Lilly's oral GLP-1, orforglipron, delivered superior
blood sugar control and
weight loss compared to oral
semaglutide in head-to-head
type 2 diabetes trial
published in The Lancet
(INDIANAPOLIS) - Lilly
(NYSE: LLY) announces
detailed results from
ACHIEVE-3, the first
head-to-head Phase 3 trial
evaluating the safety and
efficacy of orforglipron, a
small molecule oral GLP-1
without food or water
restrictions, compared with
oral semaglutide in adults
with type 2 diabetes
inadequately controlled with
metformin. The 52-week trial
enrolled 1,698 participants
across four treatment arms:
orforglipron 12 mg and 36
mg, and oral semaglutide 7
mg and 14 mg. In ACHIEVE-3,
orforglipron outperformed
oral semaglutide across the
primary and all key
secondary endpoints,
delivering significantly
greater improvements in A1C
and weight. The results were
published today in The
Lancet.
"ACHIEVE-3
gives us the first
head-to-head comparison
between two oral GLP-1
receptor agonist therapies
in adults with type 2
diabetes, and the
differences were clinically
meaningful," said Dr. Julio
Rosenstock, clinical
professor of medicine at the
University of Texas
Southwestern Medical Center
and lead investigator.
"Orforglipron 12 mg and 36
mg doses outperformed oral
semaglutide 7 mg and 14 mg
diabetes-related doses on
every key endpoint we
measured, including A1C and
weight loss, with
improvements appearing as
early as four weeks and
sustained throughout the
study."
ACHIEVE-3 Full Results
Orforglipron also showed
clinically meaningful
improvements from baseline
across key cardiovascular
risk factors, including
non-HDL cholesterol, HDL
cholesterol, VLDL
cholesterol, total
cholesterol, systolic blood
pressure, and
triglycerides.4
"The
results of ACHIEVE-3
highlight the potential
advantages of orforglipron
over oral semaglutide for
type 2 diabetes: greater A1C
reduction, more weight loss,
and the ability to take it
without food or water timing
restrictions — that's a
combination that could
matter significantly to
people managing their
disease day in and day out,"
said Kenneth Custer,
Ph.D., executive vice
president and president of
Lilly Cardiometabolic Health.
"With global submissions
underway and FDA action on
obesity expected next
quarter, we're focused on
making this option available
as quickly as possible."
The overall safety and
tolerability profile of
orforglipron in ACHIEVE-3
was consistent with previous
trials. For orforglipron and
oral semaglutide, the most
common adverse events were
nausea, diarrhea, vomiting,
dyspepsia and decreased
appetite. Treatment
discontinuation rates due to
adverse events were 8.7% (12
mg) and 9.7% (36 mg) for
orforglipron vs. 4.5% (7 mg)
and 4.9% (14 mg) for oral
semaglutide.
Lilly
has submitted orforglipron
to regulators in over 40
countries, with submission
for type 2 diabetes in the
U.S. planned later this
year.
