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SGLT2 inhibitors: A new class of medications to consider

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The current medication management recommendations for people with type 2 diabetes includes an extensive list of options, and has recently added ‘a new member’ to this group.

 

By Shelley Diamond, BScPhm

Illustration by Martin Bregman

 

In May of this year, Health Canada approved canagliflozin (Invokana™), the first in a new class of medications called sodium glucose co-transporter 2 (SGLT2) inhibitors. SGLT2 inhibitors use a different approach to controlling blood glucose levels at a different site involved in glucose regulation: the kidney. The mechanism by which this occurs is that SGLT2, the transporter, is inhibited and this reduces the reabsorption of filtered glucose and increases urinary glucose excretion, which results in a reduction in blood glucose levels. SGLT2 is responsible for at least 90% glucose reabsorption in the kidney.

Place in therapy

Canagliflozin is currently indicated as an adjunct to diet and physical activity to improve glycemic control in patients with type 2 diabetes. It has been studied in clinical trials as monotherapy, in combination with metformin and in combination with other antihyperglycemics, including insulin. In addition to improved glucose control, canagliflozin also improved body weight and systolic blood pressure.  Canagliflozin also has the benefit of having a low risk of hypoglycemia.

Use

Canagliflozin is an oral medication taken once daily. It is currently not recommended for use in children, type 1 diabetes or diabetic ketoacidosis. The drug is contraindicated for those patients receiving hemodialysis, those who have severe renal dysfunction, or those who have a history of severe hypersensitivity to canagliflozin. The recommended starting dose is 100mg taken 30 minutes before the first meal of the day. This dose can be increased to 300mg daily for those not reaching target blood glucose levels if they tolerate the 100mg dose and have normal renal function.

Canagliflozin levels are reduced when administered with inducers of the UDP-glucuronosyl transferase (UGT) enzyme (e.g. rifampin, phenytoin, phenobarbital, ritonavir). In these instances, the dose should be increased to 300mg for those tolerating 100mg daily and who have an eGFR ≥ 60mL/min/1.73m2 and need additional glycemic control.

Adverse effects

The drug has been generally well tolerated. The most common adverse effects are genital fungal infections, urinary tract infections and increased urination. It can also cause dehydration, orthostatic hypotension, postural dizziness and hypotension which is usually seen in people over 75 years of age, or in those with kidney problems and people taking diuretics. Canagliflozin can also cause an increase in LDL cholesterol.

What to monitor

In addition to monitoring for genital mycotic infections and UTIs, patients should also be checked at the start and then periodically for changes in potassium, magnesium, phosphorus and renal function. Blood pressure should be monitored since it can be impacted by volume depletion. Blood glucose should also be monitored since this will provide feedback on the efficacy and safety of canagliflozin.

In the past, we have typically considered the kidney to be an organ of elimination and a regulator of salt and ion balance. In recent years, the kidney’s contribution to glucose regulation has been recognized. This novel class provides a new approach to manage hyperglycemia in type 2 diabetes patients with the added benefits of not causing hypoglycemia, promoting weight loss and potentially reducing blood pressure. Watch for more newcomers to the group in the coming years!