Tirzepatide

GLP-1 (glucagon-like peptide-1) drugs are continuing to become household names for weight loss. They activate a receptor that has potential effects extending beyond just managing weight, with benefits on blood sugar levels, as well as heart, kidney, and liver health. One of the newest approved options is tirzepatide. However, unlike GLP-1 drugs like semaglutide and liraglutide, it works slightly differently, making it one of the most effective weight-loss drugs on the market.

What Is Tirzepatide?

For many people who are prescribed tirzepatide, questions often arise about how it works and other key features. Before discussing it with a healthcare provider, it can be helpful to know its characteristics.

• Tirzepatide is a prescription medication (brand names Mounjaro and Zepbound) given as a subcutaneous injection once weekly and is currently used for type 2 diabetes, weight loss, and sleep apnea.
• Patients on tirzepatide lost an average of 15% to 21% after almost 17 months, versus 3% with placebo over the same time frame.
• Animal studies suggest tirzepatide can cause thyroid cancer. People with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) should avoid using tirzepatide, according to the FDA label. 
• Tirzepatide can slow the emptying of the stomach and decrease the absorption of oral drugs, which may cause various drug interactions.

It’s important to work with a healthcare provider before taking tirzepatide. They can determine how appropriate, safe, and effective it will be based on a person’s overall medical history. 

How Tirzepatide Works

Typical GLP-1 agonists like semaglutide and liraglutide only activate the GLP-1 receptor. While they’re still effective drugs for managing weight and blood sugar, tirzepatide is different. It activates both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors.

As a dual GIP/GLP-1 agonist, tirzepatide mimics key hormones to have different effects on bodily processes. While it has similar effects to GLP-1 agonists, the effects are generally stronger with tirzepatide.

FDA-Approved Uses & Who’s a Candidate

Tirzepatide was first approved by the FDA in 2022 under the brand name Mounjaro. Since then, it’s been approved for other indications under the brand name Zepbound. 

• Type 2 diabetes: Tirzepatide (Mounjaro) is approved to manage blood sugar levels in people with type 2 diabetes when used alongside a diet and exercise plan.  
• Chronic weight management: Tirzepatide (Zepbound) is approved to manage weight in people who are obese (body mass index, or BMI, of 30 or over) or overweight (BMI of 27 or over) with at least one weight-related health condition, such as high blood pressure or high cholesterol.
• Sleep apnea: Tirzepatide (Zepbound) is approved to treat severe obstructive sleep apnea (OSA) in people who are obese.

Keep in mind, this drug is not approved for type 1 diabetes or diabetic ketoacidosis (DKA). It also hasn’t been studied in patients with inflammation of the pancreas (pancreatitis). Tirzepatide should always be used with a reduced-calorie diet and increased physical activity. 

Based on animal studies, tirzepatide may cause harm to an unborn baby. Consult a healthcare provider before using tirzepatide while pregnant or breastfeeding. 

Dosing & Titration (Weekly Injection)

Tirzepatide is generally given as a single-dose pen or a vial that contains a liquid solution for injection. It’s injected just under the skin for best absorption. 

How Well Does It Work? (What the Trials Show)

Various clinical trials have been done with proven benefits seen with tirzepatide. The key trials involving tirzepatide are called the SURPASS (for diabetes) and SURMOUNT (for weight loss) trials. 

Tirzepatide Efficacy at a Glance

Trial	Population	Duration	Mean A1C Change	Mean Weight Change
SURPASS-1 (2021)	Type 2 diabetes, drug-naive	40 weeks	1.9% to 2.1%	7 to 9.5 kg (12 to 21 lb)
SURPASS-5 (2022)	Type 2 diabetes on basal insulin	40 weeks	2.1% to 2.4%	5.4 to 8.8 kg (12 to 19 lb)
SURMOUNT-1 (2022)	Obesity (no diabetes)	72 weeks	Not measured	15 to 26 kg (33 to 57 lb)
SURMOUNT-2 (2023)	Obesity and type 2 diabetes	72 weeks	2.1%	13% to 15%

While these trials have shown the effectiveness of tirzepatide in a controlled setting, real-world results may differ. That’s because tirzepatide doesn’t work the same for everyone and can also cause side effects that can make it hard to continue the drug. Some people also switch to a lower dosage as a form of maintenance treatment, which could lead to reduced weight loss effects. 

Safety, Side Effects & Warnings

Tirzepatide is considered a safe and effective medication. However, side effects are still possible. Some people experience mild side effects or none at all, while others experience more severe side effects, especially with higher doses.

The most common side effects of tirzepatide include:

• Nausea
• Vomiting
• Diarrhea
• Constipation
• Indigestion
• Stomach pain

More serious side effects may include:

• Pancreatitis
• Hypoglycemia
• Acute kidney injury (from dehydration)
• Severe stomach problems
• Vision problems (diabetic retinopathy)
• Gallbladder disease
• Lung aspiration during anesthesia
• Allergic or hypersensitivity reactions

Studies in mice have found that GLP-1 drugs may increase the risk of thyroid tumors. More recent studies in people taking GLP-1s haven’t shown a significantly higher risk. A doctor or healthcare provider may recommend avoiding it if there’s a history of thyroid cancer to be safe. 

Talk to a healthcare provider if side effects persist or worsen, especially if side effects are making it hard to keep taking the medication. A healthcare provider may recommend adjusting the dosage if that’s the case.

