Q I have noticed that many of my patients with Type 2 diabetes are on SGLT2 inhibitors. What do I need to know about this drug?

The pathophysiology of Type 2 diabetes includes insulin resistance, hepatic production of glucose, and decreased insulin secretion. Medications that work with each component have included metformin, glitazones, sulfonylureas, and insulin. The use of these medications is limited by gastrointestinal side effects, weight gain, and hypoglycemia. A new class of antidiabetic drugs, sodium glucose transporter 2 inhibitors (SGLT2), offers another approach to glycemic control.

In the kidney, glucose and sodium are filtered through the glomeruli and reabsorbed in the proximal tubules via active transport. SGLT2 is responsible for 90% of the reabsorption of both glucose and sodium. Medications that inhibit reabsorption lower the renal threshold for glucose, which results in increased glucose excreted in the urine. Decreased reabsorption and increased excretion of glucose result in lower blood glucose and loss of calories (Haas et al., 2014).

The drugs in this class, called gliflozins, lower circulating glucose and promote weight loss. They are an adjunct to diet and exercise and are used alone or added to other oral diabetes medications and/or insulin. Although, the gliflozins are not approved for use in Type 1 diabetes, there are studies underway to prove their efficacy and safety. Currently, there are three medications that are approved for use in the Unites States. These include Dapagliflozin (Farxiga), 5 to 10 mg; Canagliflozin (Invokana), 100 to 300 mg; and Empagliflozin (Jardiance), 10 to 25 mg.

Gliflozins are contraindicated with severe renal impairment. The amount of glucose filtered in the kidney is dependent on the amount of glucose in the blood and the glomerular filtration rate. Impaired renal function is not a risk to the patient; however, the medication will have a decreased effect due to the decreased filtration rate. Assessing renal function prior to initiation of therapy is recommended.

Although gliflozines are not an antihypertensive therapy, there may be a decrease in blood pressure, which may be beneficial for those with hypertension. Osmotic diuresis with water and sodium loss can result in hypotension. The diuresis can increase blood viscosity (increase Hgb/Hct), but the thirst mechanism is not activated because there is not an increase in sodium. The elderly and those on diuretics should be monitored for dehydration. Educating patients to avoid dehydration with adequate fluids and understand symptoms of dehydration such as dizziness, fainting, lightheadedness, weakness, and orthostatic hypotension is important.

Glucose is a nutrient for bacteria. Induced glycosuria increases the risk for urinary tract infections as well as genital yeast infections. Teaching symptoms of yeast infections should include vaginal odor, white or yellow discharge, and itch for women; and penis redness, swelling, itch, rash, and foul-smelling discharge for men. Other precautions include the potential for an increased low-density lipoprotein cholesterol with the need to monitor and treat as appropriate. Use with insulin and insulin secretagogues may result in hypoglycemia. Lowering the dose of these agents may be required to reduce this risk. For those patients taking potassium sparing diuretics, monitor for hyperkalemia.

Other education tips for patients:

1. You will see sugar in the urine with testing.

2. Take medication with or without food one time/day.

3. If you miss a dose, take it when you remember, but never take two at the same time.

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