Episode 142: Tirzepatide II - a podcast by Rio Bravo Family Medicine Residency Program

Episode 142: Tirzepatide II

Future Dr. Beuca explains that tirzepatide has shown benefits in patients with obesity that go beyond its weight-reducing effects and includes reduction of blood pressure, among others. Dr. Arreaza explains that Wegovy (semaglutide approved for weight loss) is also very beneficial for weight loss and explains.  

Written by Maria Beuca, MSIV, Ross University School of Medicine. Comments by Hector Arreaza, MD.

You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.

Maria: Hello everyone, today is June 2, 2023, and we want to re-visit our discussion about the drug Tirzepatide from our May 19th, 2022. 

A little re-cap for those of you who don’t know, tirzepatide, also known by the brand name Mounjaro, is a drug that was approved by the FDA a year ago for the treatment of type 2 Diabetes. It is similar to the drug Semaglutide, also known by the brand name Ozempic which many of you may be more familiar with, thanks to the Kardashians and other celebrities making it popular as a “weight loss” drug. 

Arreaza: The brand name for weight semaglutide is Wegovy.

Maria: Both of these drugs are injected once a week and mimic the effect of the incretin hormone GLP-1 by binding to its receptor. Incretin hormones are a group of hormones that cause insulin to be released from the pancreas after eating to help lower blood sugar levels.  These incretin hormones also help suppress the appetite, causing you to eat less and lose weight. Tirzepatide is different because it is the first drug to mimic the action of two hormones, both GLP-1 and GIP. 

In our last episode, we also discussed the SURPASS-2 study that showed tirzepatide to be superior to semaglutide because of this dual incretin action, with greater weight loss, lower HA1c levels, and lower triglyceride and VLDL levels. At that time, we also mentioned the SURMOUNT-1 Phase 3 clinical trial that was ongoing at the time. Well, it is now complete, and the results are in. There were 2,539 obese or overweight participants without diabetes in the study who lost between 16-22.5% of their starting weight on Tirzepatide. On 15 mg dose, participants lost about 52 lbs (24 kg), on 10 mg 49 lbs (22 kg) and on 5 mg about 35 lbs (16 kg), but those on the placebo lost only 2.4% or about 5 lbs (2 kg). As you can see there is very little difference in weight loss between the 10 mg dose and the 15 mg dose, although a big difference is seen compared to the 5 mg dose. It’s important to note that they took Tirzepatide for 72 weeks or a year and a half. 

Arreaza: That’s very significant weight loss. It is important to emphasize that these patients did NOT have diabetes. 

Maria: These weight loss results have proven to be comparable to bariatric surgery. The study also showed improvement in cardiovascular and metabolic risk factors such as lower blood pressure, fasting insulin, lipid levels and even aspartate aminotransferase levels in comparison to the placebo. By the end of the study, more than 95% of the participants who had pre-diabetes had converted to normal glucose levels. This study was so impressive that it was presented at the 82nd Scientific Sessions of the American Diabetes Association and was also published in The New England Journal of Medicine. 

Arreaza: It seems like tirzepatide is ahead of the game for weight loss.

Maria: Although it is approved as a drug for diabetes, the next step is to approve it for weight loss and to begin treating obesity as a chronic disease that needs to be treated. 

Maria: And this makes sense. Currently, more than 4 in 10 American adults have obesity, and obesity is the cause of many other conditions. Just yesterday, I was seeing patients in the orthopedic clinic and I had several patients being seen for knee pain due to obesity, and they are postponing surgery because they have been losing weight on tirzepatide and are already feeling better. I think avoiding knee surgery alone is a pretty good reason to approve these drugs for weight loss, but there are many other conditions that are improved by weight loss. 

Arreaza: My anecdotes are related to semaglutide, but I can imagine that this may also apply to tirzepatide. I had a patient who was able to stop all antihypertensive medications because of 40-lb weight loss. 

Maria: Dr. Caroline Apovian, director of the Center for Weight Management and Wellness at Brigham Women’s Hospital, states that “If everybody who had obesity in this country lost 20% of their body weight, we would be taking patients off all these medications for reflux, for diabetes, for hypertension. We would not be sending patients for stent replacement.”

Maria: Last month, officials from Eli Lilly, the company that makes tirzepatide, stated that they are hoping to have a fast-track approval to sell it for chronic weight management by sometime this year. 

The problem is that many of these patients who were prescribed Tirzepatide have not been able to get it because it has been out of stock for the last few months in all the local pharmacies. They get the prescription, start taking Tirzepatide and begin to lose weight or improve their blood sugar levels and then it is out of stock and now you have people with Diabetes who have gotten off insulin because Tirzepatide worked so well and suddenly they can’t get it and are at risk for getting pretty sick without it. 

