Hot Topics: SGLT2 Inhibitors and Kidney Disease

March 30, 2022, 11:13am EDT

Doctor speaking with patient

In this episode of Hot Topics in Kidney Health, Dr. Katherine Tuttle, Executive Director for Research at Providence Health Care, and Jane DeMeis, kidney patient and advocate, discuss a promising new drug that was initially developed to help patients maintain blood sugar levels and are now being used as in the prevention and treatment of kidney disease.

Diabetes and kidney disease

Diabetes is a condition in which the body has trouble controlling the level of sugar (glucose) in the blood and is a leading cause of kidney disease. It's estimated that around 30% of people with Type 1 (juvenile-onset) and 10% to 40% of those with Type 2 (adult-onset) diabetes will develop kidney failure at some point. 

Learn more about diabetes and kidney disease

What are SGLT2 inhibitors?

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a class of oral (taken by mouth) prescription medicines that are FDA-approved for use with diet and exercise to lower blood sugar in adults with type 2 diabetes. How? The drug lowers blood sugar levels by preventing the kidneys from reabsorbing sugar that is created by the body and the extra sugar leaves through in the urine. In doing so, researchers observed an unexpected benefit: the drugs also reduced the pressure on the small blood vessels of the heart and kidneys. 

How do SGLT2 inhibitors differ from other kidney disease medications?

SGLT2 inhibitors are the only class of drugs that remove extra glucose through urine, and in doing so, also protect the heart and kidneys. This caught the attention of researchers and the FDA alike. In 2020, AstraZeneca's Farxiga (dapagliflozin) was granted a Breakthrough Therapy Designation (BTD) for people with chronic kidney disease in those with and without type-2 diabetes. 

What is a Breakthrough Therapy Designation?

A BTD helps expedite the lengthy drug approval process and is only granted if early clinical evidence shows significant improvement over currently available medicines. 

In this case, dapagliflozin received a BTD because study results showed in patients with kidney disease -- with or without Type 2 diabetes -- a 39% reduction in the combined risk of:

  • kidney function becoming worse
  • start of end-stage kidney disease (ESKD)
  • kidney disease- or cardiovascular-related death

In addition, death from any cause was reduced by 31% as compared to placebo.

Who are the best candidates for SGLT2 inhibitors?

Dr. Tuttle reported that SGLT2 inhibitors are effective in treating patients with type 2 diabetes and kidney disease with an eGFR as low as 25 or 20 (stage 4). Since every patient is different, speak to your healthcare provider to see if you are a good candidate for this medicine. 

Proper diet and exercise

Both Jane and Dr. Tuttle expressed the importance of maintaining a good exercise routine and eating well, in addition to taking medications as instructed by a healthcare professional. Exercise helps patients maintain a healthy weight and control blood pressure and cholesterol. Diet is also an important part of managing kidney disease and overall health due to possible food limitations. 

Learn more about kidney diets and exercise.

Are there side effects?

During this discussion, Dr. Tuttle explained that all drugs have side effects. With SGLT2 inhibitors, there have been both positive and negative side effects reported.

Negative side effects

  • Genital yeast infections: These may occur due to the increased glucose, or sugar, in the urine. These cases can go from 3%-5% down to 2% with proper hygiene. For example, wiping front to back.  
  • Ketoacidosis: If the body doesn’t produce enough insulin, patients may experience a dangerous build-up of acids in the blood. There is a 1% chance of this side effect occurring with prevention strategies, like checking blood levels frequently and taking medicine or insulin as prescribed. 
  • Volume depletion: Because SGLT2 inhibitors increase the amount of urine produced, they can cause dehydration in some patients. However, this may benefit some patients who experience fluid overload. 

Positive side effects

  • Lower serum potassium: Kidney patients can experience hyperkalemia or dangerously high blood potassium levels. SGLT2 inhibitors can help lower potassium, protecting the patient from serious heart problems. 
  • Decreased risk of acute kidney injury: Acute kidney injury typically occurs during hospitalization for other reasons such as heart attack, severe dehydration, or sepsis, but SGLT2 inhibitors can help to lower this risk. 
  • Heart protection: Reducing pressure on blood vessels helps protect the heart. 

Cost

Currently, SGLT2 inhibitors may cost several hundred dollars a month but the exact prices will depend on your pharmacy and healthcare insurance coverage. Recently, out-of-pocket prices have come down, while advocates continue to work with policymakers to prioritize federal aid. If you struggle to afford SGLT2 inhibitors, speak with your pharmacist about pharmacy assistance programs. 

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