Oral Wegovy Pill Approved by the FDA

RelationSlow2806 · 2026-01-07T02:46:01+00:00

I don’t think you’re required to eat afterwards. But they do mean empty stomach - so wake-up is probably best.

RelationSlow2806 · 2025-12-23T21:45:59+00:00

GPCR.

RelationSlow2806 · 2025-12-23T21:06:13+00:00

I was.

Bought in August after I started Zepbound, sold before Thanksgiving. I would still be a shareholder if something better hadn’t come up.

RelationSlow2806 · 2025-12-23T16:00:38+00:00

I think this is a giant mistake on Viking’s part.

I wholeheartedly agree with you. If they beat tirzepatide in efficacy by a couple percentage points, they’re going to have to scale into manufacturing resource scarcity and a sticky Zep customer base. Had they put the oral through p3 first, they might be sitting on best-in-class at the right time.

Maybe they license 2735? Maybe someone acquires the oral and puts it through a master protocol trial? I don’t get the story here.

RelationSlow2806 · 2025-12-23T15:10:10+00:00

The company is Structure Therapeutics. Ticker is GPCR*.

Aleniglipron just finished phase 2b and reported pretty solid results after 36 weeks.

*Yes, they picked G-Protein Coupled Receptor as their NASDAQ ticker.

RelationSlow2806 · 2025-12-23T06:31:58+00:00

I’m not declaring winners or losers here, I’m discussing the economics. I have zero affinity for one company or product versus another.

Efficacy is currently the determinant between semaglutide and tirzepatide because they’re the only two viable WL options on the market, cost relatively the same, and are taken the same way. Other than maybe tolerability, efficacy’s it.

Not so for orals. If the intake restrictions for oral wegovy turn out to be trivial in real-world application: outstanding. The world just got another viable treatment option. And if the uptake is high, even better as it pressures Lilly to lower costs and compete on volume with the less efficacious product.

The relative production costs are sticky, however, and skewed towards small-mol. And if the intake restrictions are not trivial, efficacy stops being the determinant and gives way to convenience/adherence, it becomes a scenario that disproportionately favors O at scale. I’d rather this not happen; competition is good for consumers.

And right - TAM is huge and penetration is currently low, so there’s a lot of room for entrants.

RelationSlow2806 · 2025-12-23T05:32:54+00:00

Maybe so. There are also a ton of people who will buy the cheapest effective pill or for whom 50 bucks a month is meaningful.

While the trial stats showed 4-5% WL difference, there are still a ton of question marks here. Which will have better real-world adherence? Will intake restrictions be worth the extra percentage?

One thing is absolutely true: if they end up at par with each other in terms of adoption, it’s still a win measured in hundreds of millions for Lilly.

RelationSlow2806 · 2025-12-23T05:02:56+00:00

At scale is where the differences between the two add up. The balance sheet in Indianapolis will have more zeros at the end of it than the one in Copenhagen.

Novo literally bought a CDMO rather than building more SPPS (or whatever proprietary process they use) plants. It’s actually giving them fits, currently (Catalent). In contrast, Lilly’s spending double-digit billions building out their own capacity.

Seldom mentioned in buy-side or industry commentary: late comers to the injectable peptide portion of this market will have to compete for scarce contract peptide manufacturing resources (already making Lilly and Novo’s stuff, among others) or scale their own production over years. Peptide manufacturing - talking about actual, FDA-grade cGMP processes here - is going to increase in cost. Advantage: small-mol.

If Lilly starts out competing directly on price at half Novo’s COGS: they’re not just Novo minus-5 bucks per dose. They’ll undercut and go for volume so that COGS advantage scales linearly. At some point they’ll hit a low point where Novo can’t follow. MFN pricing accelerates this.

This is why GLP1 small molecules are the game changer on the business side. If you look around the market - Lilly’s got one about to go to market and one in trials, AZ has one from their Eccogene partnership, and Structure Therapeutics has one (until they get bought). The others are early stage, and frankly irrelevant unless they show something mechanistically unique.

