Q: Tirzepatide pros and cons

Pros It’s a proven method for medically assisted weight loss. “For people who are dieting and exercising and losing a little weight or none at all, this medication really kickstarts things moving in the right direction,” says Dr. Richland. In clinical trials, tirzepatide was found to be effective and safe, with no major adverse events. Weight-loss drugs like tirzepatide don’t outperform bariatric surgery, but they spur greater and more sustained weight loss than any prior medication. Losing weight can have big health benefits. "Many patients are seeing improvement in blood pressure, lipid [cholesterol] levels, cardiovascular disease, and glucose levels,” says Dr. Richland. Cons Both brand-name and compounded forms of tirzepatide can be expensive, and health insurance may not cover it. As with all medications, side effects can occur. The most common are gastrointestinal-related and include nausea, constipation, diarrhea, and heartburn. These mostly occur when the dose of tirzepatide is increased; slowly increasing the dose usually helps reduce them. Other side effects include injection site reactions, hypersensitivity reactions, and fatigue. The drugs are administered via a weekly injection. You’ll either need to get comfortable injecting it yourself or return frequently to your provider. Weight regain usually occurs after stopping tirzepatide. Maintaining lifestyle changes, like regular physical activity and a healthy diet with reasonable portions, can help keep the pounds off.

Question 1

What is tirzepatide? How does it work for weight loss?

Accepted Answer

Tirzepatide is a prescription medication used for weight loss and to treat Type 2 diabetes in adults.

A weekly injection, tirzepatide acts as a dual agonist, meaning it mimics two gut peptides: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). It binds to your body’s receptors like natural hormones, increasing insulin and and reducing glucagon, a hormone that controls the amount of glucose made by the liver.

Clinical trials show these effects can help control blood sugar levels and reduce appetite, which leads to weight loss.

There are currently two FDA-approved branded forms of tirzepatide made by Eli Lilly and Company:

Zepbound is approved for weight loss for adults with obesity or who are overweight and have at least one weight-related condition, such as high blood pressure, Type 2 diabetes mellitus, or high cholesterol.
Mounjaro helps lower blood sugar for adults with Type 2 diabetes but also delivers weight-loss benefits—a plus if you’re one of the 90% of people with diabetes who are also overweight or obese.

The active ingredients in these drugs are identical, but dosing recommendations vary slightly.

Weight loss with tirzepatide can be significant.

In clinical trials, people lost 15% or more of their starting body weight with tirzepatide.
In the first weight-loss studies of the drug that became Zepbound, patients treated with tirzepatide lost an average of 52 pounds over 72 weeks, more than 20% of their starting body weight. Those taking a placebo lost just 3% of their body weight, on average.
Nearly a third of people taking the highest dose lost up to 25% of their initial body weight, or more than 58 pounds.

These kinds of results can be life-changing and life-saving, as weight management is a significant healthcare issue: ~70% of American adults are obese or overweight, and many have weight-related conditions.

According to the American Heart Association, losing even 5% to 10% of body weight has been shown to reduce the risk of cardiovascular disease, the leading cause of death in the U.S.

Question 2

Tirzepatide vs. semaglutide: what’s the difference?

Accepted Answer

The most well-known weight-loss drugs are Ozempic and Wegovy, which contain the active ingredient semaglutide. Ozempic is FDA-approved for the treatment of Type 2 diabetes, while Wegovy is approved for the treatment of obesity.

Tirzepatide differs from semaglutide because of its dual action as a GIP and GLP-1 receptor agonist. Semaglutide only mimics the incretin hormone GLP-1, while tirzepatide acts like two incretins. This dual action may be more effective for some patients, according to Dr. Brandon Richland, a board-certified plastic surgeon in Newport Beach, California. He offers a medically supervised weight-loss program that includes semaglutide or tirzepatide, depending on how the patient responds.

“Generally, we’ll start patients on semaglutide. If they plateau on it, we switch them over to tirzepatide, so they can continue to lose more weight,” Dr. Richland explains.

Question 3

Good candidates for tirzepatide

Accepted Answer

Before taking tirzepatide, it’s important for a healthcare professional to evaluate your complete medical history and current medications. For instance, birth control pills may not work as well while taking this medicine, and taking tirzepatide with other medicines to treat diabetes, such as sulfonylureas or insulin, may increase your risk of hypoglycemia (low blood sugar).

