Lilly’s SURPASS-2 results published in The New England Journal of Medicine show tirzepatide achieved superior HbA1C and body weight reductions compared to injectable semaglutide in adults with type 2 diabetes

Lilly’s SURPASS-2 results published in The New England Journal of Medicine show tirzepatide achieved superior HbA1C and body weight reductions compared to injectable semaglutide in adults with type 2 diabetes

All three doses of tirzepatide achieved superior HbA1C and weight reductions compared to semaglutide 1 mg in data simultaneously presented at the American Diabetes Association’s^® 81^st Scientific Sessions^®

BASINGSTOKE, 25^th June 2021 – Tirzepatide led to superior HbA1C and body weight reductions from baseline compared to injectable semaglutide 1 mg in 40-week results from Eli Lilly and Company’s (NYSE: LLY) SURPASS-2 clinical trial, which were simultaneously published today in The New England Journal of Medicine (NEJM)¹ and presented in a late breaking poster presentation during the American Diabetes Association’s^® (ADA) 81^st Scientific Sessions^®2. These results, which will also be featured during an ADA-sponsored symposium on Tuesday 29^th June, showed that all three tirzepatide doses achieved greater HbA1C and weight reductions compared to semaglutide 1 mg.

Additionally, a prespecified exploratory composite endpoint comprised of participants who achieved an HbA1C level less than or equal to 6.5 percent and weight loss of 10 percent or greater, while not experiencing hypoglycaemia less than 54 mg/dL (3 mmol/L) or severe hypoglycaemia, was evaluated. Across the three doses of tirzepatide, 32 percent (5 mg), 51 percent (10 mg) and 60 percent (15 mg) of participants achieved this composite endpoint compared to 22 percent of participants taking semaglutide 1 mg.^1,2

“In SURPASS-2, tirzepatide delivered clinically meaningful efficacy, and superior HbA1C and weight reductions compared to semaglutide 1 mg,” said Professor Melanie Davies, Professor of Diabetes Medicine at University of Leicester, NIHR Senior Investigator Emeritus and Principal Investigator of SURPASS-2. “Head-to-head data like these are very exciting, and underscore that, if approved, tirzepatide may be a promising new treatment option for people with type 2 diabetes here in the UK.”

The overall safety profile of tirzepatide was similar to the well-established glucagon-like peptide-1 (GLP-1) receptor agonist class. Across all treatment arms, the most commonly reported adverse events were gastrointestinal-related.

Tirzepatide is a novel investigational once-weekly dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist that integrates the actions of both incretins into a single molecule, representing a new class of medicines being studied for the treatment of type 2 diabetes. Injectable semaglutide 1 mg is a GLP-1 receptor agonist and the highest dose of injectable semaglutide approved by the EMA for the treatment of type 2 diabetes.

“These data suggest that tirzepatide has the potential to be a new treatment option to help people with type 2 diabetes better manage HbA1C and weight,” said Dr Kunal Gulati, Senior Medical Lead Diabetes, Lilly Northern Europe. “As a leader in diabetes care, Lilly is proud to be researching and developing solutions that can lead to meaningful HbA1C reductions and weight loss to help meet the needs of people with type 2 diabetes.”

SURPASS-2 was a 40-week, randomized, open-label trial comparing the efficacy and safety of tirzepatide to semaglutide as an add-on to metformin in adults with type 2 diabetes. The study randomized 1,879 participants, who had a mean duration of diabetes of 8.6 years, a baseline HbA1C of 8.28 percent and a baseline weight of 93.7 kg.

