Lilly’s SURPASS-2 results published in The New England Journal of Medicine show tirzepatide achieved superior A1C and body weight reductions compared to injectable semaglutide in adults with type 2 diabetes

All three doses of tirzepatide achieved superior A1C and weight reductions compared to semaglutide in data simultaneously presented at the American Diabetes Association’s ® 81 st Scientific Sessions ®

TORONTO, ON, June 28, 2021 – Tirzepatide led to superior A1C 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 on June 25 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, June 29, showed that all three tirzepatide doses achieved greater A1C and weight reductions compared to semaglutide.

Additionally, a prespecified exploratory composite endpoint was evaluated, which comprised of participants who achieved an A1C level less than or equal to 6.5 per cent and weight loss of 10 per cent or greater, while not experiencing hypoglycemia less than 3 mmol/L or severe hypoglycemia. Across the three doses of tirzepatide, 32 per cent (5 mg), 51 per cent (10 mg) and 60 per cent (15 mg) of participants achieved this composite endpoint compared to 22 per cent of participants taking semaglutide 1 mg. 1,2

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.

“Tirzepatide delivered superior A1C and weight reductions compared to semaglutide. The 15 mg dose of tirzepatide achieved less than or equal to 6.5 per cent combined with a weight loss of 10 per cent or greater, in 60 per cent of patients, without clinically significant hypoglycemia. The ability to achieve these challenging treatment goals is highly meaningful to clinicians and people living with type 2 diabetes,” said Dr. Alice Cheng, MD, FRCPC, Endocrinologist, Trillium Health Partners & Unity Health Toronto, Associate Professor, University of Toronto. “These are impressive findings, and if approved, tirzepatide will be an exciting and promising new treatment option for Canadians with type 2 diabetes.”

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. Semaglutide is a GLP-1 receptor agonist, and 1 mg is the highest dose of semaglutide that is approved by Health Canada for the treatment of 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 A1C of 8.28 per cent and a baseline weight of 93.7 kg.

For both estimands i, all three doses of tirzepatide demonstrated superior A1C and body weight reductions compared to semaglutide 1 mg. Specifically, results in the efficacy ii showed:

  • A1C reduction: -2.09% (5 mg), -2.37% (10 mg), -2.46% (15 mg), -1.86% (semaglutide)

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

  • Percentage of participants achieving A1C <7%: 85% (5 mg), 89% (10 mg), 92% (15 mg), 81% (semaglutide)

  • Percentage of participants achieving A1C <5.7%: 29% (5 mg, not controlled for type 1 error), 45% (10 mg), 51% (15 mg), 20% (semaglutide)

The treatment-regimen estimand iii results were consistent with topline results and showed that tirzepatide led to A1C reductions of -2.01% (5 mg, p=0.018), -2.24% (10 mg, p<0.001) and -2.30% (15 mg, p<0.001) compared to semaglutide at -1.86%, and weight reductions of -7.6 kg (5 mg), -9.3 kg (10 mg) and -11.2 kg (15mg) compared to semaglutide at -5.7 kg, all p<0.001.

For the treatment-regimen estimand[sup]iii[/sup], all three doses of tirzepatide delivered superior A1C and body weight reductions compared to semaglutide. Greater percentages of participants achieved an A1C of less than 7 per cent across all three doses compared to semaglutide, with statistical significance met for 10 mg and 15 mg, but not for 5 mg. Specifically:

  • A1C reduction: -2.01% (5 mg), -2.24% (10 mg), -2.30% (15 mg), -1.86% (semaglutide)

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

  • Percentage of participants achieving A1C <7%: 82% (5 mg), 86% (10 mg), 86% (15 mg), 79% (semaglutide)

  • Percentage of participants achieving A1C <5.7%: 27% (5 mg), 40% (10 mg), 46% (15 mg), 19% (semaglutide)

Hypoglycemia less than 3 mmol/L was reported in 0.6 per cent (5 mg), 0.2 per cent (10 mg) and 1.7 per cent (15 mg) of participants in the tirzepatide arms and in 0.4 per cent of participants in the semaglutide arm.

