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On The Pen - Newslewtter
Jun 23
"We're knee-deep in ADA 85 coverage, but Lilly just did something they rarely do. They held a special investor event during the conference. And if you've been following the GLP-1 space closely, this wasn't about surprising us with new molecules. It was about signaling to Wall Street that Lilly is building for the long game, and laying out the clearest roadmap yet for what happens next with orforglipron, retatrutide, eloralintide, and bimagrumab.
If you missed the call, here's what actually mattered.
Orforglipron is still on track for obesity filing this year
ACHIEVE-1 confirmed what most of us already expected. Orforglipron, Lilly's once-daily oral GLP-1, delivered a 1.6%ent A1C reduction and just under 8% body weight loss over 40 weeks in people with type 2 diabetes. That puts it on par with early SURPASS numbers and sets the stage for ATTAIN-1, which will show the weight loss side in people without diabetes. Those results are expected later this quarter.
The call reaffirmed that Lilly plans to file for obesity first, with type 2 diabetes following in 2026. The delay isn't strategic, it's because the diabetes guidance requires 24 months of exposure versus 18 for obesity.
They also mentioned ongoing trials looking at orforglipron in maintenance dosing, obstructive sleep apnea, and hypertension. And they made a point to emphasize that orforglipron uses a separate manufacturing footprint, doesn't require cold chain, and won't pull supply from injectables. They're clearly positioning it as the scalable option for global reach.
GI side effects weren't out of bounds
Lilly addressed the diarrhea concerns directly. Rates were highest in India and China, lowest in Japan, and midrange in the U.S. They chalked it up to geographic and dietary differences. At the highest dose, fewer than 6 percent of patients discontinued due to GI issues. That's lower than what's been reported in many GLP-1 trials.
There were no Hy's Law cases, and liver enzymes remained stable, even among people who entered the trial with transaminase levels up to five times the upper limit of normal. Lilly wanted to be clear on this point: they are not seeing signs of hepatotoxicity.
Retatrutide is still being framed as the next tier for high-BMI patients
We didn't get new data on retatrutide, but Lilly spent a good chunk of time on how they're positioning it. They reminded investors that tirzepatide is becoming foundational, but retatrutide is built for people who don't hit their goals on tirz alone, especially those with BMI over 35.
The first Phase 3 trial to read out will be TRIUMPH-4, which is focused on osteoarthritis pain. It's a short study and not optimized for weight loss readout. TRIUMPH-1 is the one to watch if you're looking for max efficacy signals.
They also reiterated that retatrutide's trial design allows for simultaneous approval in obesity, sleep apnea, and osteoarthritis, depending on how the data land.
Eloralintide data show real weight loss with low nausea
Eloralintide, the selective amylin receptor agonist, led to up to 11.3 percent weight loss in 12 weeks in people without diabetes. One dose level saw nearly 9% loss with no nausea or vomiting at all. It's a once-weekly injection, and Lilly emphasized that the GI tolerability may be better than dual amylin-calcitonin agonists like cagrilintide.
Phase 2 trials are underway testing eloralintide on its own and in combination with tirzepatide. The first of those will read out later this year.
Bimagrumab is being tested with tirzepatide in subcutaneous form
Bimagrumab, which blocks activin and myostatin pathways, is in Phase 2. The BELIEVE study tested it with semaglutide as an IV infusion. The plan now is to move to once-weekly subcutaneous dosing and pair it with tirzepatide.
Lilly's framing bimagrumab as an orthogonal mechanism that could drive healthier weight loss, burning fat while preserving or increasing muscle mass. The company called out older adults and people with heart failure as possible use cases.
We'll get more from the BELIEVE data later this week.
SURPASS-CVOT still expected Q3, with data locked by EASD
They haven't seen the data yet, but confirmed it will be ready in time for the already-announced EASD symposium.
They reiterated the design: a head-to-head trial comparing tirzepatide to dulaglutide, both delivered via identical auto-injectors to keep blinding intact. The FDA's non-inferiority margin is set at 1.05, and Lilly said that a hazard ratio of 0.9 or better should meet the bar for superiority.
They were clear that even non-inferiority would be enough to get a cardiovascular indication, and that dulaglutide already has CV risk reduction baked in from REWIND. If tirz beats dulaglutide, that's a major statement for the entire class.
On affordability, they said nothing, but signaled everything
When asked directly how they plan to launch orforglipron without cannibalizing Mounjaro and Zepbound, Lilly didn't answer. But they gave hints.
They talked about positioning orforglipron earlier in the treatment continuum. They pointed out the separate manufacturing. They mentioned employers and payers will eventually realize they're already paying for obesity, just through hospitalizations and ER visits instead of medication.
All signs point to orforglipron being priced for scale. But the only price that matters is the one people pay at the pharmacy counter. That piece is still unknown.
Bottom line
This wasn't a science presentation. It was a signal to investors that Lilly intends to lead this space all the way through the decade. They're not replacing tirzepatide. They're building around it. Orforglipron for scale. Retatrutide for the ceiling. Eloralintide for tolerability. Bimagrumab for composition. And tirzepatide at the center".
