CagriSema falls short of Zepbound in phase 3 head-to-head, sending Novo Nordisk shares sharply lower

cygnus

cygnus

Explorer
Joined
Dec 16, 2025
Messages
18
Reaction score
0
Location
Phoenix/Arizona/United States
In a direct phase 3 comparison, Novo Nordisk's investigational obesity treatment CagriSema did not beat Eli Lilly's Zepbound, and Novo Nordisk shares dropped sharply as a result. At 84 weeks, CagriSema produced 23% weight loss, whereas Zepbound (tirzepatide) reached 25.5%. This result strengthens Zepbound's standing as a leader in the weight loss market.



103d94d87199a48730c9f0dae940ca606789fa62c17841c8ff1351fc5a1fb35d.jpg




Novo Nordisk sinks 16% after weight loss drug fails to match Eli Lilly's in trial



On Monday, Novo Nordisk stock declined more than 16% following the company's announcement that its next-generation weight loss drug missed its primary endpoint.

Image unavailable


www.cnbc.com
 
A 23.3% result still carries real weight. Sure, it won't win any BP Wars, but from the patient's perspective, that figure matters.
 
Body weight differences across the groups are basically identical. It would be great if these trials included Dexa Scans to show what portion of the lost weight comes from fat versus muscle. Given that roughly 25% of body weight lost is muscle, that information matters far more in clinical terms than total body weight reduction.
 
CagriReta is the real deal!

My current routine: 4.25mg of reta every week, injected on Sunday, plus 750mcg of cagri each week on Wednesday. This pairing has been giving me good results.
 
On paper the gap isn't huge, yet the tolerability profiles will diverge considerably, and Tirz comes out ahead.

Sema had first-mover status, but it's been superseded. Cagri brought something new, though it isn't a selective amylin agonist. Selective amylin agonists such as Elora are now understood to carry far gentler side effects. That makes CagriSema a franken-GLP with compromises baked in.

Like the OP pointed out, pairing Reta with an amylin agonist such as Elora could be the combo to beat...assuming your goal is to shrink down to your birth weight.
 
Sema hasn't been made obsolete. Yes, newer options have come along, but it still does the job. Talk to anyone who continues to take it or who combines it with something else. Sure, it isn't the newest or the best anymore. Even so, people keep using it—it remains 1 option among many.
 
MeedzMoar said:

Sema hasn't been made obsolete. Yes, newer options have come along, but it still does the job. Talk to anyone who continues to take it or who combines it with something else. Sure, it isn't the newest or the best anymore. Even so, people keep using it—it remains 1 option among many.
Click to expand...
For certain individuals—like a friend of mine who experienced allergic reactions to triz—this represents a viable alternative that works well and carries no risk for them.
 
Ragnar said:

Body weight differences across the groups are basically identical. It would be great if these trials included Dexa Scans to show what portion of the lost weight comes from fat versus muscle. Given that roughly 25% of body weight lost is muscle, that information matters far more in clinical terms than total body weight reduction.
Click to expand...
More and more voices — physicians as well as obesity specialists — are telling me that what gets lost isn't strictly muscle tissue but rather the fat stored within the muscle. Another finding is that strength doesn't decline, which is a promising sign. Everything here still requires further study and it's premature to draw conclusions. If it does turn out to be accurate, it won't surprise me.
 
Why isn't anyone combining a myostatin inhibitor with a GLP-1 agonist, so that muscle mass is preserved or even built up while fat is being lost?
 
SpiralJetty said:

Why isn't anyone combining a myostatin inhibitor with a GLP-1 agonist, so that muscle mass is preserved or even built up while fat is being lost?
Click to expand...
As of now, no myostatin inhibitor has been approved, and none has proven both safe and effective. A lot of us are waiting impatiently for one. From what I know, 3 candidates are in the pipeline, though all are monoclonal antibodies—meaning they'll carry a high price tag and won't show up as grey-market products anytime soon. A few peptides are sold claiming to do the job, but their safety and results are dubious. For the time being, enobosarm (Ostarine) has been studied alongside Sema, and it seems to help users preserve muscle while losing primarily fat. If I recall correctly, that was a small phase 1 trial using 3 mg. Still, Ostarine comes with liver and lipid side effects that need monitoring.
 
Sorry to those holding Novo Nordisk stock. I took part in this trial on the tirzepatide arm, and I dropped 30.1% of my bodyweight while also getting completely yoked from lifting.
 
Sema remains a favorite of mine, no question.

Right now I’m on week 3 of 3 mg Sema alongside 10 mg Reta — absolute perfection 🤌

Honestly, when it comes to curbing appetite, I don’t see much difference among GLP drugs. Tirz and Reta might edge ahead since they ramp up energy expenditure, though in my view the gap isn’t large.

All I’m saying: if Reta were not around today, sticking with Sema alone would suit me just fine.

Obsolete? Sema? I wouldn’t say that. It’s more that its popularity has dipped — and that works in my favor, because it means I can keep using Sema at a lower cost 😁
 
Sparky757 said:

Sorry to those holding Novo Nordisk stock. I took part in this trial on the tirzepatide arm, and I dropped 30.1% of my bodyweight while also getting completely yoked from lifting.
Click to expand...
Speaking as someone holding LLY stock, I don't hold a grudge. What bothers me is that Lilly didn't get an instant boost when Nova's share price dropped.
 
Sparky757 said:

Sorry to those holding Novo Nordisk stock. I took part in this trial on the tirzepatide arm, and I dropped 30.1% of my bodyweight while also getting completely yoked from lifting.
Click to expand...
Haha, I hold plenty of LLY, so I'm fine.
 
94brian49 said:

Sema remains a favorite of mine, no question.

Right now I’m on week 3 of 3 mg Sema alongside 10 mg Reta — absolute perfection 🤌

Honestly, when it comes to curbing appetite, I don’t see much difference among GLP drugs. Tirz and Reta might edge ahead since they ramp up energy expenditure, though in my view the gap isn’t large.

All I’m saying: if Reta were not around today, sticking with Sema alone would suit me just fine.

Obsolete? Sema? I wouldn’t say that. It’s more that its popularity has dipped — and that works in my favor, because it means I can keep using Sema at a lower cost 😁
Click to expand...
Same here. Stacking GLP/GIPs isn't something I'm prepared to do. Sema worked well for me until I hit the ceiling. I wish I had known back then about the higher dosing trials. As it stands, I've got a good supply of Tz for a while.
 
94brian49 said:

Sema remains a favorite of mine, no question.

Right now I’m on week 3 of 3 mg Sema alongside 10 mg Reta — absolute perfection 🤌

Honestly, when it comes to curbing appetite, I don’t see much difference among GLP drugs. Tirz and Reta might edge ahead since they ramp up energy expenditure, though in my view the gap isn’t large.

All I’m saying: if Reta were not around today, sticking with Sema alone would suit me just fine.

Obsolete? Sema? I wouldn’t say that. It’s more that its popularity has dipped — and that works in my favor, because it means I can keep using Sema at a lower cost 😁
Click to expand...
A lot of folks are always chasing whatever is newest and flashiest
 
Back
Top