The Food and Drug Administration (FDA) has approved Trulicity (dulaglutide; Lilly) to reduce the risk of major adverse cardiovascular events (MACE; cardiovascular death, nonfatal myocardial infarction [MI], or nonfatal stroke) in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors.

The approval was based on data from the REWIND trial, a placebo-controlled, double-blind study that evaluated the effectiveness of dulaglutide in reducing MACE and other serious outcomes in patients with type 2 diabetes, when added to their antihyperglycemic regimen. Patients (N=9901) were randomized to receive dulaglutide 1.5mg or placebo; the most common background antidiabetic drugs used at baseline included metformin, sulfonylurea, and insulin. 

Patient demographics included a mean age of 66 years; 46% were female and the majority (76%) were White. The median baseline HbA1c was 7.2% and mean duration of type 2 diabetes was 10.5 years; mean BMI was 32.3 kg/m2. Of the 9713 patients whose eGFR was available, 50.5% of patients had mild renal impairment, 21.6% had moderate renal impairment, and 1.1% had severe renal impairment.

Among the study population, 31.5% had established cardiovascular disease, while 62.8% had multiple cardiovascular risk factors, but did not have established cardiovascular disease. At baseline, risk factors were managed with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (81.5%), beta blockers (45.6%), calcium channel blockers (34.4%), diuretics (46.5%), statin therapy (66.1%), antithrombotic agents (58.7%), and aspirin (51.7%).

The primary end point of the study was the time to the first occurrence of a composite 3-component MACE outcome, which included cardiovascular death, nonfatal MI, and nonfatal stroke; a Cox proportional hazard model was used to test for superiority. 

Results showed that treatment with dulaglutide led to a significant reduction in MACE risk compared with placebo (hazard ratio [HR] 0.88 (95% CI, 0.79-0.99). Based on a median follow-up duration of 5.4 years, 12% (n=594) of patients experienced an event (composite 3-component MACE outcome) compared with 13.4% (n=663) of patients in the placebo arm. 

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The safety profile of dulaglutide was found to be consistent with that observed with glucagon-like peptide-1 (GLP-1) receptor agonists (ie, nausea, diarrhea, vomiting, abdominal pain, decreased appetite). An increased risk of diabetic retinopathy complications was noted in the trial among patients with a history of diabetic retinopathy.

In addition to the cardiovascular indication, Trulicity is also approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. It is supplied in single-dose pens for subcutaneous injection.

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