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SGLT2 inhibitors work by acting on the kidneys. SGLT2 inhibitors have also been linked with multiple kidney-related problems such as renal impairment and acute kidney injury. Serious urinary tract infections that can affect the kidneys, known as pyelonephritis, or cause blood infections, known as urosepsis, are also potential side effects.
Brand names of SGLT2 inhibitors include Invokana, Invokamet, Farxiga, Glyxambi, Jardiance, Xigduo XR and Synjardy. Each of these medications has been associated with health risks. Some people who have suffered the side effects of SGLT2 inhibitors have sought legal compensation.
As well as causing problems with kidneys, the U.S. Food and Drug Administration (FDA) warned in a May 2015 Safety Announcement that SGLT2 inhibitors may result in a serious condition known as diabetic ketoacidosis. Usually, this condition can occur when a diabetic’s blood-sugar levels dip below a normal range, indicating that the body does not have enough glucose (or blood sugar), the body’s preferred sustenance.
When the body lacks glucose, the body instead uses fat for fuel. The process of burning fat to fuel the body can produce a large amount of ketones, which are blood acids that can poison the body in excessive amounts. This state of excessive ketones in the body is diabetic ketoacidosis.
When diabetic ketoacidosis occurs, the sufferer can fall into a diabetic coma. The effects of ketoacidosis can be lethal if the condition is not promptly addressed. The FDA has advised that patients should “stop taking their SGLT2 inhibitor and seek medical attention immediately if they have any symptoms of ketoacidosis. …” Treatment of ketoacidosis usually requires hospitalization.
Normally, diabetic ketoacidosis is brought on by a severe imbalance of dietary glucose. However, the FDA found that many of the reported SGLT2 inhibitor-related cases of ketoacidosis occurred in patients who were euglycemic (which means they had normal blood sugar levels) or had only slightly elevated blood sugar levels at the time of their ketoacidosis.
In addition to the FDA’s findings, medical literature has also described similar development of diabetic ketoacidosis in patients taking SGLT2 inhibitors. Several studies have reported on euglycemic ketoacidosis as a potential side effect of taking the SGLT2 inhibitor canagliflozin (Invokana).
A recently published case series described nine instances wherein patients, seven with Type 1 diabetes and two with Type 2 diabetes, developed diabetic ketoacidosis after taking the same SGLT2 inhibitor drug. Three patients developed ketoacidosis for a second time after stopping and restarting the medication. Much like the cases described in the FDA’s Safety Announcement, several patients had normal or near-normal blood sugar levels, unlike what is typically observed with diabetic ketoacidosis cases.
Signs of Diabetic ketoacidosis
Diabetic ketoacidosis signs and symptoms may include:
Unusual fatigue or sleepiness
In addition to SGLT2 inhibitor use, other risk factors for diabetic ketoacidosis may include:
- Recent Surgery
- Physical trauma
- Mental distress
- Blockage in a heart artery
- Uncontrolled insulin
Serious Urinary Tract Infections Resulting in Blood or Kidney Infections
Also contained in the FDA Safety Announcement in December 2015 is a warning that SGLT2 inhibitors can cause serious urinary tract infections.
The urinary tract can become infected at multiple locations, affecting the bladder, the kidneys (where blood is filtered and urine is created), the ureters (which take urine from the kidneys to the bladder), or the urethra, which is the tube through which urine travels out of the bladder to be excreted from the body. A urinary tract infection (UTI) occurs when any of these areas becomes infected.
The side effects of UTIs are often so uncomfortable that many people see their doctor for a stronger, prescription treatment, such as an antibiotic.
Most times, a UTI is caused by the presence of bacteria that travels into the bladder via the urethra. However, UTIs caused by SGLT2 inhibitors may form differently. When glucose is ingested, the body filters it through the kidneys, which reabsorb some of the glucose. For people with diabetes, holding onto this additional sugar can be problematic. To combat this reuptake of sugar, SGLT2 inhibitors prevent the kidneys from retaining that extra sugar, instead taking the extra sugar out of the body via urine. This effect can increase the concentration of urinary glucose, potentially creating a more favorable environment for bacterial growth that can cause UTIs.
Symptoms of urinary tract infections may include:
- A burning sensation during urination
- Frequent urination
- Feeling of urgent need to urinate
- Pelvic pain
- Blood in the urine
- Back pain
- Nausea or vomiting
Though SGLT2 inhibitor use has been linked to the development of UTIs, several additional risk factors include:
- Being female
- Sexual activity
- Kidney stones
- Weak immune system
- Prior kidney transplant
- Antibiotic use
- Enlarged prostate