Drug Interactions and Special Populations

Tirzepatide slows how quickly oral substances are processed in the body. That means not only food but also medications taken by mouth. Therefore, tirzepatide could reduce the levels of many oral drugs, potentially making them less effective.

Examples of oral drugs to watch for before using tirzepatide include: 

• Warfarin: This anticoagulant or blood thinner has a narrow therapeutic index. Meaning, it needs to be a certain blood level in the body to be most effective for those prone to blood clots. Tirzepatide could reduce the absorption of warfarin, potentially leading to an increased risk of clots.
• Oral hormonal contraceptives: Tirzepatide has been shown to reduce the absorption of birth control pills like ethinyl estradiol and norgestimate. Women taking tirzepatide may want to switch to a non-oral method of contraception. Using a barrier method, such as a condom, may also be recommended for 4 weeks after starting treatment and for 4 weeks after each dose increase.

In addition to oral medications in general, tirzepatide can interact with certain diabetes medications. Those who take tirzepatide with insulin or sulfonylureas like glimepiride and glipizide may be at a higher risk of hypoglycemia. These medications may need to be taken at a lower dose before starting tirzepatide. 

Tirzepatide vs. Semaglutide (Wegovy/Ozempic): What’s the Difference?

Tirzepatide and semaglutide (known by the brand names Wegovy and Ozempic) are both used for type 2 diabetes and weight loss. They help reduce appetite and increase insulin release when the body needs it. The main difference is that tirzepatide is a dual GIP/GLP-1 agonist, while semaglutide is solely a GLP-1 agonist. 

Clinical trials suggest that tirzepatide is a more potent drug than semaglutide. Some studies have directly compared the two, with tirzepatide edging out semaglutide in terms of average weight lost. Still, they both cause similar digestive side effects.

Trial	Objective	Duration	Mean A1C Change	Mean Weight Loss
SURPASS-2	Compare tirzepatide to semaglutide for type 2 diabetes	40 weeks	2% to 2.3% with tirzepatide vs. 1.9% with semaglutide	7.6 to 11.2 kg (17 to 25 lb) with tirzepatide vs. 5.7 kg (13 lb)
SURMOUNT-5	Compare tirzepatide to semaglutide for weight loss	72 weeks	Not measured	20.2% (20 to 27 kg or 44 to 59 lb) with tirzepatide vs. 13.7% (13 to 18 kg or 29 to 40 lb)

In addition, tirzepatide and semaglutide are dosed differently. Although they’re both taken once weekly as a subcutaneous injection, tirzepatide is generally taken at a higher dose than semaglutide. For example, the maximum dosage of tirzepatide is 15 mg once weekly, while the maximum dosage of semaglutide is 2.4 mg once weekly.

Access, Cost, and Coverage

Another important factor to consider when taking tirzepatide is the potential costs. At this time, tirzepatide is only available as a brand-name drug (either Mounjaro for type 2 diabetes or Zepbound for weight loss or OSA). That means the costs are generally higher than generic medications.

Without insurance, the average retail price of tirzepatide could reach over $1,000 per month. As a result, this drug can often be inaccessible for some. The price can also change based on the dosage prescribed and the pharmacy. Note that new policies could cap the cost of GLP-1 drugs in the near future. 

For those with private insurance or Medicare, coverage for tirzepatide can vary. Many insurance plans may not cover tirzepatide for weight loss, although some may cover it for the treatment of type 2 diabetes. Some plans may have restrictions like requiring patients to try a different drug first before covering tirzepatide. They might also require prior authorization or documentation from a healthcare provider detailing why a patient needs tirzepatide before they cover it.

Compounded tirzepatide may be a cost-saving option for some patients. However, they still carry potential risks and should only be considered after consulting a trained healthcare professional. 

Practical Use: Lifestyle, Injection Technique, and Adherence

Tirzepatide is sometimes called a miracle drug, and for good reason, based on the researched benefits. However, it’s not perfect, and following specific guidelines is important to ensure it works best with less risk of severe side effects.

Think about the following lifestyle tips and discuss them with a healthcare provider while taking tirzepatide to get the most out of the drug:

• Eating a balanced diet: Even though using tirzepatide can decrease appetite, it’s still important to eat a balanced diet. Examples of diets to eat while taking tirzepatide include the DASH and Mediterranean diet. No matter the diet, getting enough protein, fiber, and other nutrients can all help promote lean muscle mass. 
• Exercising: Staying physically active is also crucial when trying to lose weight or manage blood sugar levels. Aerobic and resistance exercises can help maintain or build strength.
• Staying hydrated: Tirzepatide may cause fluid loss, especially if side effects such as vomiting or diarrhea occur. This could lead to dehydration, which could cause kidney problems if it’s severe. Drinking enough fluids throughout the day can help prevent this.
• Managing common side effects like nausea: Experiencing nausea can be uncomfortable, but it doesn’t have to be unmanageable. Many people find they’re able to reduce or control it by eating smaller, more frequent meals and avoiding greasy or fatty foods. 

Tirzepatide is effective when it’s taken at the appropriate dosage, but it might not work at all if it’s not being taken consistently. That’s why sticking to the treatment plan is key, especially when increasing the dosage. 

If side effects are becoming a burden, that’s a sign that it’s time to ask a healthcare provider about lowering the dosage or extending the time interval between dose increases. Instead of increasing the dose every 4 weeks, it might change to increasing it after 6 weeks. 

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