© 2025 David Knapp
On The Pen, PO Box 541, Cedar Falls, IA 50613
https://www.onthepen.com/
Jun 23
"We're knee-deep in ADA 85 coverage, but Lilly just did something they rarely do. They held a special investor event during the conference. And if you've been following the GLP-1 space closely, this wasn't about surprising us with new molecules. It was about signaling to Wall Street that Lilly is building for the long game, and laying out the clearest roadmap yet for what happens next with orforglipron, retatrutide, eloralintide, and bimagrumab.
If you missed the call, here's what actually mattered.
Orforglipron is still on track for obesity filing this year
ACHIEVE-1 confirmed what most of us already expected. Orforglipron, Lilly's once-daily oral GLP-1, delivered a 1.6%ent A1C reduction and just under 8% body weight loss over 40 weeks in people with type 2 diabetes. That puts it on par with early SURPASS numbers and sets the stage for ATTAIN-1, which will show the weight loss side in people without diabetes. Those results are expected later this quarter.
The call reaffirmed that Lilly plans to file for obesity first, with type 2 diabetes following in 2026. The delay isn't strategic, it's because the diabetes guidance requires 24 months of exposure versus 18 for obesity.
They also mentioned ongoing trials looking at orforglipron in maintenance dosing, obstructive sleep apnea, and hypertension. And they made a point to emphasize that orforglipron uses a separate manufacturing footprint, doesn't require cold chain, and won't pull supply from injectables. They're clearly positioning it as the scalable option for global reach.
GI side effects weren't out of bounds
Lilly addressed the diarrhea concerns directly. Rates were highest in India and China, lowest in Japan, and midrange in the U.S. They chalked it up to geographic and dietary differences. At the highest dose, fewer than 6 percent of patients discontinued due to GI issues. That's lower than what's been reported in many GLP-1 trials.
There were no Hy's Law cases, and liver enzymes remained stable, even among people who entered the trial with transaminase levels up to five times the upper limit of normal. Lilly wanted to be clear on this point: they are not seeing signs of hepatotoxicity.
Retatrutide is still being framed as the next tier for high-BMI patients
We didn't get new data on retatrutide, but Lilly spent a good chunk of time on how they're positioning it. They reminded investors that tirzepatide is becoming foundational, but retatrutide is built for people who don't hit their goals on tirz alone, especially those with BMI over 35.
The first Phase 3 trial to read out will be TRIUMPH-4, which is focused on osteoarthritis pain. It's a short study and not optimized for weight loss readout. TRIUMPH-1 is the one to watch if you're looking for max efficacy signals.
They also reiterated that retatrutide's trial design allows for simultaneous approval in obesity, sleep apnea, and osteoarthritis, depending on how the data land.
Eloralintide data show real weight loss with low nausea
Eloralintide, the selective amylin receptor agonist, led to up to 11.3 percent weight loss in 12 weeks in people without diabetes. One dose level saw nearly 9% loss with no nausea or vomiting at all. It's a once-weekly injection, and Lilly emphasized that the GI tolerability may be better than dual amylin-calcitonin agonists like cagrilintide.
Phase 2 trials are underway testing eloralintide on its own and in combination with tirzepatide. The first of those will read out later this year.
Bimagrumab is being tested with tirzepatide in subcutaneous form
Bimagrumab, which blocks activin and myostatin pathways, is in Phase 2. The BELIEVE study tested it with semaglutide as an IV infusion. The plan now is to move to once-weekly subcutaneous dosing and pair it with tirzepatide.
Lilly's framing bimagrumab as an orthogonal mechanism that could drive healthier weight loss, burning fat while preserving or increasing muscle mass. The company called out older adults and people with heart failure as possible use cases.
We'll get more from the BELIEVE data later this week.
SURPASS-CVOT still expected Q3, with data locked by EASD
They haven't seen the data yet, but confirmed it will be ready in time for the already-announced EASD symposium.
They reiterated the design: a head-to-head trial comparing tirzepatide to dulaglutide, both delivered via identical auto-injectors to keep blinding intact. The FDA's non-inferiority margin is set at 1.05, and Lilly said that a hazard ratio of 0.9 or better should meet the bar for superiority.
They were clear that even non-inferiority would be enough to get a cardiovascular indication, and that dulaglutide already has CV risk reduction baked in from REWIND. If tirz beats dulaglutide, that's a major statement for the entire class.
On affordability, they said nothing, but signaled everything
When asked directly how they plan to launch orforglipron without cannibalizing Mounjaro and Zepbound, Lilly didn't answer. But they gave hints.
They talked about positioning orforglipron earlier in the treatment continuum. They pointed out the separate manufacturing. They mentioned employers and payers will eventually realize they're already paying for obesity, just through hospitalizations and ER visits instead of medication.
All signs point to orforglipron being priced for scale. But the only price that matters is the one people pay at the pharmacy counter. That piece is still unknown.
Bottom line
This wasn't a science presentation. It was a signal to investors that Lilly intends to lead this space all the way through the decade. They're not replacing tirzepatide. They're building around it. Orforglipron for scale. Retatrutide for the ceiling. Eloralintide for tolerability. Bimagrumab for composition. And tirzepatide at the center".
© 2025 David Knapp
On The Pen, PO Box 541, Cedar Falls, IA 50613
https://www.onthepen.com/
