Amy Schumer says Mounjaro® + HRT helped her lose weight with fewer side effects

Amy Schumer’s recent weight loss highlights an important truth about modern weight loss: finding the right medication isn’t always straightforward.

With so many GLP-1 options out there, it can take time—and a bit of trial and error—to find the one that fits your body and lifestyle.

The comedian has been open about trying Ozempic® and Mounjaro®, two popular GLP-1 medications, several years apart. Both are approved to treat type 2 diabetes, but can be prescribed off-label for weight loss. Ozempic’s weight-loss counterpart is Wegovy®, which also contains semaglutide, while Mounjaro’s is Zepbound®, made with tirzepatide.

On paper, these medications are similar—but as Schumer’s experience shows, one might work better for someone than another. And the side effects can be very different. 

Mounjaro® vs. Ozempic®: Two very different side effect experiences

Schumer has been candid about her contrasting experiences. She described her time on Ozempic® (semaglutide) as “horrible,” marked by severe nausea, vomiting, and fatigue that left her “bedridden” and too weak to play with her young son. She eventually stopped taking it, saying the rapid weight loss wasn’t worth the toll on her quality of life. 

In contrast, Schumer says her experience with Mounjaro® (tirzepatide) was really good. When paired with hormone therapy for perimenopause, she not only tolerated the medication better but noticed benefits beyond the scale—like increased energy, improved mood, clearer skin, and even fuller hair.

Her honesty about using multiple tools—including past cosmetic procedures—underscores an important point: sustainable weight management is personal and often multifaceted. Even medications in the same family can feel completely different depending on a person’s biology, hormone balance, and how their treatment is managed.

“Amy Schumer’s story perfectly illustrates why finding the right medicine and the right dose is so important,” says Dr. Karen Mann, MD, OB-GYN and Noom Medical Director. “Her experience also shows how pairing a GLP-1 medication with hormone therapy can be especially effective for women in their 40s and beyond, when perimenopause can make weight loss more challenging. Success with these medications takes time and depends on personalizing the care, not rushing the process.”

Amy Schumer’s very different experiences with semaglutide and tirzepatide aren’t unusual. Research shows that some people experience fewer side effects with tirzepatide, even though both medications work in similar ways to regulate appetite and blood sugar. Let’s take a closer look at how they differ—and which side effects tend to happen less often with tirzepatide.

Semaglutide vs. Tirzepatide: Which is better for weight loss?

Semaglutide and tirzepatide work in similar ways, but their subtle differences can influence how much weight someone loses and how well they tolerate treatment. Let’s take a closer look.

Weight loss with semaglutide 

Semaglutide mimics the hormone GLP-1 (glucagon-like peptide-1), which helps control appetite and blood sugar. It comes as: 

• Ozempic®: approved for type 2 diabetes
• Wegovy®: approved for weight loss and heart health

People taking the highest dose of semaglutide (Wegovy 2.4 mg) lost an average of 15% of their body weight over 68 weeks.

Weight loss with tirzepatide 

Tirzepatide acts on two hormones—GLP-1 and GIP (glucose-dependent insulinotropic polypeptide)—for a dual effect on appetite and metabolism. It comes as: 

• Mounjaro®: approved for type 2 diabetes
• Zepbound®: approved for weight loss and obstructive sleep apnea (OSA)

People taking the highest dose of tirzepatide (15 mg) lost an average of 21% of their body weight over about two years.

Real-life weight loss results can vary

So, what does that mean in real life?

On average, research suggests tirzepatide may lead to greater weight loss than semaglutide—but remember, those numbers reflect averages from clinical trials, not guarantees. Your individual response can depend on factors like genetics, hormone balance, and how gradually your dose is increased. Even small details, like how you eat or move while taking the medication, can influence both results and side effects. 

Some people even find success with lower doses—what’s often called GLP-1 microdosing—especially when paired with nutrition and lifestyle changes that fit their body.

All of this underscores one essential truth: the best medication is the one that works for you. Personalized medical guidance and a flexible mindset are key to finding what truly supports your goals.

Your eating and movement habits play a big role in your results, too. That’s why finding what truly works for you takes both expert guidance and an open mind.

Mounjaro® vs. Ozempic®: Which has fewer side effects?

Both tirzepatide and semaglutide medications can cause similar side effects, but how people experience them can vary quite a bit. Studies show that semaglutide may trigger slightly higher rates of certain digestive symptoms at the highest doses.

Here’s what the research shows:

• Nausea is the most common side effect for both medications, affecting about 44% of people.
• Diarrhea occurs at nearly the same rate: 23% for semaglutide and 24% for tirzepatide.
• Vomiting happens more often with semaglutide (21%) than with tirzepatide (15%).
• Constipation is also slightly more frequent with semaglutide (29%) compared to tirzepatide (27%).
• GERD (acid reflux) affects 11% of semaglutide users versus 6% with tirzepatide.

The overall side-effect profiles are very similar, but small differences can make a big impact on how someone feels day to day. That’s why two people can take medications in the same class and have totally different experiences.

For many, the side effects are typically mild and temporary, and people adjust as their body adapts to the medication. But for others, certain symptoms—like nausea or fatigue—can be more difficult to manage and may require changing the dose or even switching medications.

How Schumer’s experience reflects the research

Amy Schumer’s story lines up closely with what studies have shown. She found semaglutide’s side effects so intense that she had to stop taking it, while her experience with tirzepatide felt far more manageable.

In interviews, Schumer has shared that she carries a gene that predisposes her to nausea—a factor that could explain her strong reaction to semaglutide. It’s a reminder that biology plays a big role in how each person responds to medication. What feels tolerable for one person can feel impossible for another.

It’s also worth noting that Schumer’s improved experience with tirzepatide might have been influenced by her use of hormone therapy for perimenopause. Hormone replacement therapy (HRT) can help stabilize symptoms like sleep disruption, anxiety, and mood swings—changes that might otherwise intensify medication side effects.

Taken together, her story shows why personalized care matters so much. The right medication, the right dose, and the right support system can completely change how well a treatment works—and how good you feel along the way.

The bottom line: Find the right medication for you

Amy Schumer’s story is more than a celebrity weight-loss tale—it’s a reminder that the “right” medication looks different for everyone. Her rough experience with semaglutide and smoother results with tirzepatide show how even medications in the same class can feel completely different in your body.

In Schumer’s case, pairing a GLP-1 medication with hormone therapy may have helped ease perimenopausal symptoms while improving energy, mood, and weight management. But her openness also reflects a bigger truth: lasting weight care rarely depends on one solution.

It’s about combining the right tools—medication, nutrition, movement, and mindset—under the guidance of a team that helps you personalize every step.

If you want to explore GLP-1 medication, see if you qualify for Noom Med. You’ll be connected with a clinician who can find the right medication for you, prescribe it if needed, and personalize your care. They help you navigate side effects, develop an eating and exercise plan that minimizes them, and adjust your dosage safely. They can even change your medication if one works better for you. 

Because at the end of the day, the most effective plan isn’t the fastest one—it’s the one that fits you.

 Ozempic^® and Mounjaro^® are not FDA-approved to treat obesity or for weight loss.