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Ozempic, Wegovy and newer GLP-1 agonists like Mounjaro, have become all the rage for weight loss. But there are big drawbacks to these medications that even doctors admit.
One is their estimated $1,400-a-month price tag, which isn’t covered by all insurance plans. Another is their black box warning that cautions the drugs caused thyroid cancer in rodents (though the same hasn’t been reported in humans). And people who stop taking these drugs often regain the weight they lost — plus more.
Then there’s a side effect that no one seems focused on….
The GLP-1 Agonist Plateau
GLP-1 agonists are synthetic versions of glucagon-like peptide 1 (GLP-1), a hormone made in the gut that controls blood sugar and insulin levels, as well as influencing hunger and satiety centers in the brain.
When these drugs are used to control weight, they work… for a while. But at some point, people hit a point where their weight stabilizes. And that plateau can differ for each person.
What’s more, sometimes with stabilization comes the return of appetite, which is something the drug is supposed to control.
On average, the plateau comes a little over a year with semaglutide, the active ingredient in Ozempic and Wegovy. In the STEP 1 and STEP 2 studies, participants’ weight loss gradually stopped after week 60 of the 68-week trial, with about 10 to 15 percent of body weight lost. In a longer 2-year study, STEP 5, patients plateaued at around 60 weeks, though they were able to maintain their weight for the rest of the study.
With tirzepatide, the active ingredient in Mounjaro, the plateau hit within 60-72 weeks. A 2-year trial of the drug is ongoing and expected to offer more insight.
While physicians aren’t surprised by this plateau, they say their patients often are upset by it.
“Everyone will plateau, of course. No one on my watch has disappeared. No one has vanished,” Dr. Jody Dushay, an endocrinologist at Beth Israel Deaconess Medical Center in Boston, tells MedPage Today. “It’s alarming to me that people find that surprising, but everyone will reach a plateau and there’s no way to know when you start the medication what that will be, what percent weight loss that will be, and how quickly they will reach it.”
Different responses for different patients
Dushay notes the importance of providers setting expectations with patients before prescribing GLP-1 agonists for weight loss. It’s also important to note that different medical histories, medications, and comorbidities can all affect how well, and for how long, an individual responds to these drugs.
Dushay says a “drug holiday,” where a patient stops and restarts a GLP-1 agonist has typically had no impact on plateaus.
Dr. Fatima Cody Stanford, an obesity medicine specialist at Massachusetts General Hospital in Boston, tells MedPage Today she would like to see future studies on GLP-1 agonists that stratify patient response by various characteristics like genetics. Right now, she notes, weight-loss drugs require a lot of trial and error, so predicting how likely success will be would save time and money.
“If I know that, on average, this person is going to be a really poor responder to a GLP-1 agonist, I won’t [prescribe it],” she says. “It is a really arduous pathway for a lot of reasons — access, coverage, prior authorization. It’s burdensome on the patient, it’s burdensome on the system, it’s burdensome on me.”
In the meantime, physicians do have strategies to help a patient move past a plateau if they still haven’t met important clinical markers. Some will increase the dose if the patient can tolerate it well, or they may supplement with a second drug that targets a different neuronal or hormonal pathway.
Natural alternatives to GLP-1 agonists
Are there any natural ways to get the same effects provided by these expensive, potentially toxic drugs? One has become known as “nature’s Ozempic” — berberine. This plant-based compound has been shown to help manage blood sugar, reduce cholesterol, and help with weight loss.
Another natural alternative, the humble chia seed, may also help reduce blood sugar and promote a feeling of fullness, keeping you from overeating. You could also try black seed oil, which has similar effects on blood sugar and could help manage obesity.
Finally, make sure your diet is rich in protein and soluble fiber, both of which can help with weight loss and blood sugar stabilization.
And remember, nothing beats diet and exercise. The best diet for weight loss is one you can stick to—and this one comes out on top!
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The GLP-1 Agonist Plateau No One’s Talking About — MedPage Today
Semaglutide Shines as Weight Loss Therapy — MedPage Today
Another Weight-Loss Trial Win for Weekly GLP-1 Drug — MedPage Today