176-week SURMOUNT-1 Phase 3 study in adults
with pre-diabetes is the longest completed trial of tirzepatide to
date
Tirzepatide resulted in sustained weight loss
through the treatment period, averaging a 22.9% decrease in body
weight with the 15 mg dose at end of treatment
Results are consistent with the combined
pharmacology of GIP and GLP-1 receptor agonism
INDIANAPOLIS, Aug. 20,
2024 /PRNewswire/ -- Eli Lilly and Company (NYSE:
LLY) announced today positive topline results from the SURMOUNT-1
three-year study (176-week treatment period) evaluating the
efficacy and safety of tirzepatide (Zepbound® and
Mounjaro®) once weekly for long-term weight management
and delay in progression to diabetes in adults with pre-diabetes
and obesity or overweight. Weekly tirzepatide injections (5
mgi, 10 mg, 15 mg) significantly reduced the risk of
progression to type 2 diabetes by 94% ii among adults
with pre-diabetes and obesity or overweight compared to placebo.
Additionally, treatment with tirzepatide resulted in sustained
weight loss through the treatment period, with adults on the 15 mg
dose experiencing a 22.9% ii average decrease in body
weight compared to 2.1% for placebo in adults with pre-diabetes and
obesity or overweight at the end of the treatment period.
"Obesity is a chronic disease that puts nearly 900 million
adults worldwide at an increased risk of other complications such
as type 2 diabetes," said Jeff
Emmick, M.D., Ph.D., senior vice president, product
development, Lilly. "Tirzepatide reduced the risk of developing
type 2 diabetes by 94% and resulted in sustained weight loss over
the three-year treatment period. These data reinforce the potential
clinical benefits of long-term therapy for people living with
obesity and pre-diabetes."
Tirzepatide was evaluated in 1,032 adults who had pre-diabetes
at randomization and obesity or overweight for a treatment period
of 176 weeks, followed by a 17-week off-treatment period (193 weeks
in total). Results from the SURMOUNT-1 phase 3 study's primary
analysis at 72 weeks in all participants were published in the
New England Journal of Medicine in 2022.
In a key secondary endpoint, tirzepatide led to a significant
reduction in the risk of progression to type 2 diabetes in adults
with pre-diabetes and obesity or overweight from baseline to week
176 (p<0.0001, controlled for type 1 error). For the efficacy
estimandii, pooled doses of tirzepatide achieved
significant results, demonstrating a 94% reduction in risk of
progression to type 2 diabetes compared to placebo up to week 176.
For the treatment-regimen estimandiii, pooled doses of
tirzepatide resulted in a significant 93% reduction in risk of
progression to type 2 diabetes compared to placebo up to week
176.
In an additional key secondary endpoint, tirzepatide (10 mg and
15 mg) led to statistically significant weight reduction compared
to placebo in adults with pre-diabetes and obesity or overweight
from baseline to week 176 (p<0.001, controlled for type 1
error). For the efficacy estimandii, adults taking
tirzepatide achieved average weight reductions of 15.4% (5
mgi), 19.9% (10 mg) and 22.9% (15 mg) compared to
placebo (2.1%) at week 176. For the treatment-regimen
estimandiii, adults taking tirzepatide achieved average
weight reductions of 12.3% (5 mg i), 18.7% (10 mg) and
19.7% (15 mg) compared to placebo (1.3%) at week 176.
During the 17-week off-treatment follow-up period, those who had
discontinued from tirzepatide began to regain weight and had some
increase in the progression to type 2 diabetes, resulting in an 88%
reduction (p<0.0001, controlled for type 1 error) in the risk of
progression to type 2 diabetes compared to placebo.
The overall safety and tolerability profile of tirzepatide over
the 193-week study was consistent with the previously published
primary results at 72 weeks in SURMOUNT-1 and other tirzepatide
clinical studies conducted for chronic weight management. The most
frequently reported adverse events were typically
gastrointestinal-related and generally mild to moderate in
severity. The most common gastrointestinal-related adverse events
for patients treated with tirzepatide were diarrhea, nausea,
constipation and vomiting.
Tirzepatide, a GIP and GLP-1 receptor agonist, works by
activating the two hormone receptors. GLP-1 is a regulator of
appetite and caloric intake. Nonclinical studies suggest the
addition of GIP may further contribute to the regulation of food
intake. Tirzepatide decreases calorie intake, and the effects are
likely mediated by affecting appetite. In addition, tirzepatide
stimulates insulin secretion in a glucose-dependent manner.