Tirzepatide is FDA-approved for chronic weight management in adults, but the manufacturer recommends that patients meet one of these criteria:

A body mass index (BMI) of at least 30
A BMI of at least 27, with one or more weight-related health conditions, such as Type 2 diabetes, sleep apnea, hypertension, or high cholesterol

A healthcare provider may still prescribe tirzepatide for weight loss even if you don’t meet these BMI criteria, but this would be considered an “off-label” use of the medication.

It’s not unusual for providers to prescribe tirzepatide to healthy people who aren’t technically overweight, but are looking for an edge to reach their ideal weight, says Dr. Richland. “I don’t think it should necessarily be seen as a fad diet or as a way to help someone drop 10 pounds and then go back to their old habits,” he says. “But if someone is going to be motivated, have a good diet, and exercise appropriately, I think this can be a good jumpstart to a healthy weight loss plan.”

Risk factors

Tirzepatide may cause thyroid C-cell tumors. Tell your provider if you have a personal or family history of thyroid cancer.
The same goes for multiple endocrine neoplasia syndrome Type 2, a rare syndrome that causes tumors to develop on endocrine glands.
“A rare but concerning side effect is pancreatitis, an inflammation of the pancreas,” says Dr. Richland. It isn’t yet known for certain whether the drug is safe for people who’ve had this condition in the past.
Tell your provider if you have or have ever had kidney disease, a history of diabetic retinopathy (damage of blood vessels in the eye), or any stomach problems, such as difficulty digesting food.
Inform your provider if you plan to become pregnant, are pregnant, or are breastfeeding. There haven’t been enough clinical trials to determine whether tirzepatide is safe during pregnancy, but it caused harm to unborn babies in animal studies. Contact your healthcare provider right away if you become pregnant while taking tirzepatide.

Some people have reported suicidal thoughts and behaviors with other long-term weight management medications. Contact your provider if you or your loved ones notice a change in your mood or behavior.

Question 4

How do you get tirzepatide for weight loss?

Accepted Answer

Tirzepatide is only available with a prescription. A licensed healthcare provider, seen in person or online via a telehealth service, must assess your health before prescribing it.

Plastic surgeons often offer tirzepatide as part of a comprehensive program for patients struggling with weight loss, including those preparing for surgical procedures.

Having a prescription filled at a traditional retail pharmacy can be very challenging, as demand so far outstrips supply for the drug and injection pens. “You walk into the pharmacy and they’re like, ‘Sorry, we won’t have any for four months,’” says Dr. Richland. If you can find it, the cost can be exorbitant if it’s not covered under your insurance—and sometimes even if it is. (More on cost later.)

Due to high costs and availability challenges, many providers offer prescriptions for compounded forms of tirzepatide. In addition to being more cost-effective, compounded drugs help prevent interruptions in treatment when commercially available medications are unavailable due to manufacturing or supply issues.

Drug compounding is a legal, widely accepted practice. People may receive a prescription for compounded medicine because they need a special formulation, to save money, or because of a drug shortage in their area.

Medications dispensed by compounding pharmacies have nearly identical active ingredients as those from a retail pharmacy. “It’s still tirzepatide, and it’s as effective, but it’s without the additives the manufacturer uses,” says Dr. Richland.

You can also buy tirzepatide online with a valid prescription. Just be sure to buy it from licensed, well-regulated sources that supply safe and legitimate medications.

Question 5

Tirzepatide pros and cons

Accepted Answer

Pros

It’s a proven method for medically assisted weight loss. “For people who are dieting and exercising and losing a little weight or none at all, this medication really kickstarts things moving in the right direction,” says Dr. Richland.
In clinical trials, tirzepatide was found to be effective and safe, with no major adverse events.
Weight-loss drugs like tirzepatide don’t outperform bariatric surgery, but they spur greater and more sustained weight loss than any prior medication.
Losing weight can have big health benefits. "Many patients are seeing improvement in blood pressure, lipid [cholesterol] levels, cardiovascular disease, and glucose levels,” says Dr. Richland.

Cons

Both brand-name and compounded forms of tirzepatide can be expensive, and health insurance may not cover it.
As with all medications, side effects can occur. The most common are gastrointestinal-related and include nausea, constipation, diarrhea, and heartburn. These mostly occur when the dose of tirzepatide is increased; slowly increasing the dose usually helps reduce them.
Other side effects include injection site reactions, hypersensitivity reactions, and fatigue.
The drugs are administered via a weekly injection. You’ll either need to get comfortable injecting it yourself or return frequently to your provider.
Weight regain usually occurs after stopping tirzepatide. Maintaining lifestyle changes, like regular physical activity and a healthy diet with reasonable portions, can help keep the pounds off.

