Updated June 16, 2015.
Written or reviewed by a board-certified physician. See About.com's Medical Review Board.
Just as I was gearing up to discuss a new oral medication proven to effectively lower glucose levels in patients with type 1 diabetes, the FDA released a warning against the entire class of drugs. Sigh…
Well, regardless, let me introduce the sodium- glucose co-transporter (SLGT-2) inhibitors. This new class of medications tackles high blood glucose levels by blocking transporters, aptly named SGLT-2s, which lead to the reabsorption of glucose from the kidneys into the blood stream.
As a result of this blockage, sugar that might have otherwise lead to high blood glucose readings instead gets flushed down the toilet. In addition to the benefit of better hemoglobin A1C readings, these drugs also lead to significant weight loss and decreases in blood pressure.
These drugs were FDA approved for type 2 diabetes in early 2013 and include medications such as Canagliflozin (Invokana), Dapagliflozin (Farxiga), and Empagliflozin (Jardiance). While these medications are not yet approved for type 1 diabetes, small studies have shown that SLGT-2 inhibitors may also improve glycemic control in type 1 diabetes. This would be revolutionary, in my opinion, since they would be the first oral medications to effectively lower blood sugars in type 1 diabetes.
On May 15th, 2015, however, the FDA came out with a warning that these medications may also lead to a condition called diabetic ketoacidosis (DKA). Ketoacidosis is a serious condition that occurs in people with diabetes when chemicals called “ketones” build up in the bloodstream.
Normally, the body uses sugar as a source of energy, and the hormone, insulin, allows this process to take place. When insulin levels are low, the body is unable to utilize sugar for energy and instead breaks down fat. However, when the body burns too much fat, ketones can build up in the blood stream and become toxic. Signs of DKA include extreme thirst, frequent urination, nausea or vomiting, fatigue, difficulty concentrating, weight loss, and fruity-smelling breath.
The DKA warning came out after a search of the FDA Adverse System database identified 20 cases of DKA in patients treated with SGLT-2 inhibitors from March 2013 until June 2014. All patients with DKA required either Emergency Room visits or hospitalizations. The median time to onset was two weeks with a range of 1-175 days.
SLGT-2 inhibitors can potentially trigger DKA by lowering glucose in the absence of increased insulin: as blood glucose levels are lowered through glucose excretion in the urine, the liver responds by breaking down the storage form of glucose into active glucose. Next in line, muscle and fat is broken down into glucose. Once too much fat has been broken down, ketone levels begin to rise and DKA occurs.
We don’t know yet the frequency of DKA in patients taking SGLT-2 inhibitors, but we know that it can occur with both type 1 and type 2 diabetes. Interestingly, DKA is usually associated with very high sugars, but sugars are generally normal or only slightly elevated when DKA occurs in the setting of SLGT-2 inhibitor use.
While there are many possible benefits from the use of SLGT-2 inhibitors, patients need to be educated about the possibility of DKA. And since the risk of this potentially fatal complication from SLGT-2 inhibitors appears to be compounded by already low or absent insulin levels, I have yet to prescribe any SLGT-2 inhibitors for patients with type 1 diabetes. The “revolutionary” potential of this medication for type 1 diabetes will need to await further studies demonstrating not only its efficacy but its safety.
Written or reviewed by a board-certified physician. See About.com's Medical Review Board.
Just as I was gearing up to discuss a new oral medication proven to effectively lower glucose levels in patients with type 1 diabetes, the FDA released a warning against the entire class of drugs. Sigh…
Well, regardless, let me introduce the sodium- glucose co-transporter (SLGT-2) inhibitors. This new class of medications tackles high blood glucose levels by blocking transporters, aptly named SGLT-2s, which lead to the reabsorption of glucose from the kidneys into the blood stream.
As a result of this blockage, sugar that might have otherwise lead to high blood glucose readings instead gets flushed down the toilet. In addition to the benefit of better hemoglobin A1C readings, these drugs also lead to significant weight loss and decreases in blood pressure.
These drugs were FDA approved for type 2 diabetes in early 2013 and include medications such as Canagliflozin (Invokana), Dapagliflozin (Farxiga), and Empagliflozin (Jardiance). While these medications are not yet approved for type 1 diabetes, small studies have shown that SLGT-2 inhibitors may also improve glycemic control in type 1 diabetes. This would be revolutionary, in my opinion, since they would be the first oral medications to effectively lower blood sugars in type 1 diabetes.
On May 15th, 2015, however, the FDA came out with a warning that these medications may also lead to a condition called diabetic ketoacidosis (DKA). Ketoacidosis is a serious condition that occurs in people with diabetes when chemicals called “ketones” build up in the bloodstream.
Normally, the body uses sugar as a source of energy, and the hormone, insulin, allows this process to take place. When insulin levels are low, the body is unable to utilize sugar for energy and instead breaks down fat. However, when the body burns too much fat, ketones can build up in the blood stream and become toxic. Signs of DKA include extreme thirst, frequent urination, nausea or vomiting, fatigue, difficulty concentrating, weight loss, and fruity-smelling breath.
The DKA warning came out after a search of the FDA Adverse System database identified 20 cases of DKA in patients treated with SGLT-2 inhibitors from March 2013 until June 2014. All patients with DKA required either Emergency Room visits or hospitalizations. The median time to onset was two weeks with a range of 1-175 days.
SLGT-2 inhibitors can potentially trigger DKA by lowering glucose in the absence of increased insulin: as blood glucose levels are lowered through glucose excretion in the urine, the liver responds by breaking down the storage form of glucose into active glucose. Next in line, muscle and fat is broken down into glucose. Once too much fat has been broken down, ketone levels begin to rise and DKA occurs.
We don’t know yet the frequency of DKA in patients taking SGLT-2 inhibitors, but we know that it can occur with both type 1 and type 2 diabetes. Interestingly, DKA is usually associated with very high sugars, but sugars are generally normal or only slightly elevated when DKA occurs in the setting of SLGT-2 inhibitor use.
While there are many possible benefits from the use of SLGT-2 inhibitors, patients need to be educated about the possibility of DKA. And since the risk of this potentially fatal complication from SLGT-2 inhibitors appears to be compounded by already low or absent insulin levels, I have yet to prescribe any SLGT-2 inhibitors for patients with type 1 diabetes. The “revolutionary” potential of this medication for type 1 diabetes will need to await further studies demonstrating not only its efficacy but its safety.