Trulicity® (dulaglutide) significantly reduced major cardiovascular events for broad range of people with type 2 diabetes

REWIND data showed a consistent effect in people with and without established cardiovascular disease

TORONTO, June 10, 2019 /CNW/ - Detailed results from REWIND, the Trulicity^® (dulaglutide) cardiovascular outcome trial, showed a significant 12 per cent reduction in major cardiovascular events (MACE), a composite endpoint of non-fatal myocardial infarction (heart attack), non-fatal stroke or CV (cardiovascular) death. REWIND data showed a consistent MACE-3 effect in people with and without established CV disease. The CV risk reduction was sustained throughout the trial's duration.ⁱ  The highly anticipated data for Eli Lilly and Company's once-weekly Trulicity were presented during a symposium at the American Diabetes Association's^® 79th Scientific Sessions^® and simultaneously published in The Lancet.ⁱⁱ

REWIND is the longest cardiovascular outcome trial in the GLP-1 receptor agonist class (median 5.4 years) and consisted primarily of people without established CV disease. While all participants had CV risk factors, only 31 per cent of study participants had established CV disease. The study also had one of the lowest median baseline A1Cs of any diabetes CV outcome trial to date (7.2 per cent) and had a balanced ratio of women (46.3 per cent) to men (53.7 per cent). This patient population is more representative of people with type 2 diabetes typically seen in clinical practice.ⁱⁱⁱ

"The REWIND trial clearly demonstrated that in a population where the majority of participants had cardiovascular risk factors but no cardiovascular disease, dulaglutide provided significant impact beyond blood glucose control," said Hertzel Gerstein, M.D., MSc, FRCPC, Professor of Medicine and Deputy Director of the Population Health Institute at McMaster University and Hamilton Health Sciences, and REWIND study chair. "This is important new data for the Canadian diabetes community with dulaglutide as the first type 2 diabetes medicine to show a benefit in such a broad range of people."

REWIND compared the effect of Trulicity 1.5 mg to placebo, both in addition to standard of care, on the risk of MACE-3 in 9,901 adults with type 2 diabetes. The risk reduction shown by Trulicity for the overall study (HR=0.88, 95% CI: 0.79-0.99) was consistent across subgroups, including:^iv

• established cardiovascular disease: HR=0.87, 95% CI: 0.74-1.02;
• no established cardiovascular disease: HR=0.87, 95% CI: 0.74-1.02;
• baseline A1C greater than or equal to 7.2 per cent: HR=0.86, 95% CI: 0.74-1.00;
• baseline A1C less than 7.2 per cent: HR=0.90, 95% CI: 0.76-1.06;
• women: HR=0.85, 95% CI: 0.71-1.02; and
• men: HR=0.90, 95% CI: 0.79-1.04.

All three components contributed to the significant reduction Trulicity provided in MACE-3, including CV death (HR=0.91, 95% CI: 0.78-1.06), non-fatal heart attack (HR=0.96, 95% CI: 0.79-1.16) and non-fatal stroke (HR=0.76, 95% CI: 0.61-0.95). Trulicity further showed reductions in composite microvascular outcomes (HR=0.87, 95% CI: 0.79-0.95), characterized by fewer composite renal outcomes.^v Analysis of the renal outcomes suggests long-term Trulicity use was associated with reduced progression of renal disease in people with type 2 diabetes.^vi

In addition to the long-term follow-up assessing CV outcomes, REWIND provides additional evidence of Trulicity's efficacy in treating diabetes. Trulicity reduced A1C across the study from a median baseline of 7.2 per cent compared to placebo (A1C: -0.46 per cent [Trulicity], +0.16 per cent [placebo]; Weight: -2.95 kg [Trulicity], -1.49 kg [placebo]).^vii

Trulicity's safety profile was consistent with the GLP-1 receptor agonist class. The most common adverse events leading to the discontinuation of Trulicity were gastrointestinal events.^viii

"REWIND's detailed study results show a reduction of major CV adverse events in people with and without established CV disease," says Dr. Joanne Lorraine, Medical Director, Lilly Diabetes. "Trulicity has become an important treatment to help Canadians with diabetes reach their blood glucose goals in a once-weekly injection and this new data suggests that it can also provide some long-term cardiovascular benefits.

The REWIND results have been submitted to regulatory authorities in the U.S. and Europe for review.

About the REWIND Study
REWIND (Researching cardiovascular Events with a Weekly INcretin in Diabetes) was a multicentre, randomized, double-blind, placebo-controlled trial designed to assess the effect of Trulicity 1.5 mg, a weekly glucagon-like peptide 1 receptor agonist (GLP-1 RA), compared to placebo, both added to standard of care (according to local standard of care guidelines), on cardiovascular (CV) events in adults with type 2 diabetes. The primary CV outcome was the first occurrence of MACE (the composite of CV death or non-fatal myocardial infarction or non-fatal stroke). Secondary outcomes include each component of the primary composite CV outcome, a composite clinical microvascular outcome comprising retinal or renal disease, hospitalization for unstable angina, heart failure requiring hospitalization or an urgent heart failure visit, and all-cause mortality. The 9,901 participants from 24 countries had a mean duration of diabetes of 10.5 years and a median baseline A1C of 7.2 per cent. While all participants had CV risk factors, only 31 per cent of the study participants had established CV disease. Prior (or established) cardiovascular disease in REWIND was defined as prior myocardial infarction, prior ischemic stroke, prior unstable angina, prior revascularization (coronary, carotid, or peripheral), prior hospitalization for ischemia-related events (unstable angina or myocardial ischemia on imaging, or need for percutaneous coronary intervention), or prior documented myocardial ischemia.

The REWIND trial's international scope, high proportion of women, high proportion of people without established cardiovascular disease and inclusion of participants with a lower mean baseline A1C suggest that the findings will be directly relevant to the typical type 2 diabetes patient seen in general practice throughout the world.

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.

REFERENCES

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i	Gerstein HC, Colhoun HM, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. The Lancet. 2019. S0140-6736(19)31149-3. Retrieved from https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31149-3/fulltext.
ii	Gerstein HC, Colhoun HM, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. The Lancet. 2019. S0140-6736(19)31149-3. Retrieved from https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31149-3/fulltext.
iii	Boye KS, Riddle MC, Gerstein HC, et al. Generalizability of Glucagon-Like Peptide-1 Receptor Agonist Cardiovascular Outcome Trials to the Overall Type 2 Diabetes Population in the United States. Diabetes Obes Metab 2019.
iv	Gerstein HC, Colhoun HM, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. The Lancet. 2019. S0140-6736(19)31149-3. Retrieved from https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31149-3/fulltext.
v	Gerstein HC, Colhoun HM, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. The Lancet. 2019. S0140-6736(19)31149-3. Retrieved from https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31149-3/fulltext.
vi	Gerstein HC, Colhoun HM, et al. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. 2019. S0140-6736(19)31150. Retrieved from: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31150-X/fulltext.
vii	Gerstein HC, Colhoun HM, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. The Lancet. 2019. S0140-6736(19)31149-3. Retrieved from https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31149-3/fulltext.
viii	Gerstein HC, Colhoun HM, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. The Lancet. 2019. S0140-6736(19)31149-3. Retrieved from https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31149-3/fulltext.

SOURCE Eli Lilly Canada Inc.

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