Obesity followed nearly 7,900 GLP-1 users across Ohio and Florida who were overweight or obese but did not have type 2 diabetes. Most were white women with private insurance. After one year, the average weight loss was significantly lower than trial numbers—7.7% for semaglutide and 12.4% for tirzepatide.
Dr. Hamlet Gasoyan, a researcher at the Cleveland Clinic and the study’s lead author, believes the explanation is simple: “Roughly half of the patients stopped taking their medications within the first year. And 80% were on doses lower than what we see in clinical trials.”
That tracks with what 32-year-old Jessica from Miami experienced. She started semaglutide full of hope after seeing celebrities post dramatic before-and-after photos. “At first it worked. The pounds were dropping. But I constantly felt nauseous,” she shared on her Instagram. “I reduced the dose, but that also reduced the effect. Eventually, I just gave up.”
Jessica is not alone. In the study, around 22% of semaglutide users and 16% of tirzepatide users quit during the first year. After 12 months, another third dropped out. Those who stopped within the first three months lost only 3.6% of their body weight. Those who stayed on for up to a year lost about 6.8%.
The reasons? Cost, insurance issues, and side effects, according to Dr. Gasoyan. Dr. Osama Hamdy from Harvard Medical School also pointed to another problem: drug shortages. “During the study period, discontinuation rates were nearly three times higher than what we see in clinical trials.”
Another issue is dosage. Clinical trial participants received 2.4 mg of semaglutide or 15 mg of tirzepatide. But most real-world users stuck to lower maintenance doses—usually under 1.7 mg for semaglutide and under 10 mg for tirzepatide—largely because they couldn’t tolerate the full dose.
“Many people just can't handle the higher doses,” explained Dr. Richard Siegel, co-director of the Diabetes and Lipid Center at Tufts Medical Center. “The side effects are a dealbreaker for a lot of patients.”
That said, those who could stick to the full dosage did see similar results to clinical trial participants. One patient, George, a 58-year-old from Cleveland, followed his doctor’s and nutritionist’s guidance, gradually increasing his dose. After 13 months, he had lost nearly 14% of his body weight and brought his blood sugar down from prediabetic levels to normal.
The study found similar patterns: those who took higher doses and didn’t discontinue early were far more likely to achieve at least 10% weight loss. Beyond the numbers on the scale, some even reversed signs of prediabetes—a significant metabolic win.
Still, focusing too much on percentages can miss the point. Dr. Amy Rothberg from the University of Michigan said, “People obsess over how much weight they can lose. But even a 5% reduction can significantly improve health outcomes. That’s what we’ve seen in diabetes prevention trials.”
So what’s the best way to maximize results with GLP-1 drugs? For starters, patients should work closely with a care team to manage side effects, insurance hurdles, and lifestyle changes. “If side effects are manageable, slowly increase the dose,” advised Dr. Babak Orandi of NYU Langone Health. “But also prioritize healthy eating and physical activity.”
He recommends eating slowly, eating smaller portions, and avoiding greasy or fatty foods—especially during dose increases.
Ultimately, GLP-1s work best when they’re just one piece of a broader plan. Health providers can help secure insurance pre-authorizations, while nutritionists and behavior experts can guide long-term changes in eating and exercise habits.
Perhaps the most important point? The weight won’t stay off unless the habits do. “People who stop GLP-1s without making lifestyle changes are almost guaranteed to gain the weight back,” said Dr. Rothberg. “It’s not a magic fix. It’s a jumpstart.”
So before you pin all your hopes on a weekly injection, it’s worth asking yourself: are you ready for the work that comes after the weight starts to drop?