Summary Safety Review - Sodium/glucose cotransporter 2 (SGLT2) inhibitors - Assessing the potential risk of inflammation of the pancreas (acute and chronic pancreatitis)

Review decision

A Summary Safety Review complements other safety related information to help Canadians make informed decisions about their use of health products. Each summary outlines what was assessed in Health Canada’s review, what was found and what action was taken by Health Canada, if any.


Issued: 2018-07-20

Product

SGLT2 inhibitors (canagliflozin, dapagliflozin and empagliflozin)

Potential Safety Issue

Inflammation of the pancreas (acute and chronic pancreatitis)

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 by eliminating it through the urine.
  • Health Canada reviewed the potential risk of pancreatitis with the use of SGLT2 inhibitors because of Canadian reports and case reports published in the scientific literature that indicated a possible link.
  • Health Canada's review of the available information concluded that there may be a link between the use of SGLT2 inhibitors and the risk of acute pancreatitis. However, there was limited evidence to suggest a link with chronic pancreatitis.
  • Health Canada is working with the manufacturers to update the product safety information for SGLT2 inhibitors to inform healthcare professionals and patients about this risk.

Overview

Pancreatitis is an inflammatory disease of the pancreas. It is s most commonly caused by gallstones and alcohol use, but can also be caused by a reaction to a drug (drug-induced pancreatitis). Acute pancreatitis is characterized by a sudden onset of abdominal pain which is often severe, while chronic pancreatitis is, in most cases, characterized by repeated or on-going abdominal pain which can develop after repeated episodes of acute pancreatitis.

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 by eliminating it 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 4 different SGLT2 inhibitors on the Canadian market: canagliflozin, dapagliflozin, empagliflozin and ertugliflozina. These drugs are also available in combination with other drugs that treat type 2 diabetes.
  • In 2014, canagliflozin was the first SGLT2 inhibitor sold in Canada. In 2016, the most recent data year available, there were more than 2 million prescriptions of SGLT2 inhibitors filled in Canada.

Safety Review Findings

  • At the time of the review, Health Canada had received 20 Canadian reportsb of acute pancreatitis related to the use of SGLT2 inhibitors and no reports of chronic pancreatitis. Of these reports, 1 was further assessed as it met the criteria defined for this review. This Canadian report showed a possible link between acute pancreatitis and the use of an SGLT2 inhibitor.
  • The review also looked at 476 international reports and 6 published cases of pancreatitis related to the use of SGLT2 inhibitors. Of these reports, 28 cases of acute pancreatitis, but no cases of chronic pancreatitis, were further assessed as they met the criteria defined for this review. Of the 28 reports, 18 showed a possible link between acute pancreatitis and the use of a SGLT2 inhibitor. In most of the remaining reports, other medical conditions and medications could have caused the pancreatitis.
  • A review of the scientific literature did not find any published studies that showed an increased risk of pancreatitis in patients treated with SGLT2 inhibitors.
  • Product safety information in the United States and the European Union do not contain any information specific to pancreatitis.

Conclusions and actions

  • Health Canada's review concluded that there may be a link between the use of SGLT2 inhibitors and acute pancreatitis.
  • Health Canada is working with the manufacturers to update the product safety information on SGLT2 inhibitors to inform about this risk.
  • Health Canada will continue to monitor safety information involving SGLT2 inhibitors to identify and assess potential harms, as it does for all health products on the Canadian market. 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 information, and what is known about the use of this drug both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

Footnotes

  1. Ertugliflozin was not assessed in this review as it was authorized for sale after Health Canada decided to review the potential risk of inflammation of the pancreas with SGLT2 inhibitors
  2. Canadian reports can be accessed through the Canada Vigilance Online Database.

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