Question 6

How much does tirzepatide cost? Does insurance cover it?

Accepted Answer

There are many variables associated with the cost of tirzepatide.

Without insurance, Mounjaro costs $1,000 to $1,200 per month, and sometimes more. Most insurance plans do cover this medication when it’s prescribed to treat Type 2 diabetes.
The list price for a 28-day supply of Zepbound is $1,060, according to GoodRx. Without insurance or manufacturer discounts, that translates to a cost of $13,800 per year. Costs vary by pharmacy, so it pays to shop around.

If your health insurance plan covers these medications, “You have to meet strict criteria, and even then, you may not get approved,” says Dr. Richland.

If your plan covers Zepbound, you may be able to get the medication for as low as $25 for a 1- or 3-month prescription through the Zepbound savings card program.
If your plan doesn’t cover Zepbound, you may still be eligible to pay $550 per prescription, about half the list price.

Prices for compounded tirzepatide average $500 a month, depending on the dosage. Insurance doesn’t always cover compounded drugs, but some doctors offer compounded tirzepatide as part of broader weight-management programs. These typically include the drug itself, a full health assessment, monitoring, coaching, dietary recommendations, and lab work. For example, Dr. Richland offers his patients a program that costs between $500 and $1,500 per month.

Medicare is not allowed by law to cover weight-loss drugs, though changes are afoot that may soon allow coverage if the drug is prescribed to reduce the risk of heart attacks and strokes. For now, this would only apply to Wegovy, which has also been FDA-approved for lowering the risk of stroke and heart attack in overweight or obese adults who do not have diabetes.

Question 7

How soon does tirzepatide start working?

Accepted Answer

“Some people feel the effects within a few days, but most patients feel the effects within a week or two,” says Dr. Richland.

You’ll know it’s working when you start feeling fuller after meals and less desire to eat. “It's increasing that feeling of satiety, so whereas before maybe you would have a whole chicken breast and some rice and vegetables, now you’d have a quarter of a chicken breast, a little bit of vegetables, and the rice doesn’t look so good,” says Dr. Richland.

Besides reducing hunger, injectable medication like tirzepatide can also help quiet “food noise,” the constant and persistent thoughts about food some people have. According to recent research, food noise can contribute to patterns of overeating and emotional eating.

Dr. Richland has also noticed that people drink less alcohol on these medications, and the research is bearing this out. In a recent study, both average drinks and the odds of binge drinking were found to be significantly lower in patients taking semaglutide or tirzepatide, compared to the control group.

Question 8

Is compounded tirzepatide safe?

Accepted Answer

Compounded tirzepatide is safe when it’s obtained with a prescription from a licensed healthcare provider and compounded in compliance with strict guidelines and regulations. The Pharmacy Compounding Accreditation Board lists accredited compounding pharmacies by state.

It’s important to remember that while the active ingredients (such as tirzepatide) are approved by the Food and Drug Administration, compounded drugs aren’t, and the FDA does not verify their safety, effectiveness, or quality.

Your prescribing provider should help ensure that you’re getting your medication from a reliable source. That was one of Dr. Richland’s goals when he started offering a medically supervised weight-loss program in his office. “We wanted to give patients more cost-effective access to these injections and let them know that they’d be getting the actual medication and not just, ‘Hey, I found something online, I hope it’s what they say it is,’” he says.

Toward that end, his staff thoroughly vet the compounding pharmacies they use, including getting a Certificate of Authenticity to make sure the product is what it’s supposed to be.

What’s definitely not safe is playing pharmacist at home to make your own weight-loss drugs. According to Everyday Health, the DIY process includes buying a freeze-dried, powdered form of tirzepatide or semaglutide online (materials that carry warning labels “for research only” or “not allowed for use in humans”) and reconstituting it with bacteriostatic water, to help prevent the growth of bacteria. This purportedly creates the equivalent of the brand-name drug.

“Instead of meth labs, people have semaglutide labs,” says Dr. Richland. Instructions for these homemade injections can be found online, but for safety’s sake, heed the FDA warning that this practice poses significant risks.

Question 9

Tirzepatide side effects

Accepted Answer

Some side effects of tirzepatide can be more noticeable than others. Here’s the lowdown on three of the most common ones.

Skin laxity

There’s no getting around the fact that pronounced weight loss in a relatively short time can take a toll on your face. Skin may appear looser or wrinkles seem more pronounced.

