Experimental Lilly combination drug tops Zepbound in weight-loss trial

Novo Nordisk A/S

30/09/2026 15:15

    * Lilly says combo drug EloraTZP cut 23.3% of body weight vs
14.8% for Zepbound alone
    * Company says patient discontinuation rates hit as high as
27% on combo therapy vs 2.9% for tirzepatide alone
    * Lilly targets late-stage trial start for EloraTZP in
fourth quarter of 2026

    By Patrick Wingrove
       Sept 30 (Reuters) - Eli Lilly  LLY.N  said on Wednesday
its experimental combination weight-loss drug outperformed its
blockbuster Zepbound in a head-to-head trial, intensifying the
competition with Danish rival Novo Nordisk  NOVOb.CO  for new,
more effective obesity therapies.
    The Indianapolis-based drugmaker said patients with diabetes
on the highest tested dose of EloraTZP, which combines
tirzepatide and experimental drug eloralintide, lost an average
of 23.3% of body weight over 48 weeks. That compared with 14.8%
for patients on the highest dose of Zepbound in the mid-stage
trial.
    Tirzepatide is the active ingredient in Zepbound as well as
Lilly's diabetes drug Mounjaro.
    Kenneth Custer, president of Lilly's cardiometabolic health
division, said in an interview that he expected the combo drug
would offer "the best balance of efficacy, safety,
and tolerability" within Lilly's obesity portfolio and among
competitors.
    He noted that the treatment produced significant weight loss
in patients with diabetes, a group that historically faces
greater challenges with weight management.
    Custer said it was possible the combination could produce
even greater weight loss in later trials than retatrutide,
another promising Lilly experimental obesity medication. In a
late-stage trial, the highest dose of retatrutide drove an
average weight reduction of up to 28.3% over 80 weeks in
patients without diabetes. 
    EloraTZP also cut blood sugar levels, lowering A1C by up to
2.9% versus 2.4% for tirzepatide alone, according to data
presented at the European Association for the Study of Diabetes
meeting in Milan.
    Patients stopped taking EloraTZP in the trial at a rate of
10.8% to 27% depending on the severity of their side effects as
multiple doses were tested. That compared with a dropout rate of
0% to 10.8% with eloralintide alone, 2.9% for tirzepatide and
16.7% for those who received a placebo.
    The most common side effects were mild to moderate
gastrointestinal issues that occurred mainly during dose
escalation and were more frequent in the combination arms than
with either drug alone, the company said. 
    Lilly, in a press conference to discuss the results, said
the higher discontinuation rate was due to patients ramping up
doses of two drugs at once. It said the company will
improve escalation schedules in longer, late-stage trials.
     
     COMPETITIVE LANDSCAPE
    The results raise the stakes in a fight between Lilly and
Novo for share of the global weight-loss market forecast by some
analysts to reach $100 billion to $150 billion annually by the
end of the decade. 
    Novo is on track to launch the first combination obesity
drug, CagriSema, early next year. Expectations for that
medication took a hit in February when it fell short of Lilly's
high-dose tirzepatide in a head-to-head trial, despite achieving
a 23% average weight reduction over 84 weeks.
    Novo's ​fortunes have reversed sharply from its days of
dominating the market with the 2021 arrival of powerful obesity
drug Wegovy that propelled its valuation above $600 billion. The
Danish drugmaker's shares have tumbled ⁠more than 70% from their
record highs in the face of stiff competition from US rival
Lilly.
    Eli Lilly executives said it was too early to determine the
ideal patient profile for its combination therapy, but noted it
could serve individuals needing 20% to 30% weight loss, or those
who fail to achieve their goals on Zepbound, by targeting a
hormone pathway linked to hunger and thoughts about food.
    Eloralintide belongs to a class of drugs known as selective
amylin receptor agonists, which target a different hormone than
GLP-1 Zepbound.
    In the multi-arm EloraTZP trial of 367 obese or overweight
adults with type 2 diabetes in the US and Argentina,
eloralintide alone led to an average weight loss of 12.3% on the
second highest dose tested, and 11.1% on the highest, while
those taking a placebo lost just 3%.
    The company said it plans to start late-stage trials
for EloraTZP in the fourth quarter of 2026, while late-stage
trials of eloralintide in obese and overweight patients with and
without diabetes were ongoing. 
    "Obesity and type 2 diabetes are interconnected, and we are
seeing the potential benefit of targeting multiple hormonal
pathways to address both," said Liana Billings, the study's lead
researcher.
     
     

    (Reporting by Patrick Wingrove in London; Editing by
Caroline Humer and Bill Berkrot)