Photo by Stevepb. Taken from Pixabay.
In 2014, a new antidiabetic medication was approved by Health Canada. Known as Invokana, or canagliflozin, it was the first in a new class of antidiabetic drugs known as sodium-glucose cotransporter-2 (SGLT2) inhibitors.
“For 20 years, we really did not have any new treatments that slowed down the progression of kidney disease,” said Dr. Hitesh Mehta, a staff nephrologist at the William Osler Health Center and director of the Regional Kidney Wellness Centre in Brampton, Ontario. “There has been really nothing until the development of SGLT2 inhibitors that have shown progress in slowing down kidney disease.”
Diabetes Canada—the country’s leading source for diabetes care, advocacy, as well as research—estimates that out of the three main types of diabetes, type 2 accounts for 90 to 95 per cent of diabetes cases, especially among children.
“We know diabetes is a disease that, if not controlled properly, can lead to a lot of complications, including kidney disease,” said Dr. Harpreet Bajaj, an endocrinologist and director of late-phase research at LMC Healthcare, as well as a research associate at Mount Sinai Hospital in Toronto.
Studies also show that about 40 per cent of type 2 diabetes patients are at risk of developing diabetic or chronic kidney disease. People with diabetes are at risk of suffering damage to their kidneys’ blood vessels due to high blood glucose levels and high blood pressure. This occurs over a period of time but can be avoided by taking appropriate steps.
According to Bajaj, studies conducted between 2015 and 2018 with SGLT2 inhibitors originally determined they were effective in helping people with a history of heart-related problems.
A 2019 study revealed that the use of SGLT2 inhibitors not only provided cardiovascular benefits but also proved to be an effective treatment option for patients with type 2 diabetes and diabetic kidney disease.
In Diabetes Canada’s recent clinical practice guidelines published in the Canadian Journal of Diabetes, SGLT2 inhibitors are recommended for patients with a history of heart failure and chronic kidney disease and are also proven to reduce the progression of nephropathy (kidney disease) and hospitalization resulting from heart failure.
Prior to the introduction of SGLT2 inhibitors, methods used to protect the kidneys included the glucose control and the use of angiotensin-converting enzyme (ACE) inhibitors, which help relax blood vessels and control a patient’s blood pressure.
“This is the fourth thing (SGLT2 inhibitors) we can add on to that list, which is important so we can protect people with diabetes from getting kidney complications and going off to dialysis or transplants,” Bajaj said.
Mehta said that during the big kidney disease treatment trials such as CREDENCE and DAPA-CKD, patients showed improved results such as a 30 per cent reduction in the progression to dialysis after starting on the SGLT2 inhibitors.
“We finally have drugs that are slowing down the progression of kidney disease to the point that hopefully, in the future, we'll have fewer patients on dialysis.”
Mehta said both the CREDENCE and DAPA-CKD trials finished early because the results were so positive. Currently, there is one ongoing trial, EMPA-KIDNEY, which will provide additional insights into the rest of the SGLT2 inhibitor class.
Presently, only four SGLT2 inhibitor agents are approved for use by Health Canada and the United States Food and Drug Administration. Only Invokana (canagliflozin), Forxiga® (dapagliflozin) and Jardiance (empagliflozin) are commercially available in Canada.
SGLT2 inhibitors are also not approved for use on patients with only type 1 diabetes in Canada and the United States. In Europe, Forxiga is approved as an adjunct to insulin treatment in adult patients with uncontrolled type 1 diabetes.
Bajaj said the only possible competitor for SGLT2 inhibitors is an agent called Semaglutide, which is part of the GLP1-RA class of agents. While originally only available as an injection, it is now available as an oral tablet and is approved by Health Canada. This medication has been shown to help reduce blood sugar, blood pressure and weight. While some studies suggest possible protection from heart disease, it is unknown if it provides any protection against kidney disease.
Another major benefit of the SGLT2 inhibitors, as shown in the DAPA-CKD study, is that they are not limited to just diabetic kidney disease.
Mehta said being able to use SGLT2 inhibitors on patients with non-diabetic kidney disease—with the exception of those who should not use these kinds of drugs—is a “huge breakthrough.”
“The DAPA-CKD study, which was published this year, a third of the patients did not have diabetes,” he said. “They (SGLT2 inhibitors) initially came out as diabetes drugs, but in fact, they benefit people without diabetes.”
In terms of quality of life, SGLT2 inhibitors help to reduce swelling in the legs and improve the body’s water balance. Additional benefits include lowering high blood pressure and weight loss.
Side effects of these inhibitors include the possibility of developing a yeast infection (though this is easily treatable), low blood pressure, and electrolyte imbalances. Understandably, it is not recommended for people who already suffer from low blood pressure.
The price of SGLT2 inhibitors varies between provinces and is usually between $2 to $3 a pill. They may also be covered under public reimbursement depending on the province.
With the prevalence of diabetes increasing for Canadians, Bajaj said the need for medications such as the SGLT2 inhibitors has become even more important.
“For people with diabetes, having different medication classes is important because diabetes is a complex disease and needs many different medications,” he said. “If we have medications that have low side effects like SGLT2 inhibitors and do not cause the opposite, which is low sugars or hypoglycemia, those medications are beneficial overall.”
By: Matthew Guida
As a native Montrealer, I graduated from Concordia University with a BA in Anthropology and a minor in Film Studies. I am currently studying for my master’s degree in Journalism at Carleton University in Ottawa. My interest in journalism began while attending Concordia. I was a frequent contributor to the university’s independent newspaper, The Concordian. I further honed my skills and experience by working as a List Writer for the entertainment news website Screen Rant. Since I started attending Carleton University, I have strived to further improve my skills as a journalist in not only print, but also in the fields of data, investigative and broadcast journalism. In the past year, I have also developed a growing appreciation for radio journalism and podcasts. My current interests lie in studying the future of the journalism industry, writing and researching pop culture and social media trends, as well as furthering my career in the field of journalism.