Diabetes is a chronic disease with serious complications. Although we have known about diabetes for over 2500 years, there was no treatment until 1900s. In 1921 Insulin was first invented by Banting and Best winning a Nobel prize. Information and understanding of this serious illness was limited until recently and there were not many options to treat diabetes. Today, we know much more about diabetes, related complications and furthermore the treatment options.
When I was in medical school, we learned about just two problems, insulin resistance and pancreatic inability to produce enough insulin to overcome this resistance. Today we know several different pathways contributing to high blood sugars.
We have known about the role of kidneys in diabetes since Indian doctors called it madhu meha meaning sweet urine over 2500 years ago. Kidneys get rid of excess glucose from human body by excreting it in the urine. A non diabetic will start to spill glucose in urine once his/her blood glucose is higher than 180mg/dl but in a diabetic individual this threshold is shifted upward to 240mg/dl which means they continue to reabsorb sugar even when their blood glucose is already high.
SGLT2 inhibitors are an exciting new drug class that affects completely new pathway previously unexplored to treat diabetes. SGLT2 are basically these small doors through which glucose re-enters the blood stream from kidney tubules. The SGLT2 inhibitors block these doors resulting in excretion of glucose through the kidneys in urine. The first one in the class was canagliflozin. There are several other agents in the drug class manufactured by several different companies including dapagliflozin and empagliflozin. There are some in pipeline.
This interesting pathway was first discovered after the observation of familial renal glucosuria which is a naturally occurring genetic mutation leading to glucose loss in the urine with non-functioning SGLT2 receptors in the kidneys. These patients go through life without every having diabetes or kidney disease.
SGLT2 inhibitors have been studied by themselves in comparison to placebo, with glucophage, with glucophage and sulphonylureas and with other anti-diabetic drugs including insulins. SGLT2 inhibitors not only reduce blood glucose but they also help with weight loss and lowering blood pressure. Recently one SGLT2 agent showed reduction in cardiovascular mortality.
As you can imagine, SGLT2 inhibitors increase sugar in the urine and thus they can lead to some side effects including increased risk for urinary tract infections, genital mycotic infections, increased thirst, constipation, hypotension and dizziness. SGLT2 inhibitors will not help a patient if their kidneys are not working. When anyone starts this medicine, they need to drink plenty of water and cut back on blood pressure medications. Patients and providers also need to be aware of how these medicines are metabolized and excreted and their possible interactions with other medications.
Hope you enjoyed learning about the new exciting drug class to treat diabetes.