SGLT2 inhibitors

Treatments and therapies Medicines SGLT-2 inhibitors

Last Updated: December 06, 2024

Medically reviewed by NKF Patient Education Team

SGLT2 inhibitors are medicines that can help improve kidney and heart health for people living with CKD. They can also help people with type 2 diabetes manage their blood sugar. 

Table of Contents

About SGLT2 Inhibitors

SGLT2 inhibitors are a type of oral (taken by mouth) prescription medicine commonly recommended for people with chronic kidney disease (CKD). They help keep your glomeruli (small filters in your kidneys) healthy and lower your urine albumin-creatinine ratio (uACR) level (a marker of kidney damage). 

Most SGLT2 inhibitors have been shown in clinical trials to also help lower the risk of heart attack, stroke, and/or heart failure flare-ups. If you have type 2 diabetes, SGLT2 inhibitors can also help you manage your blood sugar levels.

Uses

Originally, SGLT2 inhibitors were developed to help people living with type 2 diabetes manage their blood glucose (sugar) levels. Later clinical trial data showed these medicines were also helpful for improving kidney and heart health for people with CKD and/or heart failure, even if they didn’t also have diabetes. These benefits are even stronger for people who also have albuminuria. SGLT2 inhibitors can also help people with other causes of CKD, including glomerular diseases like IgA nephropathy.

Some SGLT2 inhibitors are also FDA-approved to help manage blood sugar levels for children 10 years and older with type 2 diabetes. Studies are underway to see if SGLT2 inhibitors can be helpful for some kidney diseases in children who do not have diabetes.

How They Work

SGLT2 stands for “sodium-glucose co-transporter 2”. SGLT2 is like a control switch in your kidneys that helps keep glucose (sugar) and sodium (salt) in the body. Your body needs sugar for energy and sodium to prevent low blood pressure. So, SGLT2 tries to stop these items from leaving through your kidneys and urine. But too much of either can be a problem, leading to diabetes and high blood pressure. 

So, SGLT2 inhibitors help your kidneys remove the extra glucose (sugar) and sodium (salt) from your body through the urine (pee) to keep a healthy balance in your blood.

  • For people living with type 2 diabetes: helping your body remove extra sugar through your urine improves blood sugar levels. 
  • For people living with CKD (with or without diabetes): helping your body remove sugar and sodium through your urine also helps lower the pressure in your glomeruli (small filters in your kidneys). This helps keep your kidneys relaxed, which can help keep them healthy over the long-term. 

SGLT2 inhibitors also improve heart health, although it is not fully known exactly how they do. The leading research suggests it is likely also related to the lowering of pressure in the kidneys (glomeruli).

The kidney benefits of SGLT2 inhibitors are separate from their ability to lower blood sugar levels. So, even people with CKD who do not have diabetes may benefit from taking an SGLT2 inhibitor.

Types

SGLT2 inhibitors have generic names that end in “-flozin”. FDA-approved medicines in the class include: 

  • bexagliflozin (Brenzavvy)
  • canagliflozin (Invokana)
  • dapagliflozin (Farxiga)
  • empagliflozin (Jardiance)
  • ertugliflozin (Steglatro)

All these medicines work in relatively the same way and are taken orally (by mouth) once a day. 

Another medicine in this class is sotagliflozin (Inpefa). It is used in a slightly different way – to lower the risk of heart failure flare-ups and heart-related death in people with heart failure (or multiple risk factors for a heart failure flare-up). In addition to blocking SGLT2, it also blocks SGLT1 (which is mainly found in the small intestine) to lower the amount of sugar you absorb from food. Sotagliflozin is also taken orally (by mouth) once a day.

Effectiveness

SGLT2 inhibitors offer many health benefits including slowing the progression of CKD and lowering the risk of heart failure flare-ups and kidney failure. They also lower uACR levels for people with albuminuria.

For people living with type 2 diabetes, they also help improve blood glucose (sugar) and A1C levels. The effectiveness of SGLT2 inhibitors to lower blood sugar levels goes down as your estimated glomerular filtration rate (eGFR) goes down. However, the kidney and heart benefits remain, even in advanced stages of CKD. So, current guidelines recommend continuing to take these medications as long as they are not bothersome to you.

