Tirzepatide vs. semaglutide for weight loss

Effectiveness of tirzepatide vs. semaglutide

“Both medications are powerful in terms of helping people with obesity and those who are overweight who have weight-related health conditions achieve meaningful weight loss compared to lifestyle changes alone,” said Dr. Richa Mittal, an obesity medicine doctor and owner of Radiant Health Weight Loss and Wellness in Frisco, Texas.

Tirzepatide has been shown to help people lose more weight compared to semaglutide at the dosage regimens currently available, according to Mittal. In the 2022 clinical trial, tirzepatide showed more weight loss in the treatment group than in the placebo group at three different doses:

• 15% weight loss at the lowest weekly dose of 5 mg
• 19.5% weight loss at 10 mg
• 20.9% weight loss at 15 mg

In a study looking at semaglutide, those who took a weekly dose of 2.4 mg for weight loss only — not for those with diabetes — lost an average body weight of 14.9% compared to the 2.4% in the placebo group that only made lifestyle changes.

While people lost more weight on tirzepatide than semaglutide, it’s still a significant amount of weight, since research considers effective weight loss of more than 5% of body weight after 12 weeks of being on a weight loss medication.

Effectiveness for long-term use

Mittal says both medications are also effective for long-term weight loss, but are meant to be used on an ongoing basis for maintenance. A 2022 study showed when semaglutide is stopped, participants regained two-thirds of the weight they lost within one year and maintained about 5.5% of their weight loss.

Weight regain is a concern with stopping tirzepatide as well. According to a 2023 study looking at effects on weight maintenance, after 36 weeks, those who stopped tirzepatide had a 14% weight regain over the span of one year compared to those who remained on the medication and lost an additional 5.5% of their weight.

“Based on prior studies on weight loss medications, people using medication will achieve more weight loss than intensive lifestyle changes alone and also require ongoing treatment to maintain their weight loss,” added Mittal.

Side effects of tirzepatide and semaglutide

When comparing both tirzepatide and semaglutide for which medication is best for weight loss, side effects are an important consideration. Since both are GLP-1 receptor agonists, they have similar side effects, especially gastrointestinal (GI) ones, explains Thomas So, senior manager of the Consumer Drug Information Group at First Databank, which provides drug information to health care providers.

But tirzepatide is also a glucose-dependent insulinotropic polypeptide (GIP) receptor agonist. GIP is a gut peptide, just like GLP-1, but So says there are differences in these side effects and how often they occur.

Common GI side effects

So says GLP-1 medications such as tirzepatide and semaglutide can cause gastrointestinal (GI) side effects, such as:

• Nausea
• Diarrhea
• Vomiting, which can be more severe at higher doses
• Constipation, which is more common with semaglutide than tirzepatide

These side effects are more common when you first begin a GLP-1 medication and can worsen in the first few weeks, according to So. But after six to eight weeks of use, most people adjust and these symptoms improve.

Other side effects

While gastrointestinal side effects are most common, GLP-1 medications can cause other side effects, including:

• Gallbladder issues
• Temporary hair loss
• Low blood sugar, especially when combined with insulin or other diabetic medications
• Pancreatitis, which rarely happens

Cost comparison of tirzepatide vs. semaglutide

At the time of publication, semaglutide costs $1,349 for a month's supply without insurance. Tirzepatide is slightly less expensive at $1,086 for a month’s supply.

Generally, unless you’re prescribed GLP-1 medications for another health condition, such as diabetes, insurance doesn’t provide coverage, including Medicare and Medicaid. For some insurance policies, your health care provider needs to send in a prior authorization to cover certain weight loss medications.

So while you may not be able to rely on insurance coverage for GLP-1 medications, So explains you may be able to use savings cards and patient assistance programs.

• Novo Nordisk, which manufactures semaglutide, has a patient assistance program that provides free medication to eligible patients. It also provides savings cards for semaglutide that provide discounted prices for patients.
• Eli Lilly, the maker of tirzepatide, has a patient assistance program that provides medication for up to 12 months free of cost to those who are eligible. The company also makes a savings card for tirzepatide that provides financial and insurance assistance by lowering your out-of-pocket costs.

Purchasing compounded GLP-1 medications

Be cautious of purchasing GLP-1 medications online. “Because of recent national drug shortages for both tirzepatide and semaglutide, the FDA has allowed compounding pharmacies to compound these GLP-1 medications,” explains So. But this can come with concerns.

So says because these compounded medications aren’t regulated by the FDA, they can vary in potency, purity and safety. The National Association of Boards of Pharmacy (NABP), which helps enforce safety standards for medications, identified over 40,000 online pharmacies that are using illegal or questionable practices.

For those who still choose to use a compounded version of tirzepatide or semaglutide, So recommends the following:

• Verify the pharmacy’s accreditation: You can use the NABP’s Safe Site Search Tool to find out if an online pharmacy is accredited or not. It's also a good idea to check the FDA’s website to make sure the pharmacy is licensed in your state.
• Ensure the compounder does quality and sterility testing: This makes sure the products aren’t contaminated with harmful microbes.
• Avoid online sellers that don’t require a prescription: The FDA has a list of what to look for additionally before ordering medications online.

Choosing between tirzepatide and semaglutide

There are many factors to consider when making decisions about using weight loss medication, according to Mittal, such as:

• How much weight you want to lose: The average weight loss at different doses of tirzepatide is higher than the average loss on the highest dose of semaglutide.
• Cost of medications and your insurance coverage: Both of these medications are costly and often the choice between the two may depend on insurance coverage.
• Severity of side effects: People respond differently to the medications in terms of side effects, requiring switching from one to the other.
• If you take other medication: Your health care provider may need to adjust your dosages of blood pressure and blood sugar medications to avoid low blood pressure and low blood sugar.
• Lifestyle considerations: It’s important that even when taking tirzepatide or semaglutide, you still receive guidance from your health care team on nutrition habits, exercise, sleep and stress management. This can help achieve and maintain long-term weight loss, maintain muscle and manage side effects.

Some current health conditions can impact the choice between medications, says Mittal.

• Heart conditions: Semaglutide has been shown to reduce the risk of heart attack and stroke by 20% in those at higher risk. If you have a history of heart problems and have obesity, semaglutide may be the best choice. Both of these medications can also improve blood pressure and high cholesterol, according to research.
• Sleep apnea: Tirzepatide is FDA-approved for the treatment of obstructive sleep apnea, a condition where your breathing stops and starts throughout the night. If you have sleep apnea along with obesity, your health care provider may recommend tirzepatide.
• Prediabetes: If you have prediabetes, you might benefit from a GLP-1 type of medication like tirzepatide or semaglutide because, in addition to body fat loss, the medication helps with blood sugar control.

Working with a health care professional

“When looking for a weight loss provider, it’s useful to find a provider who has received additional training as a member of the American Board of Obesity Medicine,” explained Mittal. Any primary care provider can prescribe and manage weight loss medications, but weight management practices that focus on weight loss medications as a specialty will often be able to offer more counseling on behaviors and lifestyle to get you the best results.

Weight management practices are also knowledgeable about how to navigate insurance plans for medication coverage, according to Mittal.