Trulicity ® (dulaglutide) injection

0.75 mg/0.5 mL, 1.5 mg/0.5 mL, 3mg/0.5mL, 4.5mg/0.5mL

This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.

Does Trulicity® (dulaglutide) have cardiovascular benefits?

The REWIND study showed that Trulicity (dulaglutide) 1.5 mg significantly reduced MACE-3 when compared to placebo.

Detailed Information

Dulaglutide is a GLP-1 RA indicated

  • as an adjunct to diet and exercise to improve glycemic control in adults with T2DM, and

  • to reduce the risk of MACE in adults with T2DM who have established CV disease or multiple CV risk factors.1

The REWIND study was an event-driven, randomized, double-blind, phase 3 CV outcomes study of dulaglutide.2

The study evaluated the effect on MACE-3 and other serious outcomes with once-weekly dulaglutide 1.5 mg treatment compared with placebo when added to standard of care in participants 50 years of age and older with T2DM and established CV disease and/or risk factors.2

The REWIND trial was sponsored by Eli Lilly and Company, site management and data collection were conducted by ICON Clinical Research, scientific leadership was provided by an international steering committee coordinated by the Population Health Research Institute in Hamilton, Canada, and data analysis was conducted by the Population Health Research Institute.2

Key Inclusion/Exclusion Criteria

Eligible patients had

  • newly diagnosed or established T2DM

  • an HbA1c value of 9.5% or lower, and

  • vascular diseases or CV risk factors depending on their age (Table 1).3

Table 1. Age-Specific Inclusion Criteria for REWIND Trial2

If the participant's age is... 

They had to have... 

50-54 y

established CVD. 

55-59 y

established CVD or evidence of other subclinical CVD. 

60 y or older

established CVD, evidence of other subclinical CVD, or at least 2 other CV risk factors.

Abbreviations: CV = cardiovascular; CVD = cardiovascular disease; REWIND = Researching cardiovascular Events with a Weekly INcretin in Diabetes.

Patients were excluded if they had

  • liver disease

  • a history of pancreatitis

  • gastric emptying abnormalities

  • an eGFR of less than 15 mL/min/1.73m2 or on dialysis

  • a coronary or cerebrovascular event in the last 2 months or plans to revascularize, or

  • history of medullary C-cell hyperplasia or medullary thyroid cancer.2,3

Outcome Measures

The primary outcome was the first occurrence of the composite MACE-3 endpoint which included

  • death due to CV causes,

  • nonfatal MI, or

  • nonfatal stroke.2,3

An external adjudication committee that was blinded to treatment allocation was to adjudicate all deaths, CV, pancreatic, and thyroid events.2,3

Study follow-up continued until 1200 adjudicated events of primary outcomes were confirmed.2,3

Baseline Characteristics

A total of 9901 patients in 24 countries were randomized.2,4

Results

Dulaglutide 1.5 mg significantly reduced MACE-3 when compared to placebo (HR=0.88 [95% CI 0.79, 0.99]; p = .026), demonstrating a decrease in CV events and showing safety in a population that included a majority of participants without established CV disease.3

Each component of MACE-3 is described in Table 2

Table 2. Effects of Dulaglutide 1.5 mg on Each Component of the Primary Outcome of MACE-33

CV Parameter

HR (95% CI)

Nonfatal MI

0.96 (0.79, 1.16)

Nonfatal stroke

0.76 (0.61, 0.95)

CV death

0.91 (0.78, 1.06)

Abbreviations: CV = cardiovascular; HR = hazard ratio; MACE-3 = major adverse cardiovascular events (death due to cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke); MI = myocardial infarction.

The median follow-up time in REWIND was 5.4 years. The safety profile of dulaglutide in REWIND was generally consistent with the GLP-1 RA class. Dulaglutide did not significantly increase any of the prespecified adverse events of special interest, including first study drug discontinuation, serious gastrointestinal events, severe hypoglycemia, cancers, immune reactions, or pancreatitis.3

Enclosed Prescribing Information

TRULICITY® (dulaglutide) injection, for subcutaneous use, Lilly

References

The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).

1. Trulicity [package insert]. Indianapolis, IN: Eli Lilly and Company; 2020.

2. Gerstein HC, Colhoun HM, Dagenais GR, et al. REWIND Trial Investigators. Design and baseline characteristics of participants in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial on the cardiovascular effects of dulaglutide. Diabetes Obes Metab. 2018;20(1):42-49. https://doi.org/10.1111/dom.13028

3. Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. The Lancet. 2019;394(10193):121-130. https://doi.org/10.1016/S0140-6736(19)31149-3

4. Researching cardiovascular events with a weekly incretin in diabetes (REWIND). ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/NCT01394952. Updated January 16, 2018. Accessed July 2, 2018.

Glossary

CV = cardiovascular

eGFR = estimated glomerular filtration rate

GLP-1 RA = glucagon-like peptide-1 receptor agonist

HbA1c = glycated hemoglobin

HR = hazard ratio

MACE = major adverse cardiovascular event

MACE-3 = major adverse cardiovascular events (death due to cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke)

MI = myocardial infarction

REWIND = Researching cardiovascular Events with a Weekly INcretin in Diabetes

T2DM = type 2 diabetes mellitus

Date of Last Review: July 13, 2020

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