Summary Safety Review - SGLT2 inhibitors - Assessing the potential risk of a rare brain condition (posterior reversible encephalopathy syndrome) in patients who have developed high levels of acids in the blood (diabetic ketoacidosis)  

February 8, 2018

Product

SGLT2 inhibitors (canagliflozin, dapagliflozin, and empagliflozin)

Potential Safety Issue

Rare brain condition (posterior reversible encephalopathy syndrome) in patients who have developed high levels of acids in the blood (diabetic ketoacidosis)

Key Messages

• SGLT2 inhibitors are prescription drugs authorized for sale in Canada to lower blood sugar in adults with type 2 diabetes. They work by helping remove excess sugar from the body through the urine.
• After receiving two Canadian case reports, Health Canada reviewed the potential risk of posterior reversible encephalopathy syndrome (PRES) in patients treated with SGLT2 inhibitors who had developed diabetic ketoacidosis (DKA).
• Health Canada’s review of the available information did not find a link between the use of SGLT2 inhibitors and the risk of PRES in patients who have developed DKA. Health Canada will continue to monitor the safety of SGLT2 inhibitors.

Overview

After receiving two Canadian case reports involving canagliflozin, Health Canada reviewed the potential risk of PRES in patients treated with SGLT2 inhibitors who have developed DKA. SGLT2 inhibitors have been linked to an increased risk of DKA, which is a serious complication of diabetes.

Posterior reversible encephalopathy syndrome is a rare condition which can affect the brain and is characterized by sudden changes in the nervous system including headaches, confusion, seizures, and vision trouble. It can develop in association with many conditions, such as severe infection or DKA, and drugs. When PRES is caused by a drug, it is important to stop the use of the drug as soon as possible to avoid complications.

Use in Canada

• SGLT2 inhibitors are prescription drugs authorized for sale in Canada to lower blood sugar in adults with type 2 diabetes. They work by helping remove excess sugar from the body through the urine. SGLT2 inhibitors are used along with diet and exercise either alone or in combination with other specific agents that control blood sugar.
• There are currently three different SGLT2 inhibitors on the Canadian market: canagliflozin, dapagliflozin, and empagliflozin. These drugs are also available in products that combine them with other drugs that treat type 2 diabetes.
• Canagliflozin was the first SGLT2 inhibitor sold in Canada in 2014. In 2016, there were around 1.5 million prescriptions of SGLT2 inhibitors filled in Canada.

Safety Review Findings

• At the time of the review, Health Canada had received two unique Canadian^{Footnote a}  reports of PRES in patients treated with SGLT2 inhibitors who had developed DKA. Both reports involved canagliflozin and suggested that PRES could possibly be associated with the drug. However, other risk factors such as DKA and severe infection could have played a role in the events.
• A search in the World Health Organization database for reports of PRES with the use of SGLT2 inhibitors did not identify any additional reports.
• A search for published information found no additional reports or other evidence for a link between SGLT2 inhibitors and PRES.

Conclusions and Actions

• Health Canada’s review of the available information did not find enough evidence to make a link between the use of SGLT2 inhibitors and the risk of PRES in patients who have developed DKA.
• Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of these health products.
• Health Canada will continue to monitor safety information involving SGLT2 inhibitors, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified.

Additional Information

The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of these drugs both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.