Tirzepatide May Be Better For Weight Loss Than Semaglutide—But It's Complicated
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A lot has happened in the weight loss space over the last year, with a slew of medications suddenly becoming household names. With that, it’s more than fair to wonder what the deal is with tirzepatide vs. semaglutide.
On a basic level, tirzepatide is the generic name for Mounjaro, which is approved by the Food and Drug Administration (FDA) to treat type 2 diabetes, and Zepbound, which is FDA-approved for weight loss. Semaglutide is the generic name for Ozempic—FDA-approved for type 2 diabetes treatment—and Wegovy, a weight loss medication.
“Semaglutide and tirzepatide are very similar medications, but there are a few important differences,” says Dina Peralta-Reich, MD, director of New York Weight Wellness Medicine. If you’re interested in taking one of these medications, you’ll need to speak to a healthcare provider who should be able to guide you on next steps, including which one of these may be ideal for you.
Meet the experts: Kunal Shah, MD, is an assistant professor in the division of endocrinology at the Rutgers Robert Wood Johnson Medical Center. Dina Peralta-Reich, MD, is the director of New York Weight Wellness Medicine. Mir Ali, MD, is a bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, California. Steven Batash, MD, is a gastroenterologist and leading physician at the Batash Endoscopic Weight Loss Center.
It's true that one medication has consistently shown better weight loss results in studies (more on that in a sec), but doctors stress that doesn’t mean it’s the best—or most feasible—solution for everyone.
So, is tirzepatide or semaglutide better for weight loss? Here’s what you need to know.
What is semaglutide?
Semaglutide is the active ingredient in Ozempic and Wegovy. It’s an injectable medication in a class of drugs known as glucagon-like peptide 1 (GLP-1) agonists. These drugs help improve blood sugar and can lead to weight loss, explains Kunal Shah, MD, an assistant professor in the division of endocrinology at the Rutgers Robert Wood Johnson Medical Center.
Semaglutide mimics a protein in your body called GLP-1, and activates GLP-1 receptors in your body to increase the production of insulin, a hormone that helps escort glucose into your cells where it’s used for energy, Dr. Shah explains. Semaglutide also stimulates a pathway in your brain that controls your hunger cues and slows digestion. “That makes you feel fuller and less hungry,” Dr. Shah says.
What is tirzepatide?
Tirzepatide is the main active ingredient in both Mounjaro and Zepbound. It’s a type of injectable medication called a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist.
Tirzepatide works similarly to semaglutide but also targets an additional receptor—GIP —explains Mir Ali, MD, bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, California. “It works by helping you feel full and slowing the passage of food through the digestive tract which essentially reduces appetite,” says Steven Batash, MD, a gastroenterologist and leading physician at the Batash Endoscopic Weight Loss Center.
Because tirzepatide targets two receptors, it has the potential to give patients “an edge” over medications that only address one receptor, Dr. Batash says. Dr. Shah agrees. “Tirzepatide is a medication that basically builds off of what has already been done with semaglutide,” he says.
Do they both work for weight loss?
Yes, both medications work for weight loss. “Due to their effects on slowing gastric emptying, increasing satiety, and reducing appetite, both tirzepatide and semaglutide work for weight loss,” Dr. Batash says. “Both of these medicines decrease appetite and work best with diet and exercise to help you lose weight and keep the weight off in patients with obesity caused by certain conditions.”
Is tirzepatide or semaglutide better for weight loss?
“In studies, tirzepatide is better for weight loss,” Dr. Shah says. But he stresses that everyone responds to the medications differently. “I’ve had some patients respond better to semaglutide,” he says.
Let's look at the research: People who took the maximum dose of tirzepatide over 72 weeks lost an average of 21 percent of their body weight, according to data from clinical trials published in The New England Journal of Medicine in 2022. That was compared with a 3 percent loss in people in the placebo group. (Doses of Zepbound range from 5 milligrams to 15 milligrams.)
Research on the effectiveness of semaglutide has also been positive: 175 subjects with overweight or obesity who took semaglutide lost an average of 5.9 percent of their body weight after three months (13 weeks) and 10.9 percent after six months (26 weeks; at which points there were 102 subjects), a cohort study published in JAMA Network Open in 2022 found. Separately, over 200 subjects on semaglutide lost an average of 15.2 percent of their body weight after 104 weeks, per a study published in the journal Nature Medicine in 2022.
What other factors should you consider before going on tirzepatide or semaglutide for weight loss?
There are a few considerations. One is potential side effects: “They basically have the same side effects,” Dr. Shah says, noting that they’re mostly gastrointestinal things, like nausea and vomiting. These potential side effects also tend to get better once someone has been on a dosage for a while, he says.
“We do have more years worth of data with semaglutide—it’s been out longer,” Dr. Shah says. “If someone is anxious about potential long-term side effects, I’ll often prescribe semaglutide because of this.”
Health insurance coverage and cost is also a huge factor, Dr. Ali says. “Tirzepatide costs more—even the generic version costs more,” he says. While tirzepatide has been on the market to treat type 2 diabetes under the name Mounjaro, Zepbound was just FDA approved for weight loss and most health insurances don’t cover it as a result, Dr. Ali says. These medications can be $1,000 or more a month without health insurance, making coverage crucial for many patients, he says.
“There may also be a supply issue,” Dr. Ali says. Semaglutide has been in shortage for months, which can make it difficult to effectively prescribe it to patients, he points out. However, tirzepatide is also currently in shortage—access may ultimately depend on what’s available in your area.
Each medication may also have contraindications with underlying health conditions you may have or other medications you may be taking, Dr. Ali says. With that, it’s really best to talk to your doctor to see whether one or the other may be better for you.
If you qualify for either medication and can afford it, doctors say they’re worth considering. “They can be life changing,” Dr. Peralta-Reich says.
Bottom line: If you’re interested in taking a weight loss medication like semaglutide or tirzepatide, talk to your doctor. There are a lot of factors to consider with each, and your healthcare provider can help you wade through it all.
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