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semaglutide versus tirzepatide for weight loss: two adults exercising outside

What’s The Difference Between Semaglutide And Tirzepatide For Weight Loss?

If you haven’t heard about prescription drugs like Ozempic® and Mounjaro™ at the doctor’s office, you’ve surely seen them in news headlines. In recent years, an increasing number of Americans have been turning to prescription drugs to help curb obesity, treat type 2 diabetes, and achieve dramatic weight loss.

Many medical professionals believe that these medications can be game-changers for patients, especially given the stark reality that more than two in five U.S. adults have obesity and about one in 10 (38 million) Americans have diabetes. Changes in food quality (most notably sky-rocketing consumption of processed foods), dramatic increases in portion sizes, and more sedentary lifestyles have contributed to these health concerns, explains internal medicine physician and weight loss specialist Dr. Justin Zaghi, M.D., founder of Shapely. And many patients struggle to make strides against them.

Before medications like Ozempic® and Mounjaro™ hit the scene, the best medications available for supporting weight loss were stimulants like phentermine, Zaghi explains. Not only were these less effective but they also came with potential side effects, such as dry mouth, heart palpitations, insomnia, and irritability. 

Although Ozempic® and Mounjaro™ are often lumped together in conversation (they do both show promise for supporting weight loss), they belong to distinctly different types of drugs and have unique mechanisms of action. Here’s what to know about semaglutide (like Ozempic®) and tirzepatide (like Mounjaro™)—including how to suss out which might be a better fit for you.

  • ABOUT OUR EXPERTs: Dr. Justin Zaghi, M.D., is an internal medicine physician, weight loss specialist, and the founder of Shapely. Kiera Lane, N.M.D., MSAc, L.Ac., Dipl. Ac., is a naturopath and the director of Arizona Natural Medicine. Mohit Joshipura, M.D., a board-certified internal medicine physician who specializes in weight management, is a member of the Whole Health Rx Medical Advisory Council

What is semaglutide? 

Semaglutide, made by Novo Nordisk under the trade names Wegovy®, Ozempic®, and Rybelsus®, belongs to a class of medications called glucagon-like peptide-1 (GLP-1) receptor agonists. It works by mimicking the effects of a naturally occurring hormone called GLP-1, which helps regulate blood sugar levels, appetite, and body weight, explains naturopath Kiera Lane, N.M.D., MSAc, L.Ac., Dipl. Ac., director of Arizona Natural Medicine. 

“Semaglutide stimulates the process of insulin secretion in the body, slows gastric (stomach) emptying, and promotes feelings of fullness, leading to reduced food intake and weight loss,” Lane says. 

Ozempic® is an injectable medication that’s FDA-approved for lowering blood sugar in adults with type 2 diabetes—and to reduce the risk of stroke or heart attack in patients who have both type 2 diabetes and heart disease. Wegovy® is also an injection but is instead approved for adults and older children with obesity and overweight adults with weight-related medical issues. Meanwhile, Rybelsus® is an oral medication FDA-approved for managing blood sugar in adults with type 2 diabetes. Although only Wegovy® is approved specifically to support weight loss, the others are often used off-label for that purpose. (This means that the FDA hasn’t deemed them safe and effective for weight loss, though it’s legal for providers to prescribe them for such.)

“Oral semaglutide is taken daily, whereas injectable semaglutide is administered weekly,” says board-certified internal medicine physician and member of the Whole Health Rx Medical Advisory Council Mohit Joshipura, M.D., who specializes in weight management. “Currently, it is accepted that oral semaglutide is less effective than injectable semaglutide from a weight loss standpoint.”

Read More: How To Fill Nutritional Gaps If You’re Taking A GLP-1 Weight Loss Drug

In general, research has shown promising results for semaglutide. In fact, one The New England Journal of Medicine study on 2,000 obese adults found that half lost 15 percent of their body weight while nearly a third lost 20 percent of their body weight after 68 weeks of using injectable semaglutide along with a diet and exercise program.

Common side effects of injectable semaglutide include nausea, vomiting, diarrhea, abdominal pain, and constipation. Some people may also experience less common side effects like anxiety, blurred vision, dizziness, or a skin rash. Other, more serious risks include the development of tumors of the thyroid gland, including medullary thyroid cancer.

What is tirzepatide? 

Tirzepatide was developed by Eli Lilly and Company and goes by the trade names Mounjaro and Zepbound. Mounjaro™ was approved by the FDA first for the treatment of type 2 diabetes, and Zepbound™ was later FDA-approved for the treatment of obesity. Tirzepatide belongs to a class of drugs known as dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists, explains Zaghi. Unlike semaglutide, it has two pathways of action. 

“Tirzepatide works by stimulating the release of GIP and GLP-1, two hormones that play key roles in regulating blood sugar levels, appetite, and body weight,” Zaghi says. “By activating both GIP and GLP-1 receptors, tirzepatide helps lower blood sugar levels, improve insulin sensitivity, reduce appetite, and promote weight loss.” 

As such, tirzepatide appears to be even more potent from a weight loss perspective than semaglutide, according to Joshipura. (A recent study published in Diabetes, Obesity and Metabolism backs this up.) “Additionally, potentially because the GIP component may have an anti-nausea impact on the CNS (central nervous system), tirzepatide can be better tolerated by patients, as well,” he adds.

Read More: Research Confirms The Best Time To Work Out For Weight Loss

Research has also shown promising results for tirzepatide in lowering blood sugar levels and improving glycemic parameters and lipid levels—in addition to promoting weight loss—in patients with type 2 diabetes and obesity. 

Both tirzepatide drug options are administered once weekly and are injected into a fatty area such as the abdomen or thigh. Common side effects while taking tirzepatide include nausea, diarrhea, absence of appetite, vomiting, constipation, and indigestion (also acid reflux). More serious side effects include pancreatitis, gastroparesis, and diabetic retinopathy. Additional risks include gallstones and certain cancers like pancreas, thyroid, breast, liver, and colon.

which Route is best for you?

When determining which medicine might be best for you, there are a few factors to consider. Among them: potential side effects (which largely overlap between semaglutide and tirzepatide), insurance coverage and cost, and supply chain dynamics (given that demand currently for these medications outweighs supply), explains Joshipura.

Cost and medication availability can often make your decision for you. In general, tirzepatide drugs are slightly more costly than semaglutide drugs. Your provider should be aware of all these moving pieces, pros, and cons—and can use that knowledge to prescribe accordingly. 

Since various semaglutide and tirzepatide drugs are FDA-approved for different uses and populations, it’s crucial to share a detailed medical history with your provider so they can consider your unique needs. (Interested in trying GLP-1s? Take the questionnaire at Whole Health Rx to see if you qualify.)

Zaghi recommends speaking to a provider specializing in weight loss and/or type 2 diabetes, as there are important intricacies about the medications that many doctors may not be aware of. “For example, tirzepatide can reduce the effect of birth control pills, and someone may unknowingly take the medication without being aware of that risk,” he says. “Providers specializing in weight loss can also identify medications that may be inadvertently contributing to weight gain, such as Benadryl, steroids, and antidepressants.”

It’s also worth pointing out that, while both of these drugs have been shown to induce rapid weight loss, a large percentage of the weight loss may come from muscle. “In order to combat muscle loss—and ultimately a depression of your metabolism—you must consume elevated amounts of protein and do regular strength training,” Zaghi says. He recommends that anyone taking semaglutide or tirzepatide consume no less than one to 1.2 grams of protein per kilogram of body weight (that’s 0.45 to 0.5 grams per pound) and perform resistance training at least three times per week to protect muscle as much as possible.

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