Lilly's tirzepatide significantly reduced A1C and body weight in people with type 2 diabetes

More than half of participants taking the highest dose achieved normal A1C levels, a key secondary endpoint in first phase 3 trial of SURPASS program

Participants in this monotherapy study had relatively recently diagnosed diabetes, with a mean duration of 4.7 years

TORONTO, Dec. 14, 2020 /CNW/ - Tirzepatide led to superior A1C and body weight reductions from baseline in adults with type 2 diabetes after 40 weeks of treatment in topline results from Eli Lilly and Company's SURPASS-1 monotherapy clinical trial evaluating the efficacy and safety of tirzepatide compared to placebo. Using the efficacy estimandⁱ, the highest dose of tirzepatide led to an A1C reduction of 2.07 per cent and reduced body weight by 9.5 kg (11.0 per cent). More than half (51.7 per cent) of participants in this arm achieved an A1C less than 5.7 per cent – the level seen in people without diabetes.

The overall safety profile of tirzepatide was similar to the well-established GLP-1 receptor agonist class, with gastrointestinal side effects being the most commonly reported adverse events. Treatment discontinuation rates due to adverse events were less than 7 per cent in each tirzepatide treatment arm.

Tirzepatide is a novel investigational 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 molecule, representing a new class of medicines being studied for the treatment of type 2 diabetes. The primary and key secondary endpoints of SURPASS-1, the first phase 3 trial of the comprehensive SURPASS program, included superior A1C and mean body weight reductions compared to placebo. Study participants, 54.2 per cent of whom were treatment-naïve, had a relatively short mean duration of diabetes of 4.7 years, a baseline A1C of 7.9 per cent and a baseline weight of 85.9 kg.

"These phase 3 data for tirzepatide are exciting and build upon the phase 2 data released in 2018, with exceptional A1C and weight reductions seen in people with type 2 diabetes," says Dr. Sue Pedersen, endocrinologist  and diabetes/obesity clinical trial investigator at C-ENDO Diabetes & Endocrinology Clinic, in Calgary, AB. "When looking at A1C targets from the study, nearly 90 per cent of participants in the tirzepatide arms of the trial met the A1C goal of less than 7 per cent, and more than half of participants taking the highest dose of tirzepatide achieved an A1C of less than 5.7 per cent, which is considered normal by US criteria - a remarkable result that has not been seen before in glucose-lowering agents."

Treatment differences for two estimands – efficacy and treatment-regimenⁱⁱ – were evaluated for the three tirzepatide doses (5 mg, 10 mg, and 15 mg) compared to placebo. Across both estimands, all three tirzepatide doses reached statistical significance in A1C and body weight reductions from baseline and in the percentage of participants who achieved an A1C of less than 7 per cent (the American Diabetes Association's recommended target for people with diabetes) or less than 5.7 per cent.

Efficacy Estimand Results^iii
	Tirzepatide 5 mg	Tirzepatide 10 mg	Tirzepatide 15 mg	Placebo
A1C reduction from baseline of 7.9%	-1.87%	-1.89%	-2.07%	+0.04%
Placebo-adjusted A1C reduction	-1.91%	-1.93%	-2.11%	N/A
Weight reduction from baseline of 85.9 kg	-7.0 kg (-7.9%)	-7.8 kg (-9.3%)	-9.5 kg (-11.0%)	-0.7 kg (-0.9%)
Placebo-adjusted weight reduction	-6.3 kg	-7.1 kg	-8.8 kg	N/A
Percent of participants achieving A1C <7%	86.8%	91.5%	87.9%	19.6%
Percent of participants achieving A1C <5.7%	33.9%	30.5%	51.7%	0.9%

In the treatment-regimen estimand, each of the tirzepatide doses led to statistically significant A1C and body weight reductions:

• A1C reduction: -1.75% (5 mg), -1.71% (10 mg), -1.69% (15 mg), -0.09% (placebo)
• Weight reduction: -6.3 kg (5 mg), -7.0 kg (10 mg), -7.8 kg (15 mg), -1.0 kg (placebo)
• Percentage of participants achieving A1C <7%: 81.8% (5 mg), 84.5% (10 mg), 78.3% (15 mg), 23.0% (placebo)
• Percentage of participants achieving A1C <5.7%: 30.9% (5 mg), 26.8% (10 mg), 38.4% (15 mg), 1.4% (placebo)

No events of severe hypoglycemia or hypoglycemia less than 54 mg/dL were observed in the tirzepatide treatment arms.

