SGLT2 Inhibitors

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are oral medications that the U.S. Food and Drug Administration (FDA) has approved for Type 2 diabetes and, in some cases, chronic kidney disease (CKD) and heart failure. They work by helping the body eliminate excess glucose and sodium through urination.

If you’re not sure if your medication is an SGLT2 inhibitor, look for a generic name ending in “-flozin.”

Not all SGLT2 inhibitors are approved for all the same conditions. The FDA may approve some of these drugs for different applications.

How SGLT2 Inhibitors Work

SGLT2 inhibitors prevent the kidneys from absorbing too much sodium and glucose. The specific protein these drugs inhibit is known as sodium-glucose cotransporter 2 (SGLT2), which explains the name of this drug class.

When SGLT2 inhibitors block this protein, the body eliminates some excess sugar and salt through urine. This lowers blood sugar levels for people with Type 2 diabetes and relaxes the kidneys for those with chronic kidney disease. This process can help reduce blood pressure and even result in some weight loss.

Studies indicate that kidney relaxation may also improve heart health, though the exact way SGLT2 inhibitors affect the heart isn’t fully understood.

SGLT2 inhibitors help balance sodium and glucose levels in the blood, leading the FDA to approve them as treatments for Type 2 diabetes, CKD and heart failure. However, like all medicines, they come with some risks. If you are considering SGLT2 inhibitors, it’s essential to understand the key benefits, possible side effects and how to weigh the pros and cons with your doctor.

Benefits of SGLT2 Inhibitors

SGLT2 inhibitors are best known as a Type 2 diabetes treatment, but they’re also FDA-approved for heart failure and CKD.

Risks and Side Effects of SGLT2 Inhibitors

While SGLT2 inhibitors offer significant benefits, they have side effects and risks.

Common side effects of SGLT2 inhibitors can include more frequent urination, low blood sugar, low blood pressure and urinary and genital infections. People with CKD may also see a short-lived decrease in kidney function while the body adjusts.

More rarely, people taking SGLT2 inhibitors experience significant health challenges. Key risks include diabetic ketoacidosis and lower limb amputations.

Fungal Infections and Fournier’s Gangrene

In August 2018, the FDA released a Drug Safety Communication warning that SGLT2 inhibitors may cause a rare but serious genital infection called necrotizing fasciitis of the perineum, also known as Fournier’s gangrene. The disease can be life-threatening. Symptoms include tenderness, fever and redness or swelling of the genitals.

In general, about 1.6 in 100,000 men get Fournier’s gangrene each year in the United States. The FDA estimated that about 1.7 million people received a prescription for an SGLT2 inhibitor in 2017.

The FDA reported it found 12 cases of Fournier’s gangrene in people who took an SGLT2 inhibitor from March 2013 to May 2018. All seven men and five women ended up in the hospital and required surgery.

“Fournier’s gangrene developed within several months of the patients starting an SGLT2 inhibitor, and the drug was stopped in most cases,” the FDA said. “Some patients required multiple disfiguring surgeries, some developed complications and one patient died.”

Conversely, the FDA only identified six Fournier’s gangrene cases in people who took other diabetes drugs during a period of over 30 years.

In their 2017 article in the journal Diabetic Medicine, Dr. Shanal Kumar and colleagues described the case of a 41-year-old man with Type 2 diabetes who developed Fournier’s gangrene after taking empagliflozin and metformin. He had a swollen scrotum and inflammation.

Doctors stopped treating the man with empagliflozin. They performed emergency surgery to wash out the infection and gave him a skin graft to replace damaged skin. For two weeks, he received intravenous antibiotics in the hospital, followed by oral antibiotics at home.

“There is a wide clinical spectrum of genital infections associated with SGLT2 inhibitors, with most being generally mild and easily treated,” the authors concluded. “However, risk factors such as diabetes, obesity, immunosuppressed states, smoking, alcohol abuse and end-stage renal or liver failure may increase the risk of potentially more severe infections such as Fournier’s gangrene.”

Ketoacidosis and Urinary Tract Infections

In 2015, the FDA released a Drug Safety Communication warning about the risk of ketoacidosis — also called diabetic ketoacidosis — and serious urinary tract infections (UTIs). The agency required drug companies to add warnings to SGLT2 inhibitor medication labels.

Normally, the FDA advises against stopping medications without consulting a doctor. However, the agency said in its communication that patients should stop taking their SGLT2 inhibitor immediately and seek medical attention if they suffer symptoms of ketoacidosis, including trouble breathing, nausea, vomiting, abdominal pain and tiredness.

People who think they may have a urinary tract infection don’t need to stop taking their medication immediately, but should talk to their doctors right away.

At the time, the agency released the warning for ketoacidosis after it identified 73 cases in the FDA Adverse Event Reporting System (FAERS) from March 2013 to May 2015. All patients required hospitalization or emergency department visits. Those numbers have since increased. As of November 2025, there were 6,834 diabetic ketoacidosis cases in FAERS reported by users of Farxiga, Invokana, Jardiance, and Steglatro.

