Type 2 Diabetes Drugs: SGLT2 Inhibitor Antidiabetics
Type 2 sodium-glucose co-transporter (SGLT2) inhibitors are newer medications used to treat Type 2 diabetes. The SGLT2 inhibitor class of antidiabetic medications is also sometimes known as the “gliflozins” and includes the medications:
- Invokana (canagliflozin) – manufactured by Janssen, a division of Johnson & Johnson
- Jardiance (empagliflozin) – manufactured by Boehringer Ingelheim, co-marketed by Lilly
- Farxiga (dapagliflozin) – co-marketed in Europe and the U.S by Bristol-Myers Squibb and AstraZeneca
Two of these medications are also available in combination form with another antidiabetic medication, metformin and sold under the brand names Invokamet (canagliflozin / metformin) and Xigduo XR (dapagliflozin / metformin. Boehringer Ingelheim has also applied for approval of a metformin combination of Jardiance and approval is expected later this year.
Johnson & Johnson, based in New Jersey, is the largest pharmaceutical company in the U.S. with estimated annual sales of over $72 billion. AstraZeneca is based in London and has annual sales of over $26 billion and Bristol-Myers Squibb is based in New York with annual revenue of $20 billion. Boehringer Ingelheim is based in Ingelheim, Germany and has annual sales of $15 billion and its co-marketer, Indiana-based Eli Lilly has annual revenue of $20 billion.
About Type 2 Diabetes
Diabetes is a medical condition in which the body does not process sugar correctly. Over time excessive glucose levels in the blood stream may damage organs such as the eyes, kidney and skin, resulting in blindness, kidney failure and the necessity for amputation of the feet and legs.
Type 2 diabetes is the most common and affects up to 28 million Americans. It is often related to obesity and may contribute to a number of additional disease including hypertension, high cholesterol levels and cardiovascular death.
In normal people, insulin helps to transport glucose or sugar from the blood stream into the cells, where it can be used as energy. Type 2 diabetics may not produce enough insulin, or the blood cells may have become resistant to insulin – leaving much of the sugar in the bloodstream.
Antidiabetic medication has traditionally worked by increasing the production of insulin, increasing the body’s sensitivity to insulin or by preventing insulin from being absorbed in the intestines. As newer medications, SGLT2 inhibitors antidiabetics work differently from other antidiabetic medications and were hoped to help thousands of patients who failed to respond adequately to other medications, unfortunately the medications may be harming some patients instead of helping them.
SLGT2 Inhibitor Actions
When the kidneys work normally in a non-diabetic patients, extra glucose in the blood stream is filtered from the blood and reabsorbed back into the bloodstream by the kidney “tubules” where it can be used as energy.
As type 2 diabetics have too much glucose in the blood, SGLT2 inhibitors prevent the kidneys from reabsorbing that glucose so that it is passed out of the body in the urine. SGLT2 inhibitors result in over 100 grams of sugar being excreted into the urine, which is the same as excreting over 400 calories, causing some people to lose weight.
All medications have side effects, most of which are mild to moderate. The SGLT2 inhibitors have a number of common side effects which can be bothersome but are generally not dangerous, however some side effects may be serious and can be considered life-threatening.
Common side effects of SGLT2 inhibitors include:
- Genital yeast infections including vaginal, vulvar and penile (banal) infections
- Urinary tract infection including bladder and kidney infections
- Photosensitivity or sun intolerance
- Rash and itching, often from yeast infection on skin
- Fatigue or loss of energy
More severe side effects of SGLT2 inhibitors may warrant emergency medical action.
The Food and Drug Administration (FDA) issued a medical warning in May 2015 regarding the risk of diabetic ketosis (DKA) in patients taking SGLT2 inhibitors including Invokana, Farxiga and Jardiance. Between March 2013 and April 2014, at least 20 cases of DKA had been reported to the FDA.
