Pharmacist counting pills
In March, 2013, the U.S. Food and Drug Administration approved the first agent in a new class of diabetes drugs: canagliflozin. It’s sold in the U.S. as Invokana. So we now have 12 classes of drugs for treating diabetes. In January 2014 the second drug in this class was approved: dapagliflozin or Farxiga. Empagliflozin ( U.S. brand name: Jardiance) was approved in August, 2014. Ertugliflozin (U.S. brand name: Steglatro) was approved in early 2018 or so. Other SGLT2 inhibitors are in the pipeline.
This review is quite limited—consult your physician or pharmacist for full details. Remember that drug names vary by country and manufacturer. My info source is the manufacturers’ package inserts. Any of this information could change at any time.
Sodium-glucose co-transport 2 inhibitors, or SGLT2 inhibitors.
How Do They Work?
Our kidneys filter glucose (sugar) out of our bloodstream, then reabsorb that glucose back into the bloodstream. (Don’t ask me why.) SGLT2 inhibitors impair that reabsorption process, allowing some glucose to be excreted in our urine. You could call it a diuretic effect. Dapagliflozin at a dose of 10 mg/day, for example, causes the urinary loss of 70 grams of glucose daily.
These drugs are for adults with type 2 diabetes, to be used in combination with diet and exercise. They can be used alone or in combination with some of the other diabetes drugs, possibly to include insulin, metformin, sulfonylureas, or pioglitazone. Dapagliflozin has also been tested in combination with sitagliptin, a DPP4-inhibitor. Clinical experience in combination with other diabetes drugs is very limited.
Canagliflozin starts at 100 mg by mouth daily, taken before the first meal of the day. Dose can be increased to 300 mg daily. Dapagliflozin dosing starts at 5 mg by mouth every morning, with or without food, and can be increased up to 10 mg once daily. Start empagliflozin at 10 mg every AM, and max out at 25 mg every AM if needed. Ertugliflozin starts at 5 mg daily and can go up to 15 mg/day.
The most common side effects are vaginal yeast infections (about 5% of women), urinary tract infections, and penile yeast infections (e.g., balanitis). Also noted are increased urination, and dizziness or fainting from low blood pressure after arising to stand (orthostatic hypotension). The low blood pressures are related to a diuretic effect of this class.
Hypoglycemia (low blood sugar) is quite uncommon, perhaps nonexistent, unless these drugs are used with other drugs that often cause hypoglycemia, such as insulin and insulin secretagogues like sulfonylureas.
High potassium levels may be seen with canagliflozin. All three can cause elevations of LDL cholesterol (“bad cholesterol”).
Dapagliflozin and empagliflozin may cause elevations of creatinine in the blood, a warning that kidney function may be impaired.
Canagliflozin seems to promote weight loss, which may be welcome by some. It also doubles the risk of leg and foot amputations when compared to placebo. Ertugliflozin is also linked to increased risk of lower limb amputation.
Don’t Use If You . . .
- have diabetic ketoacidosis
- are pregnant or planning to get pregnant
- have advanced or severe kidney disease
- have severe liver impairment (glomerular filtration rate under 60 ml/min/1.73 m-squared, at least for dapagliflozin)
- have type 1 diabetes
- are on dialysis
- are a nursing mother
- for dapagliflozin: active bladder cancer (and use caution if you have history of bladder cancer)
Update: In 2019, the FDA approved an SGLT2 inhibitor in pill form, called semaglutide and sold in the U.S. as Rybelsus.
Updated September 26, 2019