FDA Approves Higher Doses for the Type 2 Diabetes Medication Dulaglutide

By Jessica Pyhtila, PharmD, BCGP, BCPS

The FDA recently approved two increased doses for dulaglutide, also known by its brand name Trulicity. Dulaglutide is a GLP1 agonist that is FDA-approved for glycemic control and primary or secondary cardiovascular risk reduction in Type 2 diabetes. The medication, which is administered subcutaneously by patients once weekly, was first approved in 2014. Like other GLP1 agonists, it works by activating the GLP1 receptor in the pancreas, leading to insulin-dependent glucose release. It additionally decreases glucagon secretion and slows gastric emptying.

The medication was previously approved only for the doses of 0.75 mg and 1.5 mg weekly. This approval has now been expanded to the higher doses of 3 mg and 4.5 mg weekly as well. The expanded approval was based on results from the AWARD-11 trial. This study was a phase 3, randomized, double-blind, parallel arm trial comparing the safety and efficacy of dulaglutide 1.5 mg weekly to 3 mg and 4.5 mg weekly. The study included 1,842 participants with a diagnosis of type 2 diabetes. Participants were initiated on the starting dulaglutide dose of 0.75 mg weekly and then were randomized to stepwise escalation to 1.5 mg, 3 mg or 4.5 mg weekly. The study showed that all doses showed statistically significant improvement compared to baseline values for A1c, body weight and fasting glucose. Further, at both 36 and 52 weeks of followup, the 3 mg and 4.5 mg doses showed significant improvement versus the 1.5 mg dose in terms of both glycemic control and body weight. On average, participants on dulaglutide 1.5 mg had an A1c reduction of 1.5% and lost 6.8 pounds. Dulaglutide 3.0 mg caused an average A1c reduction of 1.7% and an average weight loss of 8.8 pounds. The highest dose of dulaglutide, 4.5 mg, caused an average A1c reduction of 1.9% and an average weight loss of 10.4 pounds.

No new safety findings were discovered for the higher doses of dulaglutide in comparison to the lower doses. The higher doses of dulaglutide are expected to be available in the United States as of late September 2020.

Of note, like other GLP1 agonists, dulaglutide carries a Black Box Warning for medullary thyroid carcinoma, or MTC, and is contraindicated in those with Multiple Endocrine Neoplasia syndrome type 2 or a personal or family history of MTC.

Sources:

U.S. National Library of Medicine. (2020). “Trulicity, Dulaglutide Injection.” Retrieved from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=463050bd-2b1c-40f5-b3c3-0a04bb433309

Eli Lilly and Company. (2020). “FDA approves additional doses of Trulicity® (dulaglutide) for the treatment of type 2 diabetes.” Retrieved from: https://investor.lilly.com/news-releases/news-release-details/fda-approves-additional-doses-trulicityr-dulaglutide-treatment

Frias, Juan P; Bonora, Enzo; Nevarez Ruiz, Luis A; et al. (2020). “357-OR: Efficacy and Safety of Dulaglutide 3mg and 4.5mg vs. Dulaglutide 1.5mg: 52-Week Results from AWARD-11.” Retrieved from: https://diabetes.diabetesjournals.org/content/69/Supplement_1/357-OR