- 1 Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a newer class of Type 2 diabetes medication that work by stopping glucose from being reabsorbed into the blood. But the FDA warned that these drugs can also cause ketoacidosis, a condition that requires hospitalization and can cause fatal swelling of the brain, severe dehydration and coma.
- 2 What Are SGLT2 Inhibitors?
- 3 Farxiga
- 4 Invokana
- 5 Jardiance
- 6 Serious Ketoacidosis Side Effects
- 7 Cases of Diabetic Ketoacidosis
- 8 Other Serious Side Effects of SGLT2 Inhibitors
- 9 Common Side Effects
- 10 Drug Interactions and Pregnancy Risk
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a newer class of Type 2 diabetes medication that work by stopping glucose from being reabsorbed into the blood. But the FDA warned that these drugs can also cause ketoacidosis, a condition that requires hospitalization and can cause fatal swelling of the brain, severe dehydration and coma.
The body produces extra insulin to make up for the insulin resistance. Over time, it’s no longer able to produce the extra insulin to keep glucose levels normal.
According to the American Diabetes Association (ADA), 29.1 million Americans – or 9.3 percent of the U.S. population – had diabetes in 2012. To combat this growing health issue, many medications came to the market to help with glucose control. Glucose control refers to keeping blood sugars at a normal level determined by the person’s physician.
The U.S. Food & Drug Administration (FDA), in March 2013 approved Invokana (canaglifozin) for the use by individuals with diabetes. The manufacturers of canaglifozin, Johnson & Johnson, claimed it would improve glucose control in adults with Type 2 Diabetes. The drug was a new class of diabetes called sodium-glucose co-transporter 2, or SGLT2.
Other SGLT2 inhibitors that joined canaglifozin on the market to help with glucose control included:
- Farxiga, also called dapagliflozin, approved January 2014.
- Jardiance, also called empagliflozin, approved August 2014. The manufacturer of empagliflozin claimed it improved hemoglobin A1c levels.
In 2015, the FDA announced a warning about SGLT2 inhibitors for diabetes. This drug would cause a serious medical condition in those who took it. The new information about SGLT2 inhibitors may generate a lot of lawsuits by patients taking the drug.
What Are SGLT2 Inhibitors?
Manufacturers claimed the SGLT2 would work in conjunction of exercise, other medications and diet. The other medications mentioned include common diabetes 2 treatments such as insulin, metformin, pioglitazone and sulfonylurea.
Although the FDA approved SGLT2, it required Johnson & Johnson to conduct post-marketing students using canaglifozin. The studied proposed included:
- An advanced pharmacovigilance program to monitor for malignancies, photosensitivity, hypersensitive reactions and serious bouts of pancreatitis
- Cardiovascular clinical trials
- Bone study
- How the medication would adversely affect pregnancies
One of the major reasons diabetics have glucose control problems is because a person’s kidneys temporarily filters the glucose from the bloodstream. Unfortunately, the glucose is reabsorbed into the bloodstream. Traditional diabetes drugs try to improve glucose control by targeting the pancreas and liver to do three things:
- Reduce insulin resistance
- Improve a person’s insulin sensitivity
- Improve insulin secretion
SGLT2 inhibitors work differently. The inhibitors don’t work on insulin production. Instead, they target a person’s kidneys. The inhibitors work to reduce sugar levels in the blood by increasing sugar excretion and stopping the kidneys from reabsorbing the sugar. The process allows a lot of the glucose in the body to leave via the urine. In other words, the inhibitors acted like a diuretic.
Farxiga (dapagliflozin) is a pill that patients take once daily with food. The drug was finally approved in 2014 after the FDA previously rejected it because of bladder cancer concerns. It is not for treatment of type 1 diabetes mellitus or for use in people with diabetic ketoacidosis.
FDA studies of this drug, manufactured and marketed by Bristol-Meyers Squibb Co. and AstraZeneca, revealed that people who take it are five times more likely to develop bladder cancer. In addition, research shows that the drug also could promote a faster progression of bladder cancer in people who are already prone to the disease. So, people with bladder cancer should not take this drug.
Farxiga’s side effects include urinary tract infections (UTIs) and genital fungal infections. In addition, the medication insert also warns about low blood pressure. People with kidney problems are more prone to suffer from this side effect. This medication may also cause kidney problems.
The FDA approved Invokana (canagliflozin), manufactured by Johnson & Johnson’s Janssen Pharmaceuticals, in 2013. The drug is not intended to treat Type 1 diabetes and shouldn’t be used in people with diabetic ketoacidosis.
