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SGLT2 Inhibitors: A New Class of Diabetes Medications

Sep 19, 2018

Author: David L. Joffe, BSPharm, CDE, FACA

What is a SGLT2 Inhibitor?

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, also called gliflozin drugs,  are a new class of diabetic medications indicated for the treatment of type 2 diabetes. They have also been found to show cardiac benefits in patients with diabetes, and are being studied for possible use in type 1 diabetes. They work by reducing the absorption of glucose via the kidneys so that excess glucose is excreted through urination.

In conjunction with exercise and a healthy diet, they can improve glycemic control. They have been studied alone and with other medications including metformin, sulfonylureas, nizagara 100, pioglitazone, and insulin.


Editor’s Note: Since we first looked at this new drug class in April 2013, numerous studies have been done on the benefits and risks of the SGLT2 inhibitors. See below for a roundup of the new information, including the latest investigational drug in this class, Ertugliflozin.

How SGLT2 Inhibitors Work

SGLT2 is a protein in humans that facilitates glucose reabsorption in the kidney. SGLT2 inhibitors block the reabsorption of glucose in the kidney, increase glucose excretion, and lower blood glucose levels.



SGLT2 is a low-affinity, high capacity glucose transporter located in the proximal tubule in the kidneys. It is responsible for 90% of glucose reabsorption. Inhibition of SGLT2 leads to the decrease in blood glucose due to the increase in renal glucose excretion. The mechanism of action of this new class of drugs also offers further glucose control by allowing increased insulin sensitivity and uptake of glucose in the muscle cells, decreased gluconeogenesis and improved first phase insulin release from the beta cells.

It is proposed that in prehistoric times, we developed an elegant system for maximizing energy conservation and storage, due to lack of consistent food supplies. This system included reducing the activity of our neurological endocrine system to slow metabolism and conserve the stored energy in our bodies, as well as a method to increase reabsorption of excess glucose that was removed by the kidneys.

Now that the majority of our type 2 patients have an adequate or most likely an over-abundant supply of glucose from the foods we eat this system is no longer necessary for survival and in fact contributes to increased weight and diabetes risk. The first of the defects was addressed in May of 2009 when Cycloset (bromocriptine mesylate rapid release) was approved by the FDA and now with the approval of Invokana (canagliflozin), Jardiance (empagliflozin), and Farxiga (dapagliflozin), we have medications to address the second half of this problem.

Drugs in the SGLT2 inhibitors class include empagliflozin, canagliflozin, dapagliflozin, ipragliflozin (which has not yet been approved for use in the U.S.). At this time canagliflozin is the only drug in this class approved by the FDA for the treatment of type 2 diabetes.

Vaginal yeast infections and urinary tract infections are the most common side effects associated with canagliflozin with the greatest risk being in female patients and those men who are uncircumcised.

There is also an increased desire to urinate and the medication is not indicated in patients with type 1 diabetes, or patients with frequent ketones in their blood or urine, severe renal impairment, end stage renal disease or patients receiving dialysis. Patients should be advised to expect glucose to be in the urine and if they are using urine glucose strips that they will have a positive reading most of the time.

 Current SGLT2 Inhibitors News (as of September, 2017)
In September of 2017, the results of Phase 3 trials of a new investigational SGLT2 inhibitor, Ertugliflozin, were announced at the European Association for the Study of Diabetes 2017 Annual Meeting. Ertugliflozin, developed to improve glycemic control in adults with type 2 diabetes, met the primary outcomes in two yearlong phase 3 trials, VERTIS SU and VERTIS SITA2.
This follows an exciting few years in SGLT2 inhibitor news. Warnings about risk of amputation and ketoacidosis associated with the drugs raised concern. The possibility that SGLT2s may be useful for type 1 diabetes as well as type 2 is being investigated. Perhaps the most important issue concerning the SGLT2 inhibitors is their beneficial effects on heart health.

To review all the the important research being done about SGLT2 inhibitors, visit our SGLT-2 Resources


“Canagliflozin Provided Substantial and Sustained Glycemic Improvements as Monotherapy and in Add-On Combinations in Adults with Type 2 Diabetes in Five Phase 3 Studies.” Johnson & Johnson. Jansen Research & Development, 09 June 2012. Web. 02 Apr. 2013.

Clarke, Toni. “FDA Approves Johnson & Johnson Diabetes Drug, Canagliflozin.” Reuters. Thomson Reuters, 29 Mar. 2013. Web. 01 Apr. 2013.

“Diabetes Treatment, Part 2: Oral Agents for Glycemic Management.” Clinical Diabetes. N.p., Oct. 2007. Web. 12 Apr. 2013.

FDA Approves Invokana to Treat Type 2 Diabetes. N.p., n.d. Web. 01 Apr. 2013

“Invokana.” INVOKANA™ (Canagliflozin) Treatment for Type 2 Diabetes. N.p., n.d. Web. 12 Apr. 2013

Nainggolan, Lisa. “FDA Approves Canagliflozin, a First-in-Class Diabetes Drug.” Medscape Log In. N.p., 29 Mar. 2013. Web. 01 Apr. 2013.


— Marina Farid, PharmD Candidate, FAMU College of Pharmacy also contributed to this article.


Last updated Sept. 18, 2018