SGLT2 Inhibitors: Why Do These Diabetes Pills Also Protect the Heart and Kidneys?
SGLT2 inhibitors are diabetes pills that make the kidneys pass extra glucose into the urine. In clinical trials, several of them also reduced heart failure hospitalizations and slowed kidney disease progression, including in some people without diabetes.
Written By: DocAi Health Editorial Team
Last Updated: 2026-09-21
SGLT2 inhibitors are diabetes pills that make the kidneys pass extra glucose into the urine. In clinical trials, several of them also reduced heart failure hospitalizations and slowed kidney disease progression, including in some people without diabetes. Several mechanisms probably contribute, and they are not fully understood. This article explains how these medicines work, who may benefit, common side effects, and the warning signs that need urgent care.
What SGLT2 inhibitors are and how they work
SGLT2 inhibitors (sodium-glucose cotransporter 2 inhibitors) are a class of oral medicines used for type 2 diabetes. Common examples include canagliflozin (Invokana), dapagliflozin (Farxiga), empagliflozin (Jardiance) and ertugliflozin (Steglatro). MedlinePlus has a general page on diabetes medicines that places them among the oral options.
Your kidneys filter blood all day and normally pull glucose back into the bloodstream. The SGLT2 protein in the kidney's filtering tubes does much of that work. These drugs block it, so more glucose leaves in the urine and blood sugar can fall. Because the effect does not depend on insulin, the pills can work alongside other diabetes treatments.
Blocking the protein also moves extra sodium and water into the urine, which may be one reason the drugs matter beyond blood sugar.
Why these diabetes pills may also protect the heart and kidneys
Outcome trials such as EMPA-REG OUTCOME, DAPA-HF and DAPA-CKD found fewer heart failure hospitalizations and slower kidney function decline in many participants. Later trials suggested similar benefits in people with heart failure or chronic kidney disease who did not have diabetes. Because of this, these drugs are now used for heart and kidney reasons as well as for glucose.
Researchers do not fully agree on why. Several factors are thought to contribute:
- Less fluid and sodium load. The mild diuretic effect may reduce strain on a weakened heart.
- Changes inside the kidney. Blocking glucose and sodium reabsorption may lower pressure inside the kidney's filters, which could reduce long-term damage. Reviews of diabetic kidney disease discuss this idea.
- Metabolic effects. Modest weight loss and small drops in blood pressure may help.
- Other effects. Possible changes in inflammation and in how the heart uses energy are still being studied.
No single explanation accounts for the whole benefit, and the benefit does not simply track how much a drug lowers A1C.
Who may be offered an SGLT2 inhibitor
Current diabetes care guidance generally supports considering one for adults with type 2 diabetes and heart failure, established cardiovascular disease, or chronic kidney disease, depending on kidney function and other factors. Some people with heart failure or kidney disease take one even without diabetes. The decision depends on your kidney function, other medicines, and your risks, so it is individual.
If you are comparing options, metformin remains a common first medicine and has its own page: Metformin: Uses, Side Effects, and What to Know. Injectable options are covered in the GLP-1 article linked below the FAQ.
Glucose-lowering by these pills can fade as kidney function declines, but heart and kidney benefits may persist. Your clinician checks kidney function before and during treatment to decide whether the medicine remains appropriate.
Common side effects of SGLT2 inhibitors
Genital yeast infections and urinary infections
Extra sugar in the urine can feed yeast and bacteria. Genital yeast infections (itching, redness, discharge, or a rash on the penis or vulva) are a recognized side effect, and urinary tract infections can occur. Careful washing and drying may help, and most yeast infections can be treated. Tell your clinician about symptoms so they can decide on treatment and whether to continue the drug.
Dehydration, dizziness and low blood pressure
Because the drugs increase urine output, some people feel lightheaded when standing, especially if they also take a water pill or blood pressure medicine, are older, or are ill with vomiting or diarrhea. If you have fainting spells, see the article on fainting in an older adult. Our page on how water pills work explains the overlap with diuretics.
More frequent urination and thirst
Passing more urine is expected. Some people also notice a dry mouth; MedlinePlus has general tips on dry mouth.
Low blood sugar
SGLT2 inhibitors alone carry a low risk of low blood sugar, but the risk can rise when they are combined with insulin or a sulfonylurea. Your prescriber may adjust those other medicines. Do not change or stop any dose on your own, with one exception: during illness with vomiting, diarrhea or not eating and drinking, or before surgery or a fasting procedure, follow your sick-day plan or call your prescriber the same day, because pausing the SGLT2 inhibitor is usually advised in those situations. Do not stop other diabetes medicines such as insulin unless your prescriber tells you to. Ask for sick-day instructions in advance.