For both estimands^[i], all three doses of tirzepatide demonstrated superior HbA1C and body weight reductions compared to semaglutide 1 mg. Specifically, the efficacy estimand[ii] results showed:

·         HbA1C reduction: -2.09% (5 mg), -2.37% (10 mg), -2.46% (15 mg), -1.86% (semaglutide 1 mg)

·         Weight reduction: -7.8 kg (5 mg), -10.3 kg (10 mg), -12.4 kg (15 mg), -6.2 kg (semaglutide 1 mg)

·         Percent of participants achieving HbA1C <7%: 85% (5 mg), 89% (10 mg), 92% (15 mg), 81% (semaglutide 1 mg)

·         Percent of participants achieving HbA1C <5.7%: 29% (5 mg, not controlled for type 1 error), 45% (10 mg), 51% (15 mg), 20% (semaglutide 1 mg)

For the treatment-regimen estimand[iii], all three doses of tirzepatide delivered superior HbA1C and body weight reductions compared to semaglutide 1 mg. Greater percentages of participants achieved an HbA1C of less than 7 percent across all three doses compared to semaglutide 1 mg, with statistical significance met for 10 mg and 15 mg but not for 5 mg. Specifically:

·         HbA1C reduction: -2.01% (5 mg), -2.24% (10 mg), -2.30% (15 mg), -1.86% (semaglutide 1 mg)

·         Weight reduction: -7.6 kg (5 mg), -9.3 kg (10 mg), -11.2 kg (15 mg), -5.7 kg (semaglutide 1 mg)

·         Percent of participants achieving HbA1C <7%: 82% (5 mg), 86% (10 mg), 86% (15 mg), 79% (semaglutide 1 mg)

·         Percent of participants achieving HbA1C <5.7%: 27% (5 mg), 40% (10 mg), 46% (15 mg), 19% (semaglutide 1 mg)

Hypoglycaemia less than 3 mmol/L (clinically significant hypoglycaemia) was reported in 0.6 percent (5 mg), 0.2 percent (10 mg) and 1.7 percent (15 mg) of participants in the tirzepatide arms and in 0.4 percent of participants in the semaglutide 1 mg arm.

In an additional exploratory endpoint, all three doses of tirzepatide led to favourable changes from baseline in fasting lipids. Specifically, at the highest dose of tirzepatide (15 mg): triglycerides were reduced by 24.8 percent, very low-density lipoprotein (VLDL) cholesterol was reduced by 23.7 percent, and high-density lipoprotein (HDL) cholesterol was increased by 7.1 percent.²

The most commonly reported adverse events across all treatment arms were gastrointestinal-related and mostly mild-to-moderate, including nausea (17.4 percent [5 mg], 19.2 percent [10 mg], 22.1 percent [15 mg], 17.9 percent [semaglutide 1 mg]), diarrhoea (13.2 percent [5 mg], 16.4 percent [10 mg], 13.8 percent [15 mg], 11.5 percent [semaglutide 1 mg]) and vomiting (5.7 percent [5 mg], 8.5 percent [10 mg], 9.8 percent [15 mg], 8.3 percent [semaglutide 1 mg]). Treatment discontinuation rates due to adverse events were 5.1 percent (5 mg), 7.7 percent (10 mg), 7.9 percent (15 mg) and 3.8 percent (semaglutide 1 mg).

SURPASS-2 is the second of five global registration studies for tirzepatide in type 2 diabetes, all of which have been completed. Lilly intends to submit the full registration package to regulatory authorities by the end of 2021.

About tirzepatide

Tirzepatide is a once-weekly dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that integrates the actions of both incretins into a single novel molecule. GIP is a hormone that may complement the effects of GLP-1. In preclinical models, GIP has been shown to decrease food intake and increase energy expenditure therefore resulting in weight reductions, and when combined with a GLP-1 receptor agonist, may result in greater effects on glucose and body weight. Tirzepatide is in phase 3 development for blood glucose management in adults with type 2 diabetes and for chronic weight management. It is also being studied as a potential treatment for non-alcoholic steatohepatitis (NASH).