Arreaza: The manufacturer of Wegovy announced this, “we will only be able to supply limited quantities of 0.25 mg, 0.5 mg, and 1 mg dose strengths to wholesalers for distribution to retail pharmacies which will not meet anticipated patient demand. We anticipate that many patients will have difficulty filling Wegovy® prescriptions at these doses through September 2023. We do not currently anticipate supply interruptions of the 1.7 mg and 2.4 mg dose strengths of Wegovy®”. Why is this happening? 

Maria: The problem is that this drug was not meant for the masses, for all these young girls wanting to lose a few pounds for aesthetic reasons. It was meant for people with a BMI 30 or with a BMI 27 plus another comorbidity such as hypertension. Celebrities have brought attention to these drugs for weight loss, for example Ozempic has over 433 million views on TikTok. It has gotten so bad that people are turning to questionable sources online to purchase these drugs, where it is given cute names like “skinny shots.” 

And if your insurance does not cover Tirzepatide, it is still expensive, starting at around $1000 per month. Some of the insurers who used to cover the cost stopped covering it or placed new restrictions on who qualifies. 

Another downside is that tirzepatide and other drugs of this class have not been on the market that long, so the long-term effects are still not known. So far, early evidence shows that most people gain the weight back as soon as they stop taking it, so are the weight loss benefits sustainable at this high cost? 

Maria: We talked about the adverse effects in the last episode, but it’s important to go over them again. Patients can have diarrhea, nausea, vomiting, constipation, and abdominal pain that can often bring these patients into the clinic or even the Emergency room thinking they are ill, when in fact it is an adverse effect of their medication, especially the first few days of starting or increasing the dose. So, educating patients is very important before they start this new drug. There is also a small risk of pancreatitis or gallbladder problems, so it is important to have blood work done to check the pancreas and gallbladder prior to starting tirzepatide. There is also a warning to avoid using it if you have a family or personal history of thyroid cancer. 

Arreaza: Reminder, MEN type 1. I would like to mention the so-called “Ozempic face”. It is the face you get with rapid weight loss, making you look a little older due to fat loss on the face. 

As a summary, tirzepatide is a very effective medication for weight loss, pending FDA approval. It is not free of side effects, so we still need to follow the recommendations from FDA and other reputable sources to prescribe it responsibly. There is room for further research on these medications. Currently, there are no clear guidelines regarding labs before starting treatment (lipase?) or labs for monitoring after treatment. The evidence regarding these medications continues to evolve and we should stay up to date with the changes. 

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Conclusion: Now we conclude episode number 142 “Tirzepatide II.” Future Dr. Beuca came back almost one year later to shed more light on the use of tirzepatide in the treatment of obesity. Dr. Arreaza provided some insight into the management of side effects and the potential harm of this novel medication. Overall, tirzepatide is effective and safe and may be the answer to many of our patients with diabetes and obesity. 

This week we thank Hector Arreaza and Maria Beuca. Audio editing by Adrianne Silva.

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. See you next week! 

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References:

1. Brownie, Grace. “The Problematic Arrival of Anti-Obesity Drugs.” Wired, 25 January 2023. https://www.wired.com/story/anti-obesity-drugs/
2. Dockrill, Peter. “Experimental Drug Breaks Record for Weight Loss in Latest Clinical Trial Results.”ScienceAlert, 9 May 2022, https://www.sciencealert.com/experimental-drug-breaks-record-for-weight-loss-in-latest-clinical-trial-results.
3. Frías, Juan P., et al. “Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes.”New England Journal of Medicine, 5 August 2021, https://www.nejm.org/doi/full/10.1056/NEJMoa2107519.
4. Jastreboff, Ania  M., et al. “Tirzepatide Once Weekly for the Treatment of Obesity.” New England Journal of Medicine, 21 July 2022, www.nejm.org/doi/full/10.1056/NEJMoa2206038.
5. “Label as Approved by FDA. - Pi.lilly.com.”Mounjaro Prescribing Information, Lilly USA, LLC, May 2022, https://pi.lilly.com/us/mounjaro-uspi.pdf.
6. Mounjaro. Prescribing Information. Lilly USA, LLC.  May 2022. https://pi.lilly.com/us/mounjaro-uspi.pdf?s=pi
7. “Surmount-1 Study Finds Individuals with Obesity Lost up to 22.5% of their Body Weight when Taking Tirzepatide.” 4 June 2022. https://diabetes.org/newsroom/press-releases/2022/surmount-1-study-finds-individuals-%20with-obesity-lost-up-to-22.5-percent-body-weight-taking-tirzepatide.
8. Royalty-free music used for this episode: "Happy-Go-Lucky." Downloaded on October 13, 2022, from https://www.videvo.net/ 

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