Tirzepatide increases insulin sensitivity in patients with type 2
diabetes mellitus and these effects can lead to a reduction of
blood glucose.
These topline results provide evidence for reduced risk of
progression to type 2 diabetes and long-term maintenance of weight
loss with tirzepatide in adults with pre-diabetes and obesity or
overweight. Detailed results will be submitted to a peer-reviewed
journal and presented at ObesityWeek 2024, which will take place
November 3-6.
About SURMOUNT-1
SURMOUNT-1 (NCT04184622) was a
multi-center, randomized, double-blind, parallel,
placebo-controlled trial comparing the efficacy and safety of
tirzepatide 5 mg, 10 mg and 15 mg to placebo as an adjunct to a
reduced-calorie diet and increased physical activity in adults
without type 2 diabetes who have obesity, or overweight with at
least one of the following comorbidities: hypertension,
dyslipidemia, obstructive sleep apnea (OSA) or cardiovascular
disease. The 1,032 participants who had pre-diabetes at study
commencement remained enrolled in SURMOUNT-1 for an additional 104
weeks of treatment following the initial 72-week completion date to
evaluate the impact on body weight and potential differences in
progression to type 2 diabetes at three years of treatment with
tirzepatide compared to placebo.
About tirzepatide
Tirzepatide is a once-weekly GIP
(glucose-dependent insulinotropic polypeptide) receptor and GLP-1
(glucagon-like peptide-1) receptor agonist. Tirzepatide is a single
molecule that activates the body's receptors for GIP and GLP-1,
which are natural incretin hormones. Both GIP and GLP-1 receptors
are found in areas of the human brain important for appetite
regulation. Tirzepatide has been shown to decrease food intake and
modulate fat utilization. Studies of tirzepatide in chronic kidney
disease (CKD) and in morbidity/mortality in obesity (MMO) are also
ongoing. Lilly submitted data for tirzepatide in moderate-to-severe
obstructive sleep apnea (OSA) and obesity to the U.S. Food and Drug
Administration (FDA) and other global regulatory agencies earlier
this year. Lilly plans to submit data for tirzepatide in heart
failure with preserved ejection fraction (HFpEF) and obesity to the
U.S. FDA and other global regulatory agencies later this year.
Tirzepatide was approved by the U.S. FDA as
Mounjaro® for adults with type 2 diabetes to improve
glycemic control on May 13, 2022, and
as Zepbound® for adults with obesity (a BMI of 30 kg/m2
or greater) or those who are overweight (a BMI of 27 kg/m2 or
greater) who also have a weight-related comorbid condition on
November 8, 2023. Tirzepatide is also
commercialized as Mounjaro® in some global markets
outside the U.S. for adults with obesity or those who are
overweight who also have a weight-related comorbid condition.
Tirzepatide is the only approved GIP (glucose-dependent
insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1)
treatment for chronic weight management. Both Mounjaro®
and Zepbound® should be used as an adjunct to diet and
exercise.
INDICATION AND SAFETY SUMMARY WITH WARNINGS
Zepbound® (ZEHP-bownd) is an injectable
prescription medicine that may help adults with obesity, or with
excess weight (overweight) who also have weight-related medical
problems, lose weight and keep it off. It should be used with
a reduced-calorie diet and increased physical activity.
- Zepbound contains tirzepatide and should not be used with
other tirzepatide-containing products or any GLP-1 receptor
agonist medicines. It is not known if Zepbound is safe and
effective when taken with other prescription, over-the-counter, or
herbal weight loss products. It is not known if Zepbound can be
used in people who have had pancreatitis. It is not known if
Zepbound is safe and effective for use in children under 18 years
of age.
Warnings - Zepbound may cause tumors in the thyroid,
including thyroid cancer. Watch for possible symptoms, such as a
lump or swelling in the neck, hoarseness, trouble swallowing, or
shortness of breath. If you have any of these symptoms, tell your
healthcare provider.
- Do not use Zepbound if you or any of your family have ever had
a type of thyroid cancer called medullary thyroid carcinoma
(MTC).
- Do not use Zepbound if you have Multiple Endocrine Neoplasia
syndrome type 2 (MEN 2).
- Do not use Zepbound if you have had a serious allergic reaction
to tirzepatide or any of the ingredients in Zepbound.
Zepbound may cause serious side effects, including:
Severe stomach problems. Stomach problems, sometimes
severe, have been reported in people who use Zepbound. Tell your
healthcare provider if you have stomach problems that are severe or
will not go away.
