Blog Viewer

SGLT2 inhibitors and DKA

By Michelle Mielke posted 05-28-2015 14:07

  

Not long ago a new class of diabetes medication, SGLT2 inhibitors, was approved by the FDA and the first product came to market under the name Invokana (canagliflozin). The way these medications work is that they prevent the kidneys from reabsorbing as much of the sugar from food and ultimately increasing urination. This also results in fewer calories being absorbed which leads to some pretty good weight loss. There are now two other medications in this class, Farxiga (dapagliflozin) and Jardiance (empagliflozin) plus a number of combination drugs.

From the time this drug class became available, the endocrinologists in my clinic have been divided about prescribing this medication. Part of the thought is that it gives the patient the impression that they don't have to work at weight loss. Anyone who has ever had to lose weight can attest to the fact that that is not the case. But there has also been some concern about possible long term stress to the kidneys and the possibility of the drug excelerating kidney disease progression. Research studies did not indicate any issues with kidney function in persons with normal kidney function at onset, but the longest studies were only for a few years. The main side effect identified at the time of launch was increased risk of urinary tract infections because of the increased amount of sugar in the urine. However, after being on the market for about a year or so, a new and very unexpected side effect has entered the spotlight, DKA absent high blood sugars.

At UNC we had been doing some off label use of the SGLT2 inhibitors in people with Type 1 diabetes and patients started having nausea, vomiting, difficulty breathing with high temperatures. All the signs and symptoms of DKA, but their blood sugars were under 200 mg/dL. When tested for ketones, they tested positive with moderate to high ketones. In the past few months, as this side effect has become more well known, DKA has been found even in people with Type 2 diabetes on this medication.

The mechanism for the DKA is not yet fully understood and the SGLT2 inhibitors may still have a place in diabetes management. The question remains whether all patients on SGLT2 inhibitors should be testing for ketones, but as diabetes educators, we need educate to the patients about this side effect and be diligent about inquiring about symptoms of DKA at each visit for patients with Type 2 diabetes who are taking one of these medications to identify any issues as quickly as possible.

3 comments
2 views

Comments

07-23-2015 09:53

Thoughts on DKA warning?

I've been noticing a bit more talk about the risks of SGLT2's and DKA in the last few weeks and wanted to see if anyone had any thoughts.  The endocrinologists at my clinic were discussing a case of DKA with blood sugars < 200 in a patient with Type 2 (although the warnings mainly only mention it for Type 1), and then I received a letter from Janssen, AstraZeneca, and Lilly warning providers to be aware of the risk. 

Has anyone else had some unusual cases of DKA, and do you or the providers you work with have any thoughts on which patients to be especially cautious in using these products with?

05-30-2015 12:19

Great info

I wish I had read this Thursday!!!  I went to a talk about Invokana and was able to ask a bunch of questions, but didn't know about this potentail to ask.

Great information.  I will have to remember for the next time.

-Chris 

05-29-2015 15:35

SGLT2

Very interesting. I eagerly await the findings on the pathophysiology of the DKA