The most commonly reported adverse events were gastrointestinal-related and mild to moderate in severity, usually occurring during the dose escalation period. For study participants treated with tirzepatide (5 mg, 10 mg and 15 mg, respectively), nausea (11.6 per cent, 13.2 per cent, 18.2 per cent), diarrhea (11.6 per cent, 14.0 per cent, 11.6 per cent), vomiting (3.3 per cent, 2.5 per cent, 5.8 per cent) and constipation (5.8 per cent, 5.0 per cent, 6.6 per cent) were more frequently experienced compared to placebo (6.1 per cent [nausea], 7.8 per cent [diarrhea], 1.7 per cent [vomiting], 0.9 per cent [constipation]). The overall treatment discontinuation rates were 9.1 per cent (5 mg), 9.9 per cent (10 mg), 21.5 per cent (15 mg) and 14.8 per cent (placebo). The majority of the discontinuations in the 15 mg and placebo arms were due to reasons other than adverse events (such as concerns due to the coronavirus pandemic and family or work reasons).

"As a leader in diabetes care, we have a nearly 100-year heritage of innovating to advance care for people living with diabetes. Tirzepatide is the first dual GIP/GLP-1 receptor agonist to complete a phase 3 trial," said Mike Mason, president, Lilly Diabetes. "We are impressed by these initial results showing how tirzepatide performed in people with a relatively short duration of diabetes, and we look forward to seeing more results in people who are later in the course of diabetes in future studies from our robust SURPASS clinical trial program."

The complete SURPASS-1 study data have not yet been evaluated but will be presented at the American Diabetes Association's® 81^st Scientific Sessions® and published in a peer-reviewed publication in 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 receptor agonists. 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-1 and the SURPASS clinical trial program
SURPASS-1 (NCT03954834) is a 40-week, multi-centre, randomized, double-blind, parallel, placebo-controlled trial comparing the efficacy and safety of tirzepatide 5 mg, 10 mg and 15 mg as monotherapy to placebo in adults with type 2 diabetes inadequately controlled with diet and exercise alone. The trial randomized 478 study participants across the U.S., Mexico, India, and Japan in 1:1:1:1 ratio to receive either tirzepatide 5 mg, 10 mg or 15 mg or placebo. The objective of the study was to demonstrate that tirzepatide (5 mg, 10 mg or 15 mg) is superior in A1C reduction from baseline after 40 weeks in people with type 2 diabetes naïve to injectable therapy who haven't used any oral antidiabetic medicines within three months compared to placebo. Study participants had a mean A1C between 7 per cent and 9.5 per cent and a BMI greater than or equal to 23 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).

The SURPASS phase 3 global clinical development program for tirzepatide has enrolled more than 10,000 people with type 2 diabetes across eight clinical trials, five of which are global registration studies. The program began in late 2018 with results anticipated in late 2020 and 2021.

About Diabetes in Canada
Approximately 11 million Canadians live with diabetes or prediabetes. People with diabetes are over three times more likely to be hospitalized with cardiovascular disease and contribute to 30% of strokes and 40% of heart attacks. Diabetes can reduce lifespan by 5 to 15 years and complications are associated with premature death. It is estimated that the all-cause mortality rate among Canadians living with diabetes is twice as high as the all-cause mortality rate for people without diabetes.^iv

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 people 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 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

REFERENCES

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ⁱ Efficacy estimand represents efficacy prior to discontinuation of study drug or initiating rescue therapy for persistent severe hyperglycemia.

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

ⁱⁱⁱ All three tirzepatide doses led to statistically significant A1C and body weight reductions from baseline and also reached statistical significance in the percentage of participants who achieved an A1C of less than 7 percent or less than 5.7 percent. 

^iv www.diabetes.ca, Diabetes in Canada - Backgrounder, pg. 1, February 2020.

SOURCE Eli Lilly Canada Inc.

Media Contact: Ethan Pigott, [email protected], 416-770-5843

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