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, IN, USA I August 20, 2024 I 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.
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.
- 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.
SOURCE: Eli Lilly
Post Views: 1,860
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, IN, USA I August 20, 2024 I 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.
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.
- 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.
SOURCE: Eli Lilly
Post Views: 1,860