Kidney problems (kidney failure). Diarrhea, nausea,
and vomiting may cause a loss of fluids (dehydration), which may
cause kidney problems. It is important for you to drink fluids to
help reduce your chance of dehydration.
Gallbladder problems. Gallbladder problems have happened
in some people who use Zepbound. Tell your healthcare provider
right away if you get symptoms of gallbladder problems, which may
include pain in your upper stomach (abdomen), fever, yellowing of
skin or eyes (jaundice), or clay-colored stools.
Inflammation of the pancreas (pancreatitis). Stop using
Zepbound and call your healthcare provider right away if you have
severe pain in your stomach area (abdomen) that will not go away,
with or without vomiting. You may feel the pain from your abdomen
to your back.
Serious allergic reactions. Stop using Zepbound and get
medical help right away if you have any symptoms of a serious
allergic reaction, including swelling of your face, lips, tongue or
throat, problems breathing or swallowing, severe rash or itching,
fainting or feeling dizzy, or very rapid heartbeat.
Low blood sugar (hypoglycemia). Your risk for getting low
blood sugar may be higher if you use Zepbound with medicines that
can cause low blood sugar, such as a sulfonylurea or insulin.
Signs and symptoms of low blood sugar may include dizziness
or light-headedness, sweating, confusion or drowsiness, headache,
blurred vision, slurred speech, shakiness, fast heartbeat, anxiety,
irritability, mood changes, hunger, weakness or feeling
jittery.
Changes in vision in patients with type 2 diabetes. Tell
your healthcare provider if you have changes in vision during
treatment with Zepbound.
Depression or thoughts of suicide. You should pay
attention to changes in your mood, behaviors, feelings or thoughts.
Call your healthcare provider right away if you have any mental
changes that are new, worse, or worry you.
Common side effects
The most common side effects of Zepbound include nausea,
diarrhea, vomiting, constipation, stomach (abdominal) pain,
indigestion, injection site reactions, feeling tired, allergic
reactions, belching, hair loss, and heartburn. These are not all
the possible side effects of Zepbound. Talk to your healthcare
provider about any side effect that bothers you or doesn't go
away.
Tell your healthcare provider if you have any side effects.
You can report side effects at 1-800-FDA-1088 or
www.fda.gov/medwatch.
Before using Zepbound
- Your healthcare provider should show you how to use Zepbound
before you use it for the first time.
- Tell your healthcare provider if you are taking medicines to
treat diabetes including insulin or sulfonylureas which could
increase your risk of low blood sugar. Talk to your healthcare
provider about low blood sugar levels and how to manage
them.
- If you take birth control pills by mouth, talk to your
healthcare provider before you use Zepbound. Birth control pills
may not work as well while using Zepbound. Your healthcare
provider may recommend another type of birth control for 4 weeks
after you start Zepbound and for 4 weeks after each increase in
your dose of Zepbound.
Review these questions with your healthcare provider:
❑ Do you have other medical conditions,
including problems with your pancreas or kidneys, or severe
problems with your stomach, such as slowed emptying of your stomach
(gastroparesis) or problems digesting food?
❑ Do you take diabetes medicines, such as insulin or
sulfonylureas?
❑ Do you have a history of diabetic retinopathy?
❑ Do you take any other prescription medicines or
over-the-counter drugs, vitamins, or herbal supplements?
❑ Are you pregnant, plan to become pregnant, breastfeeding,
or plan to breastfeed? Zepbound may harm your unborn baby. Tell
your healthcare provider if you become pregnant while using
Zepbound. It is not known if Zepbound passes into your breast milk.
You should talk with your healthcare provider about the best way to
feed your baby while using Zepbound.
- Pregnancy Exposure Registry: There will be a
pregnancy exposure registry for women who have taken Zepbound
during pregnancy. The purpose of this registry is to collect
information about the health of you and your baby. Talk to your
healthcare provider about how you can take part in this registry,
or you may contact Lilly at 1-800-LillyRx (1-800-545-5979).
How to take
- Read the Instructions for Use that come with
Zepbound.
- Use Zepbound exactly as your healthcare provider says.
- Zepbound is injected under the skin (subcutaneously) of your
stomach (abdomen), thigh, or upper arm.
- Use Zepbound 1 time each week, at any time of the
day.
- Change (rotate) your injection site with each weekly injection.
Do not use the same site for each injection.