Some of the most common side effects people reported when taking the drug include: increased urination, genital myotic infections and urinary tract infections. People with kidney disease or impaired kidneys should not take this medication.
In clinical studies, Invokana also increased cholesterol levels in the blood. In animal studies, the drug caused an increase in tumor development of some cancers in rats.
Jardiance (empagliflozin) is an oral medication marketed and sold by Boehringer Ingelheim and was approved in 2014. Like other SGLT2 inhibitors, this drug is not intended to treat Type 1 diabetes and shouldn’t be used in people with diabetic ketoacidosis.
One of the most common side effects of Jardiance is urinary tract infection. Some other troublesome problems reported in people who take this medication include male and female yeast infections, dehydration and hypoglycemia (low blood sugar). This drug also increases the amount of fat in the blood.
In animal studies, the drug caused increased incidence of kidney and lymph node tumors in rats. At higher doses, the drug caused birth defects in rabbit fetuses.
Serious Ketoacidosis Side Effects
The FDA warned in May 2015 that SGLT2 inhibitors causes a serious condition called diabetic ketoacidosis. Diabetic ketoacidosis causes high levels ketones, or blood acids, which are poisonous. The condition occurs when the body loses its ability to produce enough needed insulin.
Without enough insulin, a person’s body begins to use fat as a fuel source as an alternative. As the body breaks down fat for fuel, it also builds up toxic acids in the bloodstream. The symptoms and signs of diabetic ketoacidosis develops quickly. Typically, within 24 hours of the start of breaking down fat for energy.
Symptoms of diabetic ketoacidosis include:
- Frequent urination
- Excessive thirst
- Abdominal pain
- Vomiting and nausea
- Shortness of breath
- Fruity-scented breath
Possible complications of diabetic ketoacidosis includes:
- Low potassium
- Low blood sugar
- Swelling in the brain
If left untreated, diabetic ketoacidosis is fatal. Diabetic ketoacidosis is usually a medical emergency. It is vital to seek immediate treatment when experiencing symptoms such as:
- Fruity breath
- Decreased consciousness
- Trouble breathing
Cases of Diabetic Ketoacidosis
The FDA identified about 20 cases of diabetic ketoacidosis in patients taking SGLT2 inhibitors. The 20 cases occurred from March 2013 to June 2014. The individuals required treatment in an emergency room or hospital for diabetic ketoacidosis.
Diabetic ketoacidosis is often the first sign someone undiagnosed with type 1 diabetes. It is also a condition anyone with Type 1 diabetes must watch out for any time he misses an insulin shot, has an infection or becomes ill.
Diabetic ketoacidosis isn’t common in those with Type 2 diabetes. Thus, type 2 diabetics may not be aware of the signs and symptoms of diabetic ketoacidosis.
Other Serious Side Effects of SGLT2 Inhibitors
The potential benefit of SGLT2 inhibitors was its ability to dump glucose into the urine which helped with glucose control. However, two separate studies show the drugs also increase endogenous glucose and hormone glucagon levels.
Glucose comes from two sources: endogenous and exogenous sources. Exogenous glucose comes from food. Endogenous glucose comes from the liver. The liver breaks down stored starches and supplies the body with the glucose it’s in a fasted state.
The SGLT2 inhibitors do what they are designed to do. They increase renal glucose excretion in the urine and lowers fasting plasma glucose. It also increases endogenous glucose production and glucagon levels.
Unfortunately, the increase in endogenous glucose production offsets about half of the glucose dumping. In other words, the drugs decrease the sugar in the bloodstream by dumping into the urine. At the same time, it creases the two sources of glucose which negates the glucose control benefit. So an individual still has too much glucose in his body.
Common Side Effects
Some people who have hypertension may experience benefits like lower blood pressure. Other individuals may experience adverse reactions like dizziness, lightheadedness or fainting.
Common side effects of SGLT2 include the genital yeast infections, dehydration and urinary tract infections. It may also increase levels of bad cholesterol called LDL.
The FDA reviewer found Johnson & Johnson’s canagliflozin SGLT2 inhibitor increased the risk of heart attack in diabetics taking the drug. Data revealed canagliflozin raised the risk of LDL cholesterol.
Drug Interactions and Pregnancy Risk
SGLT2 inhibitors may affect the renal development of a fetus if taken while a woman is pregnant. It is also not recommended for a woman who is breast feeding because it’s not known if the drug is distributed to the baby via breast milk. Therefore, they aren’t for women who are pregnant, planning to become pregnant or breastfeeding.