In the same communication, the FDA warned about the risk of urinary tract infections that could turn into life-threatening blood infections (urosepsis) and kidney infections (pyelonephritis). The agency identified 19 cases of blood and kidney infections that began as urinary tract infections, all of which required hospitalization.

Invokana Amputations

In 2017, the FDA required Johnson & Johnson to add a black box warning to Invokana and two other canagliflozin drugs, Invokament and Invokamet XR, for lower limb amputations. The agency based its decision on the results of two large, randomized, placebo-controlled trials that found amputations occurred roughly twice as often in people who took canagliflozin versus a placebo, according to the FDA’s Drug Safety Communication.

Amputation of the toe and mid-foot were most common, but amputations of the leg above and below the knee also occurred. Some people had amputations on both legs.

The FDA urged patients with the following symptoms to contact their doctors:

• Infections
• Leg or foot pain or tenderness
• Sores or ulcers

As of November 2025, the FDA had received 4,092 reports of toe, leg and foot amputations among people taking Invokana.

While the FDA found evidence of amputations connected to Invokana, a study by Johnson & Johnson showed no increased amputation risk compared to other diabetes drugs. Patrick B. Ryan of Janssen Research & Development and colleagues published the findings of the OBSERVE-4D study in the journal Diabetes, Obesity & Metabolism.

In August 2020, the FDA reviewed evidence from three new clinical trials and removed the amputation black box warning but retained a precaution about amputations in the “Warnings and Precautions” section. In its statement, the agency said that “newly identified effects of canagliflozin” for heart and kidney issues indicated that the medication was more beneficial than previously realized. In addition, the FDA stated that safety data from recent trials suggested a lower, although still increased, risk of amputation.

Risk-Benefit Considerations of SGLT2 Inhibitors

As with any medication, discussing SGLT2 inhibitors with your doctor before taking them is essential. These medications can help those with diabetes, CKD and heart failure. However, there are rare, serious side effects. For instance, Invokana may increase the risk of amputations, and canagliflozin can elevate the chance of diabetic ketoacidosis (DKA).

However, the benefits usually outweigh the risks, especially with regular monitoring by your health care provider.

According to the National Kidney Foundation, SGLT2 inhibitors may initially cause a slight decrease in kidney function, but this is a normal response. The medicine lowers pressure in the kidneys, giving them a break. Over time, this helps protect the kidneys and slows down damage, even though the first change in test results might seem concerning.

The FDA has carefully monitored SGLT2 inhibitors for safety. The agency has added significant warnings and updates to the drugs’ labels.

Though the medications are part of the same drug class, the warnings can vary by brand.

Drugwatch is not currently aware of any attorneys accepting SGLT2 inhibitor lawsuits. However, more than 1,200 people filed SGLT2 inhibitor lawsuits in the 2010s.

The U.S. Judicial Panel on Multidistrict Litigation combined multiple SGLT2 inhibitor lawsuits into two multidistrict litigations (MDLs). An MDL allows the panel to consolidate several similar lawsuits into one litigation in a single federal court, simplifying the legal process. One MDL included cases about Invokana, while the other consolidated Farxiga lawsuits.

The judge in the Farxiga MDL closed 67 cases in 2020, returning one remaining case to the court where attorneys initially filed it. The judge presiding over the Invokana MDL closed the litigation in 2023 after attorneys for both sides resolved more than 1,200 lawsuits.

If you suspect that you or someone you know is experiencing problems from SGLT2 inhibitors, act promptly to minimize risks and support public health.

Seek immediate medical attention if you have signs of infection or DKA, as delays can lead to serious issues. Report any side effects, even if you’re unsure of the cause, as documentation can aid in wider medical and legal matters.

When To Seek Immediate Medical Attention

You should contact your health care provider immediately if you experience symptoms of severe SGLT2 inhibitor side effects such as DKA, Fournier’s gangrene, other severe infections, limb pain or ulcers.

Consult your doctor before stopping treatment and let them know immediately if you experience any of these symptoms while taking an SGLT2 inhibitor.

You should have regular checkups to monitor your health while on an SGLT2 inhibitor and contact your provider if you have questions or concerns.

Report Severe Side Effects To the FDA

To submit a report, use the FDA MedWatch portal online or call 1-888-INFO-FDA (1-888-463-6332) for a reporting form. Your submission should include your demographics (age, sex, medical condition, etc.), medication, dosage and duration. You should also include a description of the adverse event and any outcomes.

Reporting is vital, as the FDA uses this information to update safety warnings and inform prescribing guidelines through post-market surveillance.

Document Your Injuries for Long-Term Protection

It’s essential to keep a record of your symptoms. Create a journal where you record the date each symptom began, its severity and how it progressed over time. Make sure to write down any medications you were taking and their dosages, as well as details about doctor visits and treatments you received.

This can help your doctor understand what’s happening and plan the best treatment.

It’s also a good idea to get copies of your medical records. This includes essential lab results, such as blood sugar levels and scans related to your health issues. This information can be invaluable if you must report a problem to health authorities or are considering legal action.