Lilly’s Trulicity Approved in Canada to Reduce Risk of Non-Fatal Stroke in Adults with Type 2 Diabetes and Cardiovascular Risk

September 27, 2020 News /Bio ValleyBIOON/ --Eli Lilly(Eli Lilly) recently announced that Health Canada has approved the antidiabetic drug Trulicity (dulaglutide), a once-weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA), as an adjunct to diet, exercise, and standard care for patients with type 2 diabetes who have cardiovascular (CV) disease or multiple cardiovascular risk factors.DiabetesIn adult patients, it reduces the risk of non-fatal stroke. This approval makes Trulicity the first and only GLP-1 RA approved to provide cardiovascular (CV) benefits for patients with CV disease or multiple CV risk factors.

In terms of U.S. regulatory affairs, Trulicity received approval in February this yearFDAApproved for use in patients with type 2 diabetes who have cardiovascular disease or multiple cardiovascular risk factorsDiabetesIn adult patients, it reduces the risk of major adverse cardiovascular events (MACE). Notably, this approval makes Trulicity the first and only medication approved to reduce the risk of MACE in both primary and secondary prevention populations with type 2DiabetesMedication.

This new indication reflects the differentiated patient population of the REWIND cardiovascular outcomes trial for Trulicity. Although all participants had cardiovascular risk factors, the study primarily consisted of patients without established cardiovascular disease. The results showed that, compared with placebo, Trulicity reduced major adverse cardiovascular events (MACE 3: non-fatalMyocardial InfarctionThe risk of the composite endpoint of [myocardial infarction], non-fatal stroke, and cardiovascular death was significantly reduced by 12%. Furthermore, Trulicity demonstrated a consistent reduction in MACE risk across major demographic and disease subgroups (including those with or without cardiovascular disease), with sustained cardiovascular risk reduction throughout the study. The safety profile of Trulicity was consistent with that of GLP-1 receptor agonists, and the most common adverse events leading to discontinuation of Trulicity were gastrointestinal events.

Based on the results of the REWIND study, Trulicity is the first type 2 diabetes medication to significantly reduce MACE events in a study where the majority of enrolled patients had cardiovascular (CV) risk factors but no established CV disease.DiabetesMedication. Patients with diabetes inherently have a higher cardiovascular (CV) risk. The study data are highly significant, confirming the therapeutic benefits of Trulicity in a broad population of patients with type 2 diabetes.

Hertzel Gerstein, Chair of the REWIND study, Professor of Medicine at McMaster University, and Deputy Director of the Population Health Research Institute at Hamilton Health Sciences, stated: “The REWIND study demonstrated that Trulicity reduces major cardiovascular events, including non-fatal stroke, in patients with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors. Trulicity reduces non-fatal stroke in these patients.”Strokenew indications for risk, will provide clinicians with an important tool for treating type 2 diabetes.”

Eli LillyDr. Doron Sagman, Vice President of Research and Development and Medical Affairs at the Canadian company, stated: “GLP-1 RA therapies represent a significant advance in the treatment of type 2 diabetes. Combined with Trulicity’s proven efficacy and reduction in non-fatal strokeStrokenew high-risk indications, this drug represents a significant milestone in the management of diabetes and cardiovascular disease.”

Trulicity is a glucagon-like peptide-1 (GLP-1) receptor agonist (RA) administered via subcutaneous injection once weekly. It is indicated, in conjunction with diet and exercise, to improve glycemic control in adults with type 2 diabetes. GLP-1 RAs are a highly prominent class of antidiabetic agents. GLP-1 RAs are not insulin; rather, they are a novel class of insulin secretagogues. Their mechanism of action mimics that of the endogenous hormone GLP-1, stimulating the body’s own insulin secretion in response to food intake. They offer potent glucose-lowering efficacy and a lower risk of hypoglycemia, while also possessingWeight LossEfficacy and the advantage of conferring cardiovascular benefits.

Since its U.S. launch in 2014, Trulicity has become the most prescribed GLP-1 receptor agonist (GLP-1RA). In addition to its proven glycemic efficacy and user-friendly delivery device, Trulicity is now also indicated to help reduce the risk of cardiovascular events in patients with type 2 diabetes. According to forecasts by the pharmaceutical market research firm EvaluatePharma, Trulicity’s sales will reach $7.13 billion in 2024, making it the best-selling antidiabetic medication worldwide.