- If you take too much Zepbound, call your healthcare provider,
seek medical advice promptly, or contact a Poison Center expert
right away at 1-800-222-1222.
Learn more
Zepbound is a prescription medicine. For more information, call
1-800-LillyRx (1-800-545-5979) or go to
www.zepbound.lilly.com.
This summary provides basic information about Zepbound but does
not include all information known about this medicine. Read the
information that comes with your prescription each time your
prescription is filled. This information does not take the place of
talking with your healthcare provider. Be sure to talk to your
healthcare provider about Zepbound and how to take it. Your
healthcare provider is the best person to help you decide if
Zepbound is right for you.
ZP CON CBS 08NOV2023
Zepbound® and its delivery device base are
registered trademarks owned or licensed by Eli Lilly and Company,
its subsidiaries, or affiliates.
INDICATION AND SAFETY SUMMARY WITH WARNINGS
Mounjaro® (mown-JAHR-OH) is an injectable
medicine for adults with type 2 diabetes used along with diet and
exercise to improve blood sugar (glucose).
- It is not known if Mounjaro can be used in people who have had
inflammation of the pancreas (pancreatitis). Mounjaro is not for
use in people with type 1 diabetes. It is not known if Mounjaro is
safe and effective for use in children under 18 years of age.
Warnings - Mounjaro may cause tumors in the thyroid,
including thyroid cancer. Watch for possible symptoms, such as a
lump or swelling in the neck, hoarseness, trouble swallowing, or
shortness of breath. If you have any of these symptoms, tell your
healthcare provider.
- Do not use Mounjaro if you or any of your family have ever had
a type of thyroid cancer called medullary thyroid carcinoma
(MTC).
- Do not use Mounjaro if you have Multiple Endocrine Neoplasia
syndrome type 2 (MEN 2).
- Do not use Mounjaro if you are allergic to it or any of the
ingredients in Mounjaro.
Mounjaro may cause serious side effects, including:
Inflammation of the pancreas (pancreatitis). Stop using
Mounjaro and call your healthcare provider right away if you have
severe pain in your stomach area (abdomen) that will not go away,
with or without vomiting. You may feel the pain from your abdomen
to your back.
Low blood sugar (hypoglycemia). Your risk for getting low
blood sugar may be higher if you use Mounjaro with another medicine
that can cause low blood sugar, such as a sulfonylurea or insulin.
Signs and symptoms of low blood sugar may include dizziness
or light-headedness, sweating, confusion or drowsiness, headache,
blurred vision, slurred speech, shakiness, fast heartbeat, anxiety,
irritability, or mood changes, hunger, weakness and feeling
jittery.
Serious allergic reactions. Stop using Mounjaro and get
medical help right away if you have any symptoms of a serious
allergic reaction, including swelling of your face, lips, tongue or
throat, problems breathing or swallowing, severe rash or itching,
fainting or feeling dizzy, and very rapid heartbeat.
Kidney problems (kidney failure). In people who have
kidney problems, diarrhea, nausea, and vomiting may cause a loss of
fluids (dehydration), which may cause kidney problems to get worse.
It is important for you to drink fluids to help reduce your chance
of dehydration.
Severe stomach problems. Stomach problems, sometimes
severe, have been reported in people who use Mounjaro. Tell your
healthcare provider if you have stomach problems that are severe or
will not go away.
Changes in vision. Tell your healthcare provider if you
have changes in vision during treatment with Mounjaro.
Gallbladder problems. Gallbladder problems have
happened in some people who use Mounjaro. Tell your healthcare
provider right away if you get symptoms of gallbladder problems,
which may include pain in your upper stomach (abdomen), fever,
yellowing of skin or eyes (jaundice), and clay-colored stools.
Common side effects
The most common side effects of Mounjaro include nausea,
diarrhea, decreased appetite, vomiting, constipation, indigestion,
and stomach (abdominal) pain. These are not all the possible side
effects of Mounjaro. Talk to your healthcare provider about any
side effect that bothers you or doesn't go away.
Tell your healthcare provider if you have any side effects.
You can report side effects at 1-800-FDA-1088 or
www.fda.gov/medwatch.
Before using Mounjaro
- Your healthcare provider should show you how to use Mounjaro
before you use it for the first time.
- Talk to your healthcare provider about low blood sugar and
how to manage it.
- If you take birth control pills by mouth, talk to your
healthcare provider before you use Mounjaro. Birth control pills
may not work as well while using Mounjaro. Your healthcare
provider may recommend another type of birth control for 4 weeks
after you start Mounjaro and for 4 weeks after each increase in
your dose of Mounjaro.
