Are All Weight Loss Drugs Created Equal?
When it comes to modern medicine, we usually assume that progress and precision are bedfellows. Million-dollar machines focus gamma rays on tumors the size of a dime. Elegant prosthetic legs react to whispers of electricity from sub-millimeter wisps of nerve. Oncologists can update your immune system with custom-designed cancer-fighting proteins.
Smaller and smarter. Wherever you look, that’s the trend. Everything is more niche, more specialized, more personalized. Spotify curates our music and Stitchfix tailors our wardrobe. The artisans at Goyard obligingly adorn our handbags with custom monograms. If it wasn’t made just for us, it doesn’t deserve to be associated with us.
So, when it comes to weight loss and the GLP-1 cartridges nestling in the bok choy at the bottom of our refrigerators, we should choose the option with the most precise molecular profile. We want a medicine that works like a heat-seeking missile, homing in on that one infuriating protein that makes us reach for the Cheez-Its, that’s the id to our dietary superego. We want a medicine that’ll wrestle that one target into mute submission, so the rest of our body can go along its merry way.
Right?
Well, maybe not. In fact, we’ll go a step further: Probably not.
Precision isn’t always a clinical virtue. In the 1940s, French chemists were hunting for antihistamines to calm patients before surgery. The chemists stumbled on a molecule called chlorpromazine. As an antihistamine, it was pretty mediocre. But as a sedative for surgical patients, it was magic.
Why was chlorpromazine such a massive success? Because it was marvelously imprecise. It did much more than just block histamine receptors. It threw an arm bar across half the psychoactive transmitters known to mid-Twentieth Century science. It modulated adrenaline and dopamine and serotonin, along with histamine.
Instead of pulling one lever, chlorpromazine pulled a half-dozen. Modern psychopharmacology was off to the races.
Let’s extend the frame to the two leading weight loss medicines—Ozempic and Zepbound. Ozempic targets GLP-1, a protein that blunts our craving for food and unlocks internal stores of insulin.
Like Ozempic, Zepbound speaks to our brain, pancreas and gut through GLP-1. But it also links up with GIP, a receptor that lines the early stretches of the small intestine. When Zepbound links up with GIP, our brains get a second signal telling us that our bellies are full—that it’s not just acceptable but preferable to step away from the Cheez-Its. Zepbound also does double duty in the pancreas, using GIP as a backup signal to keep blood sugar under control.
Ozempic pulls one molecular lever. Zepbound pulls two. Which means, on paper, that Zepbound should do a better job of keeping weight and blood sugar in check.
But, as any pharma CEO will remind you when justifying drug prices, “on paper” and “in the real world” are two very different things.
Does the latest research on GLP-1s support Zepbound’s messier, imprecise approach? In a word: Yes.
In clinical trials, people taking Zepbound lost 40% more weight than they did on Ozempic.[1] Zepbound’s impact on weight is so profound that it also moved the needle for patients with sleep apnea. After a year on Zepbound, they weighed less and slept better. Their bodies were less wired with nighttime surges of cortisol and adrenaline. Their blood pressure had dropped, and they spent less time living with substandard oxygen levels.
Those are the kind of clinical outcomes that make life longer, not just better.
So, when it comes to biology and molecules, imprecision is often a virtue. But personalization still matters. GLP-1 drugs are paradigm shifters, but they’re still in their clinical infancy. Zepbound’s imprecision helps people lose weight. But it might raise the risk of side effects. Ozepmic may be a better choice for people with heart disease or osteoporosis.
That’s where Highbridge’s concierge model comes to the rescue. Standard primary care practices give their doctors 15 minutes of face-to-face time with patients, at best. That’s barely enough time to make a personalized decision about dinner, let alone a medicine you might be taking for months or years to come. You need a doctor with time and bandwidth to help you choose the medicine that will do the best job of setting your body up for longevity and health.
At Higbridge, we’re up for it. Our membership model gives you time to put your weight loss goals and fears on the table. Our direct-to-doctor phone line gives you the confidence to ask the questions you remembered right after the appointment ended. No phone trees, no wasted time, no anxious guilt about “bothering” the doctor.
And, of course, the food you put into your Zepbound-tamed stomach still matters. Highbridge can help with that, too. When it comes to untangling that messy nexus of food and physiology and culture, few people are better than Abby Greenspun at Abby Greenspun Nutrition. Abby understands that food is more than just molecular gasoline. It’s also a vehicle for emotion, a ritual that can bring together past and present, family and history.
[1] While the biostats mob runs for torches and pitchforks, here’s how I come up with the 40% figure. Patients on Zepbound lost, on average, 21% of body weight. (Jastreboff et al. NEJM 2022.) Patients on Ozempic lost 15% (Rubino et al. JAMA 2022. Wilding et al. NEJM 2021) 21% - 15% = 6%. And 6%/15% = 0.4.
