Why Orforglipron Might Become Lilly’s Top Selling Medicine

Yesterday, the cofounders of Stripe published a podcast with the CEO of Eli Lilly, Dave Ricks. It’s over 2 hours in length and a great listen for a number of reasons, but one part of the interview really stood out to me as a key piece of information regarding the future of Eli Lilly’s GLP-1 RA strategy. Here’s the podcast if you’d like to listen to it:

Over the last few years, Lilly has seen a surge in revenue from tirzepatide sales (Mounjaro and Zepbound). Just last week, they announced 3Q 2025 sales of Mounjaro at $6.5 billion and Zepbound at $3.6 billion – that’s just over $10 billion combined. Lilly’s total revenues for the period were $17.6 billion, so tirzepatide products currently account for 57% of their total revenue – in Q3 2024, it was 38%.

Investors should understandably be pleased with these numbers: they represent a fantastic ROI on the billions Lilly has invested in incretin research over the last few decades. Now as good as tirzepatide is, retatrutide looks better: fewer side-effect issues and stronger weight loss. Demand for retatrutide is incredibly high already, but Lilly might struggle to meet supply requirements once it comes to market. Dave Ricks talks about the issue with subcutaneous peptide synthesis starting 1 hour, 35 minutes into the video.

Dave mentions the capacity constraint Lilly is facing with injectable systems: they’ve made billions of doses of tirzepatide already, and he’s unconvinced that they have much room for improvements to efficiency. As a general rule, economies of scale allow large companies to produce some products at a very low marginal cost – they get better at scaling their operations and the input costs fall over time. Lilly’s CEO feels that going forward, oral solutions will be a key strategy they employ to bring the cost of GLP-1 RAs way down. As discussed in a previous blog post, orforglipron is about as good as subcutaneous semaglutide, but with a higher incidence rate of side effects.

Lilly’s previous statements seem to emphasize their capacity constraints on retatrutide to some degree. In an earnings call from October, Daniel Skovronsky said:

Moving to retatrutide, our GIP GLP-1 glucagon triple agonist. We expect results from up to six phase three studies by the end of 2026 to support the obesity and related complications program called TRIUMPH and the type two diabetes program called TRANSCEND. with its first-of-a-kind triple-acting mechanism. We expect retatrutide can deliver deeper and more rapid weight loss than existing obesity medicines, even more than tirzepatide. Of course, not all patients may need this potentially very high level of efficacy. And we believe retatrutide will likely be best suited for patients with a very high BMI or with obesity-related complications that require a high degree of weight loss. While the global development program for retatrutide includes people with a broad range of BMIs spanning across overweight and obesity, we anticipate we’ll be focused on the clinical profile of this medicine in patients where the clinical needs are the highest.

This aligns with what Dave Ricks says in the video above: retatrutide is a fantastic medicine, but it seems they’re not so keen on making it as readily available as other GLP-1 RAs. The plan seems to be to recommend subcutaneous injections to those with very high BMIs and as their body fat percentages normalize, switch them over to orforglipron. We have no idea how much orforglipron will cost, but given recent reductions in prices in many countries for semaglutide and tirzepatide medicines, it might become low enough to be a cost-saving intervention. Food spending varies from person to person and country to country, but it’s not unreasonable to suggest that using a GLP-1 RA can save you $50-$100 per week on food, which seems like a fair price point for a maintenance dose of orforglipron.

Investors might have initially thought that retatrutide would be Eli Lilly’s blockbuster sales engine for the next decade or so – but if they can scale orforglipron production quickly enough and price it aggressively, it’s plausible that by 2030, their sales from oral GLP-1 RAs will match their subcutaneous market.