Some SGLT2 inhibitors have also been shown in clinical trials to lower the risk of dying from cardiovascular disease (heart attack or stroke) in people with CKD. 
 

Side Effects

Decreased eGFR


SGLT2 inhibitors are known to slightly lower the estimated glomerular filtration rate (eGFR), a measure of how well your kidneys work. This might seem strange since the medicines are supposed to help people living with kidney disease. 


In kidney disease, the kidneys are working under high stress. They work extra hard to keep filtering the blood. Unfortunately, this leads to faster “burnout” or damage to the glomeruli (small filters in the kidneys) and speeds up worsening kidney disease.


SGLT2 inhibitors lower the pressure in the kidneys. This gives the glomeruli (small filters in the kidneys) a chance to rest. In exchange, the eGFR goes down a little. This is not a sign of kidney disease getting worse. Over the long-term, people taking SGLT2 inhibitors have seen a much slower worsening of their CKD than people who are not taking them, despite the small decrease in eGFR when starting the medicine.

Increased urination (peeing more often)


SGLT2 inhibitors help your body get rid of extra glucose (sugar) and sodium (salt) through your urine. So, you may need to pee more often while taking an SGLT2 inhibitor. This side effect is usually more common in people with diabetes and when your blood sugar level is higher than your treatment target.


Taking your SGLT2 inhibitor in the morning can help lower the risk of needing to wake up at night to pee.

Urinary and genital infections


Higher levels of glucose (sugar) in the urine can increase the risk of infection in your genital area. This includes bacterial infections (often known as urinary tract infections or UTIs) and fungal infections (often known as yeast infections). SGLT2 inhibitors can also increase the infection risk in both men and women. This is another side effect that is usually more common in people with diabetes and when your blood sugar level is higher than your treatment target. 


Following proper genital hygiene like gently washing your genital area daily and wearing breathable (cotton) underwear can help lower your risk. If you have diabetes, keeping your blood sugar levels in your target range can also help lower your risk.

Low blood sugar (hypoglycemia)


SGLT2 inhibitors are not likely to cause low blood sugar by themselves. They only help your body get rid of extra sugar and don’t actively increase your insulin levels. So, this side effect is most likely in people with diabetes who are also taking insulin and/or a sulfonylurea (such as glipizide, glyburide, or glimepiride). 


Let your healthcare professional know right away if you are having low blood sugar events. The dose of your other diabetes medicine(s) may need to be lowered. 

Low blood pressure


SGLT2 inhibitors are not likely to lower your blood pressure by much. But if you have more frequent urination, this can lead to losing too much fluid which can cause low blood pressure. This side effect is more likely in people who have heart failure or take a diuretic (like furosemide, hydrochlorothiazide, or HCTZ). Low blood pressure symptoms include feeling weak, dizzy, or lightheaded, especially when standing up or changing positions.


If you have any of these symptoms, talk with your healthcare professional. The dose of your diuretic or other blood pressure medicine(s) may need to be lowered. 

Questions for Your Healthcare Team

  • Which side effects am I most likely to experience and how can I lower my risk?
    • SGLT2 inhibitors are used for many different health conditions and the level of risk for each side effect depends on which condition(s) you have and other factors. Knowing your personal level of risk can help you know what to expect.
  • Should any of my other medicines be changed or stopped when I start an SGLT2 inhibitor?
    • Depending on your situation, other medicines used for diabetes, high blood pressure, and/or heart failure may need to be switched to a lower dose or stopped when starting an SGLT2 inhibitor.
  • Should I temporarily stop taking my SGLT2 inhibitor before a planned surgery? If so, when should I stop it (and then when should I restart it)? 
    • SGLT2 inhibitors can increase the risk of ketoacidosis (high levels of acid in the blood) during surgery or prolonged fasting, especially in people with diabetes. Whether you need to stop taking your SGLT2 inhibitor before surgery depends on the type of surgery and your personal risk factors for ketoacidosis. When to stop the SGLT2 inhibitor will depend on which one you are taking.
  • What should I do if I develop a urinary tract infection (UTI) or yeast infection while taking this medication?
    • It is important to talk about your level of risk, know what to look for, and have a plan in place before something happens to help prevent any serious problems.

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This content is provided for informational use only and is not intended as medical advice or as a substitute for the medical advice of a healthcare professional.
© 2024 National Kidney Foundation, Inc.