Review these questions with your healthcare provider:
❑ Do you have other medical conditions,
including problems with your pancreas or kidneys, or severe
problems with your stomach, such as slowed emptying of your stomach
(gastroparesis) or problems digesting food?
❑ Do you take other diabetes medicines, such as insulin or
sulfonylureas?
❑ Do you have a history of diabetic retinopathy?
❑ Are you pregnant, plan to become pregnant, breastfeeding, or plan
to breastfeed? It is not known if Mounjaro will harm your
unborn baby or pass into your breast milk.
❑ Do you take any other prescription medicines or over-the-counter
drugs, vitamins, or herbal supplements?
How to take
- Read the Instructions for Use that come with
Mounjaro.
- Use Mounjaro exactly as your healthcare provider says.
- Mounjaro is injected under the skin (subcutaneously) of your
stomach (abdomen), thigh, or upper arm.
- Use Mounjaro 1 time each week, at any time of the
day.
- Do not mix insulin and Mounjaro together in the same
injection.
- You may give an injection of Mounjaro and insulin in the same
body area (such as your stomach area), but not right next to each
other.
- Change (rotate) your injection site with each weekly injection.
Do not use the same site for each injection.
- If you take too much Mounjaro, call your healthcare provider or
seek medical advice promptly.
Learn more
Mounjaro is a prescription medicine. For more information, call
1-833-807-MJRO (833-807-6576) [or go to
www.mounjaro.com].
This summary provides basic information about Mounjaro but does
not include all information known about this medicine. Read the
information that comes with your prescription each time your
prescription is filled. This information does not take the place of
talking with your healthcare provider. Be sure to talk to your
healthcare provider about Mounjaro and how to take it. Your
healthcare provider is the best person to help you decide if
Mounjaro is right for you.
TR CON CBS 14SEP2022
Mounjaro® and its delivery device base are
registered trademarks owned or licensed by Eli Lilly and Company,
its subsidiaries, or affiliates.
About Lilly
Lilly is a medicine company turning
science into healing to make life better for people around the
world. We've been pioneering life-changing discoveries for nearly
150 years, and today our medicines help more than 51 million people
across the globe. Harnessing the power of biotechnology, chemistry
and genetic medicine, our scientists are urgently advancing new
discoveries to solve some of the world's most significant health
challenges: redefining diabetes care; treating obesity and
curtailing its most devastating long-term effects; advancing the
fight against Alzheimer's disease; providing solutions to some of
the most debilitating immune system disorders; and transforming the
most difficult-to-treat cancers into manageable diseases. With each
step toward a healthier world, we're motivated by one thing: making
life better for millions more people. That includes delivering
innovative clinical trials that reflect the diversity of our world
and working to ensure our medicines are accessible and affordable.
To learn more, visit Lilly.com and Lilly.com/news, or follow us on
Facebook, Instagram and LinkedIn. P-LLY
i Not controlled for type 1 error.
ii The efficacy estimand represents efficacy had
all patients remained on randomized treatment for the entire
planned treatment duration (up to 176 weeks).
iii The treatment-regimen estimand represents
efficacy regardless of adherence to randomized treatment.
Cautionary Statement Regarding Forward-Looking
Statements
This press release contains forward-looking
statements (as that term is defined in the Private Securities
Litigation Reform Act of 1995), including statements about
tirzepatide injection for the treatment of adults with type 2
diabetes, tirzepatide as a potential long-term therapy for adults
with pre-diabetes and obesity or overweight and the timeline for
future presentations and other milestones relating to tirzepatide
and its clinical trials, and reflects Lilly's current belief and
expectations. However, as with any pharmaceutical product, there
are substantial risks and uncertainties in the process of research
development and commercialization. Among other things, there can be
no guarantee that planned or ongoing studies will be completed as
planned, that future study results will be consistent with the
results to date, that tirzepatide will receive additional
regulatory approvals, or that tirzepatide will be commercially
successful. For further discussion of these and other risks and
uncertainties, see Lilly's most recent Form 10-K and Form 10-Q
filings with the United States Securities and Exchange Commission.
Except as required by law, Lilly undertakes no duty to update
forward-looking statements to reflect events after the date of this
release.
Refer to:
|
Courtney C Kasinger:
ckasinger@lilly.com, 317-501-7056 (Media)
|
|
Joe Fletcher:
jfletcher@lilly.com, 317-296-2884 (Investors)
|
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