The FDA voted, in March 2013, to approve Invokana, a drug used in the treatment of Type 2 diabetes. The vote was 10 to five in favor of the approval for the drug developed by Janssen Pharmaceuticals and Johnson & Johnson. Invokana was soon followed by additional SGLT-2 inhibitor drugs such as Farxiga, Jardiance, Invokamet, Xigduo XR and Glyxambi.
Two of these drugs (Xigduo XR and Invokamet) add metformin to the SGLT-2 inhibitor drug, and Glyxambi combines SGLT-2 and DPP-4 inhibitors. Farxiga received approval in Europe prior to receiving FDA approval in the United States. Yet after only one year following the FDA’s approval of Invokana, the agency had received more than 450 adverse event reports from patients taking the drug. At least 54 of those adverse event reports were associated with renal failure.
A Short History of SGLT-2s
The SGLT-2 drug class dates back as far as 1835, when French chemists isolated a substance from the bark of apple trees known as phlorizin. By 1886 a German physician demonstrated the ingestion of high dosages of phlorizin resulted in glucose being expelled from the urine. A full century elapsed before researchers began recognizing the potential of phlorizin to treat Type 2 diabetes. The substance worked well to improve glycemic control in diabetic animals, however unpleasant gastrointestinal side effects were present. Eventually phlorizin’s ability to induce glucosuria (the excretion of glucose into the urine) was replicated in a lab, ostensibly doing away with the unpleasant side effects.
How SGLT-2 Inhibitors Work in the Body
SGLT-2 inhibitors evolved to prevent the loss of important sugars in the body by transporting glucose from the kidneys back into the body. About 90% of the glucose in the kidneys is reabsorbed by the SGLT-2 inhibitor. The artificial inhibitors decrease the number of natural SGLT-2 proteins, lowering the threshold for glucose excretion which can cause the body to expel 100-300 calories of excess glucose every day. In fact, advertisements for some of the SGLT-2 inhibitor drugs note that weight loss is a welcome side effect of the drug.
Side Effects Associated With SGLT-2 Inhibitors
The side effects such as urinary tract infections and decreases in bone density were not of particular concern for the FDA when considering the approval of the SGLT-2 inhibitor drugs. The infections are likely due to the fact that bacteria and fungi grow more quickly in glucose-rich urine. Although SGLT-2 inhibitors might appear to be the next wonder drug in the treatment of Type 2 diabetes, the drugs do not appear as impressive when compared to older diabetic drugs such as metformin—and when taking potentially serious side effects into account.
Due to the increasing number of patients who are experiencing serious side effects associated with Invokana and other SGLT-2 inhibitor drugs, the drugs should possibly be considered as a second or third line therapy rather than the first choice. Because SGLT-2 inhibitors appear to worsen already-impaired kidney functions, this may limit the drug’s usefulness. Other serious side effects include the development of potentially fatal ketoacidosis, heart attack and stroke.
Understanding the Legal Issue of Failure to Warn
Because SGLT-2 inhibitors have such a long history and because the FDA received so many adverse event reports regarding these drugs in one year alone, it seems unlikely that Johnson & Johnson and Janssen were totally unaware of the potential risks associated with Invokana. In order to be found guilty of failure to warn, several factors must be present such as:
- The manufacturer was aware of the dangers associated with the drug. A manufacturer may claim ignorance of the dangers, however in the case of Invokana, it seems Johnson & Johnson and Janssen could reasonably be expected to have been aware of some of the potential dangers of the drug.
- The manufacturer has a specific duty to warn consumers of any potential dangers. If J & J and Janssen knew of the inherent risks associated with Invokana and did not warn consumers of those risks, then liability may be present.
- The manufacturer was negligent regarding the duty to warn. It must be shown that the manufacturers were knowledgeable and responsible for the dangers of the drug and that they failed to take proper action in warning about the danger. The warning must be visible and informative to the consumer and should contain a word indicating risk such as “caution,” or “warning.”
- The Plaintiff was injured as a direct result of inadequate warnings or no warnings.
While failing to adequately warn consumers regarding potentially harmful side effects associated with Invokana, Johnson & Johnson recorded $278 million in sales during the first quarter of 2015. The drug is expected by many to reach blockbuster status during 2015, meaning it will pass the $1 million mark.