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Mounjaro is the Biggest Loser

Do you remember that show The Biggest Loser? The producers of this show recruited 12 morbidly obese individuals to a compound in California, placed them on rigid calorie restriction, forced them to exercise 8 hours per day, and had them compete to see who could lose the most weight. It was unbelievably brutal for the participants. I found the physician visits quite interesting. At the beginning of the season a physician specialized in preventative health would estimate the participant's life expectancy based on their current condition. Most of them were expected to die within the next decade. There were a lot of tears.

The results of the show were remarkable. The participants would lose up to 20 pounds in a week. One participant lost 264 lbs. in one season. That’s not a typo. The compound worked wonders. The old fashion formula of calorie restriction and intense exercise burned a ton of fat. Unfortunately, many of the participants weight returned once released back to reality.

Well, it turns out there’s an easier way. The wonderful scientists at the Ely Lilly have given us Mounjaro (tirzepatide). Mounjaro is a glucose-dependent insulinotrophic polypetide or GIP-analog. Mounjaro is also a weak glucagon-like peptide-1 agonist, which is the target of medicines like dulaglutide (Trulicity) and semaglutide (Ozempic). If it sounds like a medication for diabetes, that’s because it is, but it has several other unique properties.

GIP analogs are known to increase hormones call incretins. Incretins slow stomach emptying when someone is eating inducing early satiety. A typically person has a small amount of incretin released as they consume a meal. GIP’s put this into hyperdrive. So, individuals feel full quickly, and start feeling pain and nausea if they continue to eat.

GIPs also stimulate glucagon secretion. Glucagon takes stored glucose (glycogen) in the liver and other tissues and breaks it up into individual glucose molecules to be released into the blood stream. When glucagon runs out of glycogen it starts converting fat into sugar by process known as gluconeogenesis. Not only do you eat less, but you’re burning more as well.

You may be thinking…this is too good to be true. Does something like this exist? The answer is Yes!

Eli Lilly has been conducting clinical trials for Mounjaro for a couple of years now. Its performance as a diabetes medicine is fine. Nothing spectacular. However, its performance as a weight loss medication is outstanding. In late, 2021 Ely Lilly published the SURPASS-2 trial. A head-to-head trial against semaglutide (Ozempic; Wegovy) and clearly outperformed. (Full disclosure I’m a Novo Nordisk and Eli Lilly Shareholder, not gifts, owned personally.)

The SURPASS-2 trial was a randomized, double blind, multi-dose, head-to-head trial in patients with type 2 diabetes. Patients were randomly assigned to 5 mg, 10 mg, 15 mg of Moujaro or 1 mg of semaglutide in a 1:1:1:1 ratio. The primary endpoint was reduction in A1c. Secondary endpoints were total weight loss and percent body mass reduction. A total of 1870 patient were recruited and assigned. Each group had roughly 470 patients. The trial lasted for 40 weeks.

Patients lost on average -7.6 kg, -9.3 kg, and -11.2 kg on the 5 mg, 10 mg, and 15 mg Mounjaro doses respectively. This handedly outperformed semaglutide which only achieved a 5.7 kg weight loss. A body mass reduction of greater than 15% was experienced in 36% of participants in the 15 mg dose compared to 8% with semaglutide.

Prior to publishing SURPASS-2 Eli Lilly published a randomized controlled trial comparing Mounjaro to placebo with similar results. It’s clear that this is going to be an effective medicine to induce weight loss for obese individuals.

Demand for Mounjaro has skyrocketed. Other than Ozempic, which it bested head to head, and gastric bypass (which most patients try to avoid) there is little to stand in its way. Humira is the king of the pharmaceuticals with 200 billion in revenue over the course of its patent protection. I don’t know if Mounjaro will reach that level, but it has a chance. Patients message me daily about it. Not just obese patients. Patients with what I would consider to be normal weight. Willing to pay cash.

Graph copied from NEJM publication

The question remains, will we be better off for it. Credit is due to the pharmaceutical industry. These scientists continue to find solutions to the diseases of an advanced society. Even the one’s we can avoid. My prediction is patients from well-developed countries will pour billions into Mounjaro. One thing I can’t predict is if we will be better off for it?

I have a lot of empathy for individuals struggling with weight. The gain is insidious. It happens over many months. One day you look in the mirror and ask yourself, “How did this happen?.”

Looking back, it’s not hard to imagine myself 100 lbs heavier and thinking what it would take to lose that weight. I’ve been jogging regularly since I was in my late 20’s (I’m 40 now!). I’ve had an app on my phone MapMyRun since 2011 that records my runs. I’ve logged 2,200 miles and burned 295,000 calories over 270 hours of running. That’s about 82 lbs. If I knew that’s what it would take to lose the weight, I’m not sure I could do it. It’s a steep climb. A mountain Mounjaro can take you to the top of in 40 weeks. If you can tolerate it.

The demand for Mounjaro is evidence that we are terribly unhappy with extra weight, despite the ubiquitous “you are perfect the way you are” mantra. Although this has provided some temporary pacification it clearly doesn’t alleviate the pain many are dealing with. I’ve been prescribing Ozempic for weight loss for well over a year with success. I’ve also had patients undergo bariatric surgery with success. And I’ve had patients lose weight the old fashion way; through pain and sweat.

There is a stark contrast between these groups. Patients that have lost 40-50 lbs on Ozempic seem unphased by it. Almost annoyed. Some ask how long they need to take the medication? If they’ll gain the weight back?

The one’s that chose pain and sweat are elated. Sometimes they’re so happy they’re in tears. They make statements like, “I feel so great!” “I’m never going back.”

This is no surprise. No one claims to have climbed a mountain if they were placed on the summit by a helicopter. Joy doesn’t come from standing on the summit.

A couple of years ago Miley Cyrus had a song in heavy rotation on the radio. It was called “The Climb.” I can’t believe I’m saying this, but there was a lot of wisdom in those lyrics. I recommend listening to it occasionally. The TLDR: the joy is in the climb.

I plan to continue to prescribe Ozempic and Mounjaro to those in need because I don’t want to see people suffer, and I have some power to alleviate said suffering. However, if we as society continue to turn to the pharmaceutical industry to solve these issues, it makes we wonder if we are giving up something much bigger in the long run. Our ability to climb.

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