Diabetes drugs like Invokana and Invokamet may increase a patient’s risk of lower limb amputations due to diabetes.

Reportedly, two new large clinical trials have shown that a certain type of diabetes drug can actually make diabetes patients more susceptible to lower-limb amputations than they would be if they had taken no drugs at all.

The news made headlines, worrying patients who took the drug without realizing that it could increase their risk of amputations due to diabetes. P&T Community, among other sources, reported on the canagliflozin research, warning the pharmaceutical community of the serious side effects. 

This link may be concerning to diabetes patients because diabetics are already more susceptible to amputations than the general population, and diabetes medications are supposed to help lower patients’ risk for diabetes symptoms like amputation.

According to the FDA, the diabetes drug canagliflozin, also marketed as Invokana and used in Invokamet and Invokamet XR, can increase a patient’s risk of requiring an amputation of a lower limb. These amputations most often affect the toes and feet, but can also affect the legs. 

Canagliflozin part of a class of diabetes drugs called sodium glucose-cotransporter (SGLT) receptor inhibitors, that are supposed to help manage diabetes by enabling patients to expel excess sugar through their urine. This then helps keep blood sugar low.

The FDA reminds medical professionals that some diabetes patients are at a higher risk than others for amputations due to diabetes in general, and the patients may subsequently have a higher risk of canagliflozin-related amputations. These patients include those with a history of neuropathy, foot ulcers, peripheral vascular disease, and patients who have suffered previous amputations.

People with diabetes are more likely than others to require amputations because diabetes can damage the nervous system, so a person may not notice if they have injured their limb, which may cause the condition to worsen. Additionally, diabetes patients often have difficulty healing from wounds, increasing the possibility that an injury can become severe. This can lead to infection which can then necessitate amputation.

The studies on which the FDA based its warning around canagliflozin drugs like Invokana, Invokamet, and Invokamet XR showed that patients who took canagliflozin were twice as likely to require an amputation as patients who took a placebo. In other words, patients who took canagliflozin were twice as likely to need an amputation as those who did not receive any diabetes treatment at all — treatment that is supposed to lower a patient’s risk for symptoms like amputations due to diabetes.

According to the two large clinical trials, 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), amputations of the toe and middle of the foot were most common. Reportedly, amputations of the leg (below and above the knee) were also required in some cases. Some patients who took canagliflozin required more than one amputation, unfortunately — in some cases, patients had to have both lower limbs amputated.