Serious but uncommon risks to know about
Ketoacidosis, including with normal blood sugar
Diabetic ketoacidosis (DKA) happens when the body burns fat for fuel and acids called ketones build up. With SGLT2 inhibitors it can occur even when blood glucose is only mildly raised or normal, so a normal reading may not be reassuring. Risk factors can include illness, vomiting, reduced eating, heavy alcohol use, surgery, and insulin deficiency. The prescribing information for this class carries a warning about ketoacidosis. Nausea, vomiting, abdominal pain, unusual tiredness, and fast or labored breathing need emergency evaluation.
Medication labeling for this class advises that the drug be held during acute illness with vomiting, diarrhea or poor intake, and before scheduled surgery, because continuing can raise the risk of ketoacidosis and dehydration-related kidney injury. Your prescriber confirms when to do so. See the sick-day section below.
Serious genital and perineal infection
A rare but serious infection of the tissue around the genitals and perineum (necrotizing fasciitis of the perineum, sometimes called Fournier gangrene) has been reported with this drug class. It is much less common than ordinary yeast infections. Pain, tenderness, redness or swelling of the genitals or the area behind them, together with fever or feeling very unwell, needs emergency care.
Amputation and fractures
A boxed warning for amputation was once attached to canagliflozin, based on a trial signal, and was later removed from the labeling after further data, though foot care remains important. Tell your clinician about foot sores, pain or skin changes, particularly if you already have nerve or circulation problems from diabetes.
Kidney function and pregnancy
A small dip in estimated kidney function is often seen early after starting, and your clinician may recheck blood tests. These drugs are generally not recommended in pregnancy. See the gestational diabetes article for pregnancy-related diabetes care. Using an SGLT2 inhibitor in people with type 1 diabetes is not an approved use and carries a higher ketoacidosis risk.
Sick days and procedures: when the medicine may be paused
If you are vomiting, have diarrhea, or cannot eat or drink normally, call your prescriber the same day or follow the sick-day plan you were given. Pausing the SGLT2 inhibitor is usually advised in this situation, and your prescriber will tell you when to restart it. If you also have belly pain, fast or deep breathing or marked drowsiness, go to the emergency room. Ask for these instructions in advance rather than waiting until you feel unwell.
Tell any surgeon or proceduralist that you take an SGLT2 inhibitor. Drug labeling for these medicines has advised stopping canagliflozin, dapagliflozin and empagliflozin at least 3 days, and ertugliflozin at least 4 days, before scheduled surgery; your surgical team or prescriber will confirm the timing for you and your drug, including for a procedure that requires fasting. Keep up any home monitoring a clinician has recommended, including blood glucose checks, and ask whether ketone testing is appropriate for you.
Other points to mention at appointments:
- All prescription, over-the-counter and herbal products, including diuretics and NSAIDs, which can also affect the kidneys (see the article on NSAIDs and kidney health).
- Any history of pancreatitis, frequent urinary or genital infections, or heavy alcohol use.
- Plans for pregnancy or breastfeeding.
How these medicines fit with other diabetes care
An SGLT2 inhibitor is one part of a plan that also includes food choices, activity, blood pressure and cholesterol management, and regular kidney and eye checks. Blood sugar goals differ by person; the page on A1C goals for older adults covers that topic. Insulin, discussed on our insulin therapy page, may still be needed for some people. Heart failure care is described in the heart failure stages article, and the BNP article explains one common blood test. Read the medication guide that comes with your prescription and ask your pharmacist if anything is unclear.
When to Seek Medical Care
When to Seek Urgent or Emergency Care
Most people tolerate SGLT2 inhibitors well, but a few uncommon complications can progress quickly and need emergency evaluation. If you take one of these medicines and have any of the problems below, get help right away and tell the team which drug you take. This guidance is in addition to, not a replacement for, the general disclaimer above.
Emergency, call 911 or go to the emergency room immediately if:
- Persistent vomiting with belly pain, fast or deep labored breathing, and unusual drowsiness or confusion, which may be ketoacidosis even if your blood sugar reading looks normal.
- Severe pain, swelling or redness of the genitals or the skin between the genitals and anus, especially with fever or feeling very ill, which may be a serious tissue infection.
- Fainting or collapse, or confusion with a racing heart, after vomiting, diarrhea or heavy fluid loss that you cannot correct.