Diabetic ketoacidosis is caused by high levels of ketones in the bloodstream which are produced by the body when it is unable to use glucose in the cells. The ketones are a byproduct of fat metabolism and are acidic in nature. The disorder can quickly deteriorate and become life-threatening.
Symptoms of diabetic ketoacidosis or ketosis may include:
- Increased thirst and urination
- Excessive hunger
- Abdominal pain or nausea
- Fatigue, Weakness, Dizziness
- Shortness of breath, Sweating, Rapid heart beat
- “Fruity” odor to the breath
If the patient does not receive treatment, the following symptoms may occur:
- Confusion or extreme irritability
- Dizziness or Fainting
- Trouble breathing
If left untreated, diabetic ketoacidosis is life-threatening.
Unfortunately, many Type 2 diabetics will not recognize the symptoms and the original prescribing information and patient instructions did not list diabetic ketoacidosis as a concern.
Other Serious Side Effects
In addition, the medical data company, IMS has identified hundreds of additional serious adverse events that occurred in patients who took the newer SGLT2 inhibitor antidiabetic medications. The newer diabetic medications may also cause:
- Low blood pressure
- Changes in laboratory blood levels of potassium, cholesterol, hemoglobin and others
- Decreased kidney function
- Allergic reactions
Some medical professionals, including several FDA advisory committee members have expressed concern about an increased risk of heart attack and companies have been ordered to complete additional safety studies of the effects on the heart, bones, and liver and to investigate the risk of cancer and pregnancy risk.
Farxiga was the first SGLT2 drug the FDA considered for approval. The application was initially denied based on a concern about liver failure. Invokana was approved in March 2013 after an FDA advisory panel voted 10 to 5 for approval though some advisory panel members expressed concern about the drug’s potentially increased risk for heart attack. Farxiga was finally approved in January of 2014 and Jardiance in August of 2014 even though Diabetic Ketoacidosis reports had already began to be received by the FDA.
In January of 2013, the consumer advocacy group, Public Citizen, filed an objection to Invokana. The group stated that not enough safety information was available about the medication and that prior “new” antidiabetic drugs had proven troublesome. Many of these drugs have resulted in thousands of lawsuits due to serious adverse events caused by the medications.
Public Citizen has also objected to advertising regarding the SGLT2 medications stating that “reduced blood pressure” as claimed by the medication’s marketing material is not a benefit, but a potentially harmful side effect as described in the literature. They have also objected to the non-approved claim that “some” patients may lose weight on these medications as the notification often appears close to the approved indications which the group feels may be confusing and cause some to believe the medication is approved for use as a weight loss agent. Public Citizen has all three medications on its “Do Not Use” list on its website.
In May 2015, the FDA issued a warning letter regarding the risk of diabetic ketoacidosis, citing 20 serious adverse events reports the agency had received. Prescribing information for the medications has listed a “contraindication” (reason against use) for patients with DKA but literature contains no clear warning about the risk.
In addition, serious adverse event reporting is “voluntary” and more cases of SGLT2-related DKA may exist and additional events may yet occur. In 2014, an estimated 2 million Invokana prescriptions were filled and Farxiga was the 8th best-selling new prescription medication.
Farxiga, Invokana and Jardiance Lawsuits
In the recent past, thousands of lawsuits have been filed and settled for newer antidiabetic medications which have caused medical injury.
It is not yet known how many patients may be injured by the SGLT2 inhibitors but IMS health data indicates that thousands of serious adverse events including diabetic ketoacidosis may be expected.
Injury caused by medications, particularly those for diabetes may result in a need for expensive medical treatments, hospitalization and long-term medical care. Those patients may be eligible for compensation for medical costs, lost wages, future medical treatments and pain and suffering. In some cases, the families of victims who die after using certain medications may be eligible for compensation for wrongful death.
Each occurrence of medical injury that is thought to be caused by a drug must be considered individually as the circumstances for each case are different. In some cases, patients have been eligible for thousands or even millions of dollars compensation but there is no guarantee of award.