In 2013, the FDA approved Invokana (canagliflozin), an SGLT2 Inhibitor (sodium glucose co-transporter 2) for Type II diabetics. This drug, intended to help T2 diabetics manage their blood sugar levels, worked in a completely unique way from other glucose management meds. SGLT2 inhibitors filter blood through the kidneys, removing glucose, which is usually later re-distributed through the blood. Instead of the glucose being re-absorbed, Invokana blocks reabsorption, instead releasing excess glucose through urine. Though initially hailed as an innovation in the treatment of T2 diabetes, like many new drugs rushed to market and then prescribed off-brand, it didn’t take long for problems to arise. On May 16, 2017—scarcely 4 years after its market debut—the FDA issued an updated Safety Communication to consumers. Stating that based on new data provided by the results of two large clinical trials, the agency now concluded that the SGLT2 inhibitor canagliflozin—trade named Invokana, Invokamet, or Invokamet XR—placed users at a higher risk of amputations of the foot or leg. Based on the new data, the FDA would now require these products to include a “black box warning”, the most prominent warning the FDA can require of a drug.
The data referenced by the FDA in their Safety Communication are the results of two clinical studies: the CANVAS (Canagliflozin Cardiovascular Assessment Study) and CANVAS-R (A Study of the Effects of Canagliflozin on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus). This research demonstrated that patients who used a a canagliflozin-based drug—such as Invokana, Invokamet, or Invokamet XR—were almost twice as likely to have one or more amputations. “More?” you may find yourself asking—this study provided evidence that use of Invokana or similar canagliflozin-based drug placed users at higher risk for not just “an amputation”, but for multiple amputations. The most common amputations connected to Invokana use are amputations of the toe and middle of the foot. However, because diabetic circulation causes slower healing (small foot wounds become infected, prompting the need to amputate), this means that healing from the amputation itself is also slower and riskier. In some cases, a toe amputation that doesn’t heal correctly can evolve into a whole foot amputation, a partial amputation, even the loss of a whole limb. These studies also showed that users of this drug were at higher risk of above or below the knee amputations, multiple amputations, and in several instances, the loss of both limbs.
