It’s easy to be cynical about the pharmaceutical industry. Drug prices are outrageous. Pharmacy benefit managers add opacity and cost. And everywhere you look, someone is pushing a supplement or a “natural” alternative as a better path.
But every so often, I take a step back and marvel at what modern drug development is actually accomplishing.
We're in a golden era of biomedical innovation.
And in this newsletter, I want to quickly highlight a few developments that I think are genuinely astounding.
🧬 Oral PCSK9 Inhibitors Are (Probably) Coming
I’ve written before about PCSK9 inhibitors, which are a class of cholesterol-lowering drugs that I called “the coolest medical story that you probably haven’t heard about.”
These drugs were modeled on people with a rare genetic mutation: a loss-of-function in the PCSK9 gene. These individuals had incredibly low LDL cholesterol and almost no heart disease - and drug companies turned that genetic variation into medicine.
From genetic outlier to proven therapy in under a decade.
But so far, PCSK9 inhibitors have one barrier to wider adoption: they’re injectables. Even patients who are willing to take them sometimes can’t get them covered.
That may change. A new oral PCSK9 inhibitor — AZD0780 — showed dose-dependent LDL reduction with a tolerable safety profile in the Phase 2 PURSUIT trial.
If the data holds in phase 3 trials, we might soon have a pill that mimics a powerful genetic mutation to reduce heart disease risk. That’s remarkable.
⚖️ Obesity Might Be Solvable in Our Lifetime
When I was in training, watching the CDC’s obesity maps year by year was incredibly disheartening. The trends just kept worsening.
But the GLP-11 revolution - with drugs like Ozempic, Wegovy, Mounjaro, and Zepbound2 - has completely changed the game.
And the pipeline isn’t slowing down.
I’m not exaggerating when I say that there’s a fair chance that obesity is going to be solved in our lifetimes
🇨🇳 Mazdutide: A New Player from China
A Chinese biotech company, Innovent, recently published data on Mazdutide, a dual GLP-1 and glucagon receptor agonist. It produced weight loss comparable to Ozempic — about 15% of body weight.
New players mean more options, better prices, and broader access.
That’s important, because:
Some people don’t respond to one drug but do to another.
Side effects can vary significantly between agents.
Competition usually means more affordable medications and greater availability for patients
🧪 Retatrutide: The Triple Threat
Retatrutide, still in the pipeline, might outperform all of them. It targets GLP-1, GIP, and glucagon receptors — and in early studies, caused weight loss of around 17% of body weight.
That’s 34 pounds lost for someone starting at 200 lbs, or 51 pounds at 300.
It’s also well tolerated and based on a familiar principle in medicine: combination therapy across multiple biologic pathways often leads to better outcomes — as we've seen in heart failure, HIV, and TB.
🆚 Tirzepatide Beats Semaglutide (SURMOUNT-5)
We finally have a head-to-head trial comparing tirzepatide (Zepbound) and semaglutide (Ozempic) at the right doses.3
And tirzepatide wins.
This tracks with what I’ve been telling patients and what placebo-controlled trials have hinted at for years.
If you have the choice, Zepbound likely edges out Ozempic.
But both are outstanding options.
💊 The Ozempic Pill: Useful, But Less Potent
Injectables are a major barrier for some patients. That’s where oral semaglutide (brand name: Rybelsus) comes in.
My anecdotal experience: it’s well tolerated but less effective.
Now we have data to confirm that: the SOUL trial showed a modest reduction in cardiovascular events in diabetics — from 14% in the placebo group to 12% in the treatment group.
That makes sense. The oral form causes less weight loss, so it likely yields less benefit on heart disease and metabolic outcomes.
But it’s still a real option for those unwilling or unable to inject.
🔥 A New Therapy in Giant Cell Arteritis
Let’s pivot quickly to a very different condition: giant cell arteritis (GCA), a large-vessel vasculitis that often leads to prolonged high-dose prednisone use, with all the usual side effects (weight gain, osteoporosis, glucose issues, and more).
The SELECT-GCA trial just showed benefit for Upadacitinib, a JAK inhibitor, in reducing the need for long-term steroids.
I’m not a rheumatologist, but I’ve had a few patients really suffering with GCA and seen up close how miserable this condition can be.4
Plus any alternative to months of prednisone is almost always a huge win.
🧠 Final Thoughts: Innovation Deserves Its Due
It’s easy to criticize the pharmaceutical industry.
And let’s be clear, drug prices in the U.S. are almost indefensible.
But those costs aren’t for nothing. We pay more for two very clear reasons:
We subsidize R&D for the rest of the world.
The U.S. drug supply chain is riddled with rent-seeking middlemen (hi, PBMs).
Of course, Big Pharma is profit-driven. But at least they’re creating something of value.
The naturalistic fallacy is seductive, but misleading.
Real people face real medical problems. And real drugs - even in our flawed system -often provide the best hope for relief.
I still believe food is medicine and that exercise is the most powerful intervention I can recommend.
But I also believe that pharmaceuticals, when used wisely, are one of the most meaningful tools we have to help people live better and longer lives.
We’re living in an era where that’s more true than ever.
It’s more accurate to call this class of drugs “incretin mimetics,” but Ozempic is a GLP-1 agonist and it’s really the one that came first.
Zepbound is the same as Mounjaro and Wegovy is the same as Ozempic.
One of the most interesting examples of not using the right dose of a drug in a comparison like this comes from the COMET trial in cardiology, where carvedilol was better than poorly dosed metoprolol. A study done with an inferior comparison leaves lack of clarity about the true answer. That wasn’t the case in SURMOUNT-5.
And if you’re curious, go on the Reddit threads, Facebook groups, or GCA patient advocacy groups to see how difficult this can be for patients.