REWIND was a multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the effect of once-weekly Trulicity 1.5 mg versus placebo (both added to standard care) on cardiovascular (CV) events in adult patients with type 2 diabetes. The primary CV endpoint was major adverse cardiovascular events (MACE-3: including cardiovascular death, non-fatalMyocardial Infarction, non-fatal stroke) as the time to first occurrence. Secondary endpoints included each component of the primary cardiovascular (CV) composite endpoint, a composite clinical microvascular outcome comprising retinopathy or nephropathy, hospitalization for unstable angina, heart failure requiring hospitalization, urgent visits for heart failure, and all-cause mortality. The study enrolled 9,901 patients with type 2 diabetes from 24 countries worldwide. These patients had a mean disease duration of 10.5 years and a mean baseline HbA1c of 7.2%. Although all patients had cardiovascular risk factors, only 31% had established CV disease at baseline.

The results demonstrated that the study met its primary efficacy endpoint: in the overall study population, Trulicity significantly reduced the risk of MACE events compared with placebo (HR=0.88, 95% CI: 0.79–0.99). This treatment effect was consistent across all subgroups: (1) patients with cardiovascular (CV) disease (HR=0.87, 95% CI: 0.74–1.02) and those without CV disease (HR=0.87, 95% CI: 0.74–1.02); (2) baseline A1C ≥7.2% (HR=0.86, 95% CI: 0.74–1.00) and baseline A1C <7.2% (HR=0.90, 95% CI: 0.76–1.06); and (3) females (HR=0.85, 95% CI: 0.71–1.02) and males (HR=0.90, 95% CI: 0.79–1.04).

All components of MACE-3 demonstrated a reduction in risk, including cardiovascular death (HR=0.91, 95% CI: 0.78–1.06), non-fatal myocardial infarction (HR=0.96, 95% CI: 0.79–1.16), and non-fatalStroke(HR=0.76, 95% CI: 0.61-0.95). Furthermore, Trulicity further demonstrated a reduction in composite microvascular outcomes (HR=0.87, 95% CI: 0.79-0.95). Analysis of renal outcomes indicated that long-term use of Trulicity was associated with a reduced progression of kidney disease in patients with type 2 diabetes.

In addition to long-term follow-up assessments of cardiovascular outcomes, the REWIND study provided further evidence of the efficacy of Trulicity in the treatment of diabetes. Compared with placebo, Trulicity reduced A1C from a median baseline of 7.2% in the overall study population (A1C: −0.46% [Trulicity] vs. +0.16% [placebo]; body weight: −2.95 kg [Trulicity] vs. −1.49 kg [placebo]). The safety profile of Trulicity in this study was consistent with that of the GLP-1 receptor agonist class. The most common adverse events leading to discontinuation of Trulicity were gastrointestinal events.

The REWIND study is distinctly different from other cardiovascular (CV) outcome trials due to the lower proportion of enrolled patients with pre-existing CV disease, which enabled the evaluation of the CV effects of Trulicity in a broader population of patients with type 2 diabetes. Importantly, the REWIND study had a median follow-up duration of 5.4 years, exceeding five years and representing the longest follow-up period among all GLP-1 receptor agonist (GLP-1RA) CV outcome trials. Furthermore, this study featured the lowest baseline HbA1c (7.2%) and a more balanced ratio of female (46.3%) to male (53.7%) participants among all diabetes CV studies conducted to date. This patient population is more representative of individuals with type 2 diabetes commonly encountered in clinical practice. In contrast, other CV outcome trials included higher proportions of patients with elevated baseline HbA1c levels and a greater prevalence of established CV disease at baseline.

REWIND was an ambitious study that evaluated whether Trulicity could protect patients without cardiovascular (CV) disease from experiencing their first CV event, and whether it could prevent subsequent CV events in patients with existing CV disease. The results clearly demonstrated that Trulicity effectively reduced the risk of major adverse cardiovascular events (MACE) across a broad population of individuals with type 2 diabetes, providing compelling data. (Bioon.com)

Original Source: Trulicity® (dulaglutide) is now indicated as an adjunct to diet, exercise, and standard of care therapy to reduce the risk of non-fatal stroke in adults with type 2 diabetes mellitus who have multiple cardiovascular risk factors or established cardiovascu