The drug dulaglutide reduced cardiovascular events and kidney problems in people with Type 2 diabetes

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A clinical trial that followed more than 9,900 people in 24 countries has found that the drug dulaglutide reduced cardiovascular events and kidney problems in middle-aged and older people with Type 2 diabetes.

During more than five years of follow-up, cardiovascular events like heart attacks and strokes were reduced by 12% in people taking dulaglutide compared to people taking a placebo.

This effect was seen in both men and women with or without previous cardiovascular disease.

In addition, during the same period, the drug reduced the development of kidney disease by 15%.

The trial was led by the Population Health Research Institute (PHRI) of McMaster University and Hamilton Health Sciences.

Two papers describing the cardiovascular and kidney results of the trial were published today in the journal The Lancet from the study called the Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial.

“Compared to others, people with diabetes have twice the rate of cardiovascular events like heart attacks and strokes, and up to 40% of people with diabetes develop kidney disease,” said Hertzel C. Gerstein, principal investigator for the study, professor of medicine at McMaster and deputy director of the PHRI.

Dr. Hertzel Gerstein talks about the REWIND trial. Credit: Hamilton Health Sciences.
“The REWIND trial shows that dulaglutide can safely reduce these events while improving diabetes control and modestly lowering weight and blood pressure in middle-aged people with Type 2 diabetes.”

Nearly one in five people over the age of 60 have diabetes and most have Type 2 diabetes.

Altogether, nearly ten per cent of adults are living with diabetes, including 425 million people worldwide; 100 million in the U.S., and three million people in Canada.

Dulaglutide is a glucagon-like peptide-1 receptor agonist that is injected once per week.

It is approved for glucose lowering and works by helping the pancreas release the right amount of insulin when blood sugar levels are high, slowing the emptying of the stomach after a meal, and reducing appetite and weight.

Risultati immagini per Dulaglutide

Gerstein pointed out the trial participants were very similar to the sorts of people with diabetes who are seen in medical practice. Participants were followed for a median of 5.4 years, much longer than previous trials, and more than 46 per cent of participants were women. Less than a third of participants had previous cardiovascular disease.

The drug was well tolerated, modestly reduced weight, low-density lipoprotein (LDL) cholesterol and blood pressure, and modestly increased heart rate.

Gastrointestinal side effects including constipation or diarrhea were reported more frequently in participants taking dulaglutide (47%) compared to placebo (34%).


Type 2 diabetes (T2D) is the leading cause of chronic kidney disease (CKD) worldwide.12

Patients with T2D and low kidney function have limited treatment options because medications that are cleared by the kidney (e.g. biguanides and some sulphonylureas) often require dosage adjustments, and many are contraindicated.123 

In addition, patients with T2D and CKD are at a higher risk of hypoglycaemia compared with patients with T2D because of decreased gluconeogenesis by the kidney as well as decreased clearance of insulin and of some other diabetes medications.4 

Diabetes medications not cleared by the kidney and associated with a low risk of hypoglycaemia would represent a clinically significant advance for patients with T2D and CKD.

Dulaglutide is a once‐weekly glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA).

In phase II and phase III registration studies, dulaglutide was found to have superior glycaemic efficacy compared with placebo, exenatide, insulin glargine, metformin and sitagliptin.5 

Because of its large molecular size, dulaglutide is not cleared by the kidney,5 but is presumably catabolized by proteolytic degradation.

In a phase I study, no clinically relevant change in the pharmacokinetics of dulaglutide was observed in participants with low kidney function.5

The primary objective of the present study was to evaluate the effects of dulaglutide on kidney function and safety in patients with T2D.

This study presents integrated data from 9 clinical trials (ClinicalTrials.gov): NCT00630825NCT00791479NCT01001104NCT01149421NCT01064687NCT00734474NCT01075282NCT01191268; and NCT01126580.


Journal information: The Lancet
Provided by McMaster University

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