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Could SGLT2 Inhibitors Be Part of a New Treatment for Type 1 Diabetes?

The main function of the kidneys is to filter the blood’s metabolic end-products and direct everything your body doesn’t need toward the bladder. Essential elements such as glucose are filtered during the first step of the filtration process. So, when blood sugar levels are below 10–12 mmol/L, the kidneys will re-absorb all the glucose before urine reaches the bladder.

Empagliflozin, dapagliflozin and canagliflozin are drugs that can stop the kidneys from reabsorbing the glucose, so that the glucose can be eliminated through urine instead of passing through the blood, thereby reducing blood sugar levels. These drugs are classified as sodium-glucose transport protein 2 inhibitors (SGLT2 inhibitors) and can help patients with type 2 diabetes (T2D) to better control their blood sugar levels. New data suggests that they could also help with type 1 diabetes (T1D) management.   

Proven and approved drugs for people with type 2 diabetes

People with T2D generally present with comorbidities, such as obesity, and are at a high risk of kidney and heart disease. Some of these complications can be prevented in the long term with proper T2D management.

Several studies have shown how the average T2D patient can benefit from taking SGLT2 inhibitors in several ways: better blood sugar control, weight loss, lower blood pressure, and considerably lower risk of developing kidney and cardiovascular complications. For instance, SGLT2 inhibitors reduce the hospitalization rate for heart failure and curb the progression of pre-existing kidney disease.

Potential use as a treatment for type 1 diabetes

Considering that the mode of action of SGLT2 inhibitors doesn’t interfere with that of insulin and that they have been effective in T2D patients, researchers looked at whether they would be safe and effective for people with T1D. Many aspects have yet to be studied, but the results so far are encouraging. 

In one study, the hemoglobin A1c (Hb1AC) of participants with T1D was reduced by about 0.5% with no higher risk of hypoglycemia. People with T1D could also possibly benefit from the same positive effects on their weight and their kidney and heart health than those observed among T2D individuals.

Some potential risks still need to be assessed. The main one is a higher risk of genital mycosis (vaginitis in women, and balanitis in men). The reduced need for insulin caused by SGLT2 inhibitors could prompt another rare but serious side effect: diabetic ketoacidosis. Diabetic ketoacidosis is an emergency situation that occurs when the body lacks insulin and is unable to convert glucose into energy, which makes it  start to use stored fat as a source of energy. The conversion of stored fat into energy releases ketone bodies into the bloodstream. When in high quantity, ketone bodies are toxic to the body. See BETTER’s PDF resources on the management of ketone bodies.

For patients who use a SGLT2 inhibitor, diabetic ketoacidosis can occur with blood sugar values that are much lower, so it’s easier to miss it.

Who could use it?

A tool has been developed as part of one study in order to help healthcare professionals decide whether or not they should prescribe a SGLT2 inhibitor. But these drugs are not yet available for T1D individuals in Canada, so the tool wouldn’t be useful right now for Canadians. However, the drugs have been authorized in other countries, for instance in Europe.

In short, SGLT2 inhibitors could be prescribed for patients who meet the following criteria:

  • Between 18 and 75 years of age
  • Commitment to monitor ketone bodies and blood sugar levels adequately
  • Good renal function
  • Overweight (BMI > 27). These individuals are at a higher risk of kidney and heart disease and could benefit from losing some weight.
  • Total daily dose of insulin > 0.5 unit/kg, since the risk for ketoacidosis seems to be lower above this dosage.

Health Canada is expected to rule on whether or not SGLT2 inhibitors can be used by T1D patients in the next year. 

The BETTER project aims to promote the best up-to-date treatments for type 1 diabetes in Quebec.

If you wish to participate, sign up for the BETTER registry.

References

  • Diabetes Canada. (2015). SGLT2 Inhibitors [PDF file]. Retrieved from https://www.diabetes.ca/DiabetesCanadaWebsite/media/Managing-My-Diabetes/Tools%20and%20Resources/Medication-Sheet-SGLT2.pdf?ext=.pdf 
  • Evans, M., Hicks, D., Patel, D., Patel, V., Mcewan, P., Dashora, U. (2019). Optimising the Benefits of SGLT2 Inhibitors for Type 1 Diabetes. Diabetes Therapy, 11(1), 37-52. doi:10.1007/s13300-019-00728-6
  • Mathieu, C., Van Den Mooter, L., Eeckhout, B. (2019). Empagliflozin in type 1 diabetes. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2019:12 1555–1561 1. https://doi.org/10.2147/DMSO.S194688
  • Health Canada. (2017). SGLT2 Inhibitors [INVOKANA (canagliflozin), FORXIGA (dapagliflozin), XIGDUO (dapagliflozin/metformin), JARDIANCE (empagliflozin)] – Risk of Diabetic Ketoacidosis. Retrieved from https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2016/58404a-eng.php
  • Zelniker, T. A., Wiviott, S. D., Raz, I., Im, K., Goodrich, E. L., Bonaca, M. P., Sabatine, M. S. (2019). SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: A systematic review and meta-analysis of cardiovascular outcome trials. The Lancet, 393(10166), 31-39. doi:10.1016/s0140-6736(18)32590-x