These unwanted facial changes are due to the loss of facial fat that helps skin stay taut and full.

“Anytime you lose weight, you’re going to end up with increased skin laxity,” says Dr. Richland. “Unfortunately, when you lose weight, you can lose it everywhere—including the face.”

Losing weight gradually can help minimize the effects. “The faster you lose weight, the less likely it is that your skin can snap back,” says Dr. Richland.

You may be losing weight too quickly if you’re experiencing what’s been dubbed “Ozempic face,” so speak to your healthcare provider. Some augmentation with fillers or fat grafting may be in order.

Hair loss

Weight loss with tirzepatide may be accompanied by hair loss (it’s noted in Zepbound’s labeling). It occurs in around 6% of people taking the highest dose of the drug, and it’s typically temporary.

Hair tends to thin versus coming out in clumps or leaving a bald spot. Usually, once your weight stabilizes, the hair will regrow to its original thickness.

Fatigue

Fatigue isn’t listed as a potential side effect of Mounjaro, but it is listed in Zepbound’s labeling. The good news is that tiredness is typically mild.

You might feel more fatigued while taking these drugs for several reasons. For example, the medication can decrease appetite, and eating fewer calories may zap your energy.

Hypoglycemia (low blood sugar) isn’t an expected side effect of either drug alone, but if combined with other medications for treating Type 2 diabetes, there is a risk for hypoglycemia, which can manifest as fatigue. If you experience this, speak to your prescribing healthcare provider.

Question 10

How is tirzepatide administered?

Accepted Answer

Tirzepatide is administered under the skin (subcutaneously) using a single-dose prefilled pen with a hidden needle. It’s available in six dosage strengths: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg.

Initially, 2.5 mg is injected once a week for 4 weeks. Dr. Richland says this initiation dose is designed to get your body used to the medication. “You have to dose in a controlled manner,” he says. “If you start off at even the second- or third-tier dose, you can experience horrible nausea and vomiting.”
After the first month, the dose is typically increased to 5 mg weekly.
The dose can be increased in 2.5-mg increments up to a maximum dose of 15 mgs, with at least 4 weeks on each dose.

This slow titration helps minimize side effects.

The injection is generally given into the abdomen, thigh, or back of the arms. These areas often have an adequate layer of fat, which facilitates the medication’s absorption.

The manufacturer says to change your injection site each week: You may use the same area of your body, but choose a different injection site to avoid pain and bruising.

When administering tirzepatide in the abdomen, choose a location roughly two inches away from the belly button.

Wherever on your body you choose to inject tirzepatide, don’t fear the needle, says Dr. Richland. “It’s a tiny little prick, and sometimes you don’t feel it at all.”

Question 11

How long can you take tirzepatide?

Accepted Answer

Tirzepatide is considered a long-term medication.

Recent research confirms that if you want to keep the weight off, you may have to stay on it, potentially for the rest of your life.

After taking Zepbound for 9 months and seeing their total body weight reduced by 21%, participants who stopped the medication for a year regained 14% of their weight.
The researchers didn’t evaluate the effects of the behavioral therapy all participants received to help them stick to a healthy 500 calories per day deficit diet and at least 150 minutes of physical activity per week.
However, this lifestyle counseling may account for why they didn’t regain all the weight after discontinuation of the drug.

“If you stop the medication, you regain the weight. There’s no question that will happen,” says Dr. Louis Aronne, lead study author and director of the Comprehensive Weight Control Center at Weill Cornell Medicine. But that shouldn’t be surprising, he says. “Obesity is a chronic condition, like diabetes or high blood pressure. So, it must be treated chronically.”

Dr. Richland notes that his patients generally regain some weight once they stop the medication, “but as long as they maintain a good diet and exercise regularly, most patients don’t return to their previous weight.”

One reason for this is that the medication seems to help break bad habits. “Patients tell us that being on the medication trained them to realize that, even though they were told their whole life to eat your whole plate or eat this many calories, they don’t need to eat that much anymore,” says Dr. Richland. “That’s been helpful for them long-term in maintaining their results, even after they stop injections.” And if their weight ever does start inching upward, they can always restart the medication.

Question 12

Sources & studies

Accepted Answer

Aronne, Louis, et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA 2024 Jan 2;331(1):38-48.

Garvey, TW, Frias JP, Jastreboff AM, le Roux C, Sattar N, Aizenberg D, et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. The Lancet. Volume 402, Issue 10402, P613-626, August 19, 2023.

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