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

The most commonly reported adverse events across all treatment arms were gastrointestinal and mostly mild- to moderate, including nausea (17.4 per cent [5 mg], 19.2 per cent [10 mg], 22.1 per cent [15 mg], 17.9 per cent [semaglutide]), diarrhea (13.2 per cent [5 mg], 16.4 per cent [10 mg], 13.8 per cent [15 mg], 11.5 per cent [semaglutide]) and vomiting (5.7 per cent [5 mg], 8.5 per cent [10 mg], 9.8 per cent [15 mg], 8.3 per cent [semaglutide]). Treatment discontinuation rates due to adverse events were 6.0 per cent (5 mg), 8.5 per cent (10 mg), 8.5 per cent (15 mg) and 4.1 per cent (semaglutide).

“These data position tirzepatide as an innovative, new treatment option that could change the treatment landscape for type 2 diabetes,” said Dr. Doron Sagman, vice president, R&D and Medical Affairs, Eli Lilly Canada. “The exceptional results from this study suggest that tirzepatide could help people with type 2 diabetes and their healthcare providers achieve their A1C and weight treatment goals.”

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 in adults with type 2 diabetes inadequately controlled with ≥1500 mg/day metformin alone. The trial randomized 1,879 study participants across Canada, the U.S., Argentina, Australia, Brazil, 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 A1C reductions from baseline compared to semaglutide after 40 weeks in people with type 2 diabetes. Key secondary objectives included non-inferior A1C reductions from baseline for tirzepatide 5 mg; superior A1C and body weight reductions from baseline and greater percentages of participants achieving an A1C less than 7 per cent across all three tirzepatide doses; and greater percentages of participants achieving an A1C less than 5.7 per cent for tirzepatide 10 mg and 15 mg compared to semaglutide. Additional secondary endpoints not controlled for type 1 error included percentage of participants achieving an A1C less than 5.7 per cent for tirzepatide 5 mg compared to semaglutide. Study participants had a mean A1C between 7 per cent and 10.5 per cent and a BMI greater than or equal to 25 kg/m 2. 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

Approximately 11 million Canadians are living with diabetes or prediabetes. Roughly 90 per cent of people living with diabetes have type 2 diabetes 3.

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 Canada

Eli Lilly and Company 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 Colonel Eli Lilly, who was committed to creating high quality medicines that meet people’s needs, and today we remain true to that mission in all our work. Lilly employees work to discover and bring life-changing medicines to people who need them, improve the understanding and management of disease, and contribute to our communities through philanthropy and volunteerism.

Eli Lilly Canada was established in 1938, the result of a research collaboration with scientists at the University of Toronto, which eventually produced the world’s first commercially available insulin. Our work focuses on oncology, diabetes, autoimmunity, neurodegeneration, and pain. To learn more about Lilly Canada, please visit us at www.lilly.ca.

For our perspective on issues in healthcare and innovation, follow us on twitter @LillyPadCA and @LillyMedicalCA.

This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about tirzepatide as a potential treatment for patients with diabetes and reflects Lilly's current beliefs. However, as with any such undertakings, there are substantial risks and uncertainties in the process of drug development and commercialization. Among other things, there can be no guarantee that future study results will be consistent with the results to date, that tirzepatide will prove to be a safe and effective treatment for diabetes, that tirzepatide will receive regulatory approvals or authorizations, or be commercially successful. For a further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, please see Lilly's most recent Forms 10-K and 10-Q filed with the U.S. Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.

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References:

  1. Frias, J.P, et. al. (2021). Tirzepatide vs. Semaglutide Once Weekly for Patients with Type 2 Diabetes. The New England Journal of Medicine, 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 81st Scientific Sessions; June 25-29.

  3. Diabetes Canada. What is diabetes. 2021. Available at: https://www.diabetes.ca/about-diabetes/what-is-diabetes

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 hyperglycemia.

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