'Good News' From the FDA: Label Changes for Dulaglutide, Canagliflozin

Anne L. Peters, MD


October 08, 2020

This transcript has been edited for clarity.

Today I'm going to discuss two label changes from the FDA: one for dulaglutide and one for canagliflozin.

Higher Doses of Dulaglutide

The dulaglutide label change allows for two higher doses to be used in the treatment of type 2 diabetes. The data for this change came from the AWARD-11 trial, which was a phase 3, randomized controlled trial involving 1842 participants with type 2 diabetes. They compared the safety and efficacy of two new doses of dulaglutide, 3 mg and 4.5 mg, with 1.5 mg, which is the dose we traditionally use.

The data showed an increased reduction in A1c and more weight loss with the higher doses. At 1.5 mg weekly, there was a 1.5% reduction in A1c and a 6.8-lb weight loss. In the 3-mg group, there was a 1.7% reduction in A1c and a weight loss of 8.8 lb. In the 4.5-mg dose group, there was a 1.9% reduction in A1c and a weight loss of 10.4 lb.

This was not associated with an increased risk for side effects, but I suggest going up slowly to help patients avoid getting the GI side effects that we see with these agents. I would start with 0.75 mg once a week for a month, then use 1.5 mg for a month, then 3 mg for a month. If you need to continue upward, use the 4.5-mg dose from there on.

These label changes and these new formulations should be on the market soon. This provides another option for your patients who need more A1c reduction and a higher dose of a GLP-1 receptor agonist.

Black Box Warning Dropped for Canagliflozin

In regard to canagliflozin, the FDA dropped the black box warning regarding lower-extremity amputation. This is really good news because it means that the danger is not what we once thought it was. The FDA says they reviewed new data from the clinical trials that demonstrate additional heart- and renal-related benefits of canagliflozin, and they determined that amputation risk, while still increased, is lower than previously thought.

The FDA now recommends that patients on canagliflozin receive preventive foot care and be monitored for any changes, such as pain, tenderness, soreness, ulcers, and infections in the legs and feet. Obviously, if you have a patient who is at very high risk for amputation or who has had amputation, you really need to weigh risks and benefits.

The FDA says that prescribers should weigh a patient's risk for amputation when selecting antidiabetes medicines. It is still on the label, but it's not a black box warning. Again, this is good news because the FDA says the risk isn't as high as they once thought.

I'm Dr Anne Peters for Medscape. Thank you.

Anne L. Peters, MD, is a professor of medicine at the University of Southern California (USC) Keck School of Medicine and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations.

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