- Signs of a stroke such as facial drooping, arm weakness or trouble speaking, or chest pressure or pain that spreads to the arm or jaw or comes with shortness of breath, sweating or fainting.
- Swelling of the lips, face or throat, or trouble breathing, which can signal a serious allergic reaction to the medicine.
See a doctor soon (same-day or next available appointment) if:
- Genital itching, redness, discharge or rash that does not improve, so your clinician can decide on treatment and whether to continue the medicine.
- Burning with urination, pelvic or flank pain, or fever, which may be a urinary tract infection needing prompt evaluation.
- Lightheadedness when standing, very dark urine or marked thirst, which can suggest dehydration, particularly if you also take a diuretic.
- A new foot sore, blister, color change or pain in the leg or foot, especially if you have diabetic nerve or circulation problems.
- Vomiting, diarrhea or not eating and drinking normally: follow your sick-day plan or call your prescriber the same day, since pausing the SGLT2 inhibitor is usually advised, and go to the emergency room if belly pain, fast or deep breathing or marked drowsiness develops. Before planned surgery or a fasting procedure, your surgical team or prescriber will confirm the timing.
Frequently Asked Questions
How do SGLT2 inhibitors lower blood sugar?
They block a protein in the kidney that normally returns filtered glucose to the blood. With that protein blocked, extra glucose leaves in the urine and blood sugar can fall. The effect does not rely on insulin, so these pills can be combined with other diabetes medicines. The glucose-lowering effect tends to be smaller when kidney function is reduced.
Can I take an SGLT2 inhibitor if I do not have diabetes?
Some people with heart failure or chronic kidney disease are prescribed certain SGLT2 inhibitors even without diabetes, because trials suggested heart and kidney benefits in these groups. Whether it is appropriate depends on your diagnosis, kidney function and other medicines. Only a prescriber who knows your history can decide, so do not use another person's supply.
Why do SGLT2 inhibitors cause yeast infections?
Glucose in the urine can create a warm, sugar-rich environment where yeast grows, especially around the genitals. Many infections are mild and treatable. Keeping the area clean and dry may help. Tell your clinician if itching, redness or discharge develops, because they can decide on treatment and whether the medicine should continue.
Can an SGLT2 inhibitor cause ketoacidosis with normal blood sugar?
Yes, it can occur even when blood glucose is not very high, which is why the prescribing information for this class carries a ketoacidosis warning. Nausea, vomiting, belly pain, unusual tiredness or fast breathing need emergency evaluation. Tell every clinician you take the medicine, particularly before surgery or when you are ill and not eating.
Should I stop my SGLT2 inhibitor when I am sick?
Do not decide on your own. If you are vomiting, have diarrhea, or cannot eat or drink normally, call your prescriber the same day. Your prescriber will tell you whether to pause the medicine and when to restart it, because continuing can raise the risk of ketoacidosis and kidney injury from dehydration. Ask for a written sick-day plan ahead of time.
Do SGLT2 inhibitors cause weight loss?
Many people lose a modest amount of weight, partly from calories passed as glucose in the urine and partly from fluid loss. The change varies and is generally smaller than with injectable GLP-1 medicines. Weight is not the main reason these drugs are prescribed, and results differ from person to person.
Are SGLT2 inhibitors safe for people with kidney disease?
Several are used in chronic kidney disease because trials suggested slower decline in kidney function. A small early drop in filtering numbers is often seen and may not signal harm. Each drug has kidney-function limits in its label, so your clinician checks blood tests before and during treatment to see whether continuing makes sense for you.
Can older adults take SGLT2 inhibitors?
Older adults can take them, and many have heart or kidney conditions where the benefit may matter. They may be more prone to dehydration, dizziness and falls, especially with water pills or blood pressure medicines. Tell your clinician about any lightheadedness or fainting so they can review your whole medication list.
Related articles
Metformin: Uses, Side Effects, and What to KnowWhat Side Effects Are Common With GLP-1 Diabetes and Weight-Loss Injections?Insulin Therapy: Types, Dosing Safety, Storage and Side EffectsSources
- MedlinePlus (NIH) - Diabetes Medicines
- MedlinePlus (NIH) - Diabetes Type 2
- MedlinePlus (NIH) - Dry Mouth
- PubMed Central (NIH) - New Approaches to Diabetic Nephropathy from Bed to Bench
- PubMed Central (NIH) - Diabetes and treatment of chronic heart failure in a large real-world heart failure population