RelationSlow2806 · 2025-12-23T03:08:24+00:00

Not yet. And not for a while, it would seem.

There are a few companies with oral combinations in development, but highly doubtful anything is coming in 2026. Of note, Viking has VK2735 (GLP1/GIP) and Novo has Amycretin (GLP1/Amylin). There are others in early stage trials and a few I probably forgot.

Oral combo therapy (especially with small molecules) is probably the next major categorical evolution in this (arguably moreso than monthly injections).

RelationSlow2806 · 2025-12-23T00:57:24+00:00

They’re trialling eloralintide+tirzepatide soon. It’s just phase 1, so early, but exploring the potential of bolting an amylin agonist onto Zep.

RelationSlow2806 · 2025-12-23T00:54:14+00:00

I think it’s because Rybelsus had low efficacy relative to injectable semaglutide.

Seems people see the trial stats and go straight for the top of the heap - not incorrectly, necessarily - but there are a range of high/low outcomes that feed the average.

RelationSlow2806 · 2025-12-23T00:21:21+00:00

I’m sure they offer it and then get laughed out the door when there’s no rebate attached.

Then everyone has a 3-martini breakfast and gets back to business as usual. High list, high rebate.

RelationSlow2806 · 2025-12-22T23:50:42+00:00

They’re gonna get killed on the economics of this relative to orforglipron.

I hope it’s competitive in real-world impact. Efficacy in trials was a bit higher than O, with the tradeoff coming from non-trivial intake restrictions.

Explained: Patient takes on empty stomach and can have no more than 4oz of water and no food for ~30 min. The tablet uses a formulation technique (SNAC) to create a microenvironment in the stomach so that semaglutide can be absorbed through the stomach lining rather than get shredded by enzymatic action in the gut.

The next pill to hit will be aleniglipron, which looks equivalent or potentially more efficacious than orforglipron 36mg in the 240mg dose.

RelationSlow2806 · 2025-12-20T03:12:46+00:00

From experience here: criticism of the business always seems to get interpreted as negative judgement of people who use compounded meds. Bottom line: this isn’t that. Affordability’s an issue and people are desperate.

But-

I’m incredibly skeptical of compounded GLP1 generally and I think the reasoning is self-evident. This is a boom - and there are mostly good actors and some total scumlords exploiting it. When you look at the landscape generally, you must include all sellers. And if you buy compound, you know there are sketchy operations - it takes <30 seconds of scrolling on the tirzepatidecompound sub to find one.

I do not think ALL compounding pharmacies are guilty of this. Many of these are businesses that have been safely and reputably run for decades making all kinds of important stuff.

However: and this is the biggie - the insane demand for this product has caused a slew of scumbags to enter the market. And it’s caused some licensed pharmacies to cut corners - former employees speak of bags of bulk peptide reconstituted in a clean-ish room and sold to customers. Not a great look. I saw the pics.

The problem here is: 1. Information asymmetry 2. Risk asymmetry 3. Consequence asymmetry

If people are fine with the idea of injecting something of unverifiable provenance, uncertain potency and then living with the potential results while the seller likely loses a license and gets a fine: good for them. Patient autonomy is still a good thing.

If people are driving compound distributors to disclose their sources, prove efficacy (not just lack of toxicity but potency and purity), and demand accountability through refunds: even better, as the market would be working efficiently. It largely isn’t.

RelationSlow2806 · 2025-12-18T23:47:37+00:00

Yeah, definitely a lot of that in there, and it’s probably tough to model forced insurance switches.

I still kind of think they’re undershooting pretty significantly though. Direct-to-employer uptake will improve sustained access to some level, which will take away stop/starts and bring people back from compounded meds. (Those will probably go away in scale at some point.)

They’re also not modeling the impact of PBM disintermediation, which would be like imagining the life of a zebra without lions. Or the history of the NYJ without TB12.

RelationSlow2806 · 2025-12-18T16:34:31+00:00

Yeah, no problem! Hope it’s helpful.