About SURPASS-2 and the SURPASS clinical trial program
SURPASS-2 (NCT03987919) is a 40-week, multi-center, randomized, parallel, open-label trial comparing the efficacy and safety of tirzepatide 5 mg, 10 mg and 15 mg to semaglutide 1 mg in adults with type 2 diabetes inadequately controlled with ≥1500 mg/day metformin alone. The trial randomized 1,879 study participants across the U.S., Argentina, Australia, Brazil, Canada, Israel, Mexico and the UK in a 1:1:1:1 ratio to receive either tirzepatide 5 mg, 10 mg or 15 mg or semaglutide 1 mg. The primary objective of SURPASS-2 was to demonstrate that the two higher doses of tirzepatide (10 mg and/or 15 mg) led to non-inferior HbA1C reductions from baseline compared to semaglutide 1 mg after 40 weeks in people with type 2 diabetes. Key secondary objectives included non-inferior HbA1C reductions from baseline for tirzepatide 5 mg; superior HbA1C and body weight reductions from baseline and greater percentages of participants achieving an HbA1C less than 7 percent across all three tirzepatide doses; and greater percentages of participants achieving an HbA1C less than 5.7 percent for tirzepatide 10 mg and 15 mg compared to semaglutide 1 mg. Additional secondary endpoints not controlled for type 1 error included percentage of participants achieving an HbA1C less than 5.7 percent for tirzepatide 5 mg compared to semaglutide 1 mg. Study participants had a mean HbA1C between 7 percent and 10.5 percent and a BMI greater than or equal to 25 kg/m². All participants in the tirzepatide treatment arms started the study at a dose of tirzepatide 2.5 mg once weekly and then increased the dose in a step-wise approach at four-week intervals to their final randomized maintenance dose of 5 mg (via a 2.5 mg step), 10 mg (via steps at 2.5 mg, 5 mg and 7.5 mg) or 15 mg (via steps at 2.5 mg, 5 mg, 7.5 mg, 10 mg and 12.5 mg). Participants in the semaglutide treatment arm started the study at a dose of semaglutide 0.25 mg once weekly for four weeks, then increased the dose to 0.5 mg for four weeks and then reached the final dose of 1 mg.

The SURPASS phase 3 global clinical development program for tirzepatide has enrolled more than 19,000 people with type 2 diabetes across 10 clinical trials, five of which are global registration studies.

About Diabetes

Nearly 4 million people in the UK³ and an estimated 463 million adults worldwide⁴ have diabetes. Type 2 diabetes is the most common type internationally, accounting for an estimated 90 percent of all diabetes cases in the UK alone⁵. Diabetes is a chronic disease that occurs when the body does not properly produce or use the hormone insulin.

About Lilly Diabetes

Lilly has been a global leader in diabetes care since 1923, when we introduced the world’s first commercial insulin. Today we are building upon this heritage by working to meet the diverse needs of people with diabetes and those who care for them. Through research, collaboration and quality manufacturing we strive to make life better for people affected by diabetes and related conditions. We work to deliver breakthrough outcomes through innovative solutions – from medicines and technologies to support programs and more.

About Eli Lilly and Company
Lilly is a global healthcare leader that unites caring with discovery to make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit lilly.co.uk.

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¹ Frias, J.P, et. al. (2021). Tirzepatide vs. Semaglutide Once Weekly for Patients with Type 2 Diabetes. The New England Journal of Medicine, http://www.nejm.org/doi/full/10.1056/NEJMoa2107519

² Frias, J.P. Efficacy and Safety of Tirzepatide vs. Semaglutide Once Weekly as Add-On Therapy to Metformin in Patients with Type 2 Diabetes. Abstract 84-LB. Presented virtually at the American Diabetes Association’s 81^st  Scientific Sessions; June 25-29.

³ Diabetes UK. Diabetes Prevalence 2019. Available from: https://www.diabetes.org.uk/professionals/position-statements-reports/statistics/diabetes-prevalence-2019. Last accessed: June 2021.

⁴ International Diabetes Federation. IDF Diabetes Atlas, 9^th edn. Brussels, Belgium: International Diabetes Federation, 2019. Available at: http://diabetesatlas.org.

⁵ Diabetes UK. Facts and Figures. Available from: https://www.diabetes.org.uk/professionals/position-statements-reports/statistics. Last accessed: June 2021.

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[i] Treatment differences for two estimands – efficacy and treatment-regimen – were evaluated for three tirzepatide doses (5 mg, 10 mg and 15 mg) compared to semaglutide 1 mg.

[ii] Efficacy estimand represents efficacy prior to discontinuation of study drug or initiating rescue therapy for persistent severe hyperglycaemia.

[iii] Treatment-regimen estimand represents the efficacy irrespective of adherence to the investigational medicine or introduction of rescue therapy for persistent severe hyperglycaemia.