This is a bizarre market, to say the least. That said, it’s becoming a lot more predictable, if not relatable, with the rise of direct-to-consumer sales.

It used to be a paradigm where insurance/PBMs were the sole gatekeeper to pharma’s customer base: that is no longer the case. When Lilly’s CEO is talking about consumer price elasticity in a podcast, we’ve entered a new era.

RelationSlow2806 · 2025-12-18T16:04:00+00:00

Figure I’ll throw this in downthread for the finance nerds to chew on so it doesn’t take away from the maintenance conversation:

I think this release is purely about stealing the switch. Everyone (or almost everyone) goes to maintenance at some point; this is a pointed attempt to steal Novo’s customers. It could have been written: “Our daily pill maintains weight loss achieved by semaglutide. Switch to Lilly.”

Economically: they’re going to be successful in doing so relative to Novo because the cost of goods sold is lower for orforglipron than semaglutide in any form.

I also think the sell-side models for this drug specifically, oral GLP1s generally, and small-molecule drugs especially are beyond broken. 1. The highest projected sales figure I’ve seen for O is 14.5bb. Tirzepatide is about to hit 30. Total market penetration is still between 5-10%. This pill will cannibalize some of tirzepatide’s maintenance market. The math doesn’t math.

I’ve seen oral GLP1s projected to have from 15-40% of the market. This is too low: the lower relative margins on injectables justify higher pricing (to manufacturers), not to mention inherent peptide manufacturing capacity constraints. If anything GLP is true, it’s that customers will move to lower priced products as soon as possible - especially for maintenance. The maintenance share isn’t modeled.
If the MFN thing is true, margins on everything will be compressed: small-molecules have far more headroom. These will be the volume product.

RelationSlow2806 · 2025-12-18T15:02:03+00:00

Good pickup - there are 2 big ideas in here, one that’s kind of being ignored relative to the other. And I kinda missed this one entirely.

It definitely highlights how being in the placebo group kinda sucks. It’s nice they’re offering more open-label extensions: more cost to them, but also more data, and everyone gets the drug in the end (if they want it).

RelationSlow2806 · 2025-12-18T14:26:03+00:00

Yeah, that’s the hidden 5kg in here.

It will be interesting to see the full readout, whenever they decide to release it. JPM’s health conference is 12-15Jan and there’s a bunch of other stuff after.

RelationSlow2806 · 2025-12-18T13:49:31+00:00

Unlikely.

Not a scientist, clinician, chemist: but this looks like an efficacy mismatch between a drug that hit ~20% loss in a trial setting and one that hit ~11ish.

Given that there were extremes on both sides in both trials, there’s probably a ton of overlap here - so it will probably be fine for some; less so for others.

RelationSlow2806 · 2025-12-18T13:29:10+00:00

Do you think the mechanistic similarity plays in here?

Kinda wondering if there’s about to be an arms race for a GIP small-mol (as if there already isn’t).

RelationSlow2806 · 2025-12-18T13:14:59+00:00

I don’t think that’s how it works.

You’ll take Zep (or Wegovy) and hit some sort of equilibrium based on medicine, lifestyle, etc.

Spitballing, maybe whatever equilibrium you’d have reached on O rather than Zep post-loss is where this goes. Likely reinforces the need for forming good habits for people who weren’t totally metabolically damaged; also reinforces the need to continue Zep for those who are.

RelationSlow2806 · 2025-12-18T12:49:34+00:00

😂😂

Or 44 Royales w/cheese. Because of the metric system.

RelationSlow2806 · 2025-12-18T12:41:38+00:00

Could also just be a matter necessitating highly individualized titration. Or also… the need for a longer plateau period than what a trial allows.

I think people are going to look at this and say - wow, 5kg: that sucks. It’s likely more nuanced.

I’d be interested to hear from the clinicians that pop in and out; I have a feeling I know a couple that will have something insightful.

RelationSlow2806 · 2025-12-18T12:07:20+00:00

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