Invokamet, used for the treatment of type-2 diabetes, has been implicated in lower limb amputations among patients who have taken the medication. Invokamet is a combination therapy, consisting of canagliflozin (Invokana) and metformin, approved in 2013 and manufactured by Janssen Pharmaceuticals, a division of Johnson & Johnson.

Janssen, along with other drug companies that produce similar medications of the gliflozin class, is currently facing litigation over injuries allegedly caused by these products.

How Does Invokamet Work?

Invokamet and Invokana are part of a class of medications known as sodium-glucose co-transporter 2 (SGLT2) inhibitors. Other SGLT2 inhibitors FDA-approved drugs of this class include:

• dapagliflozin (Farxiga, developed jointly by Bristol-Meyer Squibb and AstraZeneca)
• empagliflozin (Jardiance, a product of Boehringer Ingelheim).
• ertugliflozin (Steglatro, manufactured by Merck and Pfizer)

Medications of this class target a specific protein in the kidneys that play a significant part in maintaining healthy glucose levels. SGLT2 facilitates reabsorption of excess glucose from the blood, releasing it back into the bloodstream. Drugs such as Invokamet, used for controlling blood sugar levels, prevent this process; instead, excess glucose is passed out of the patient’s body through urination (a process known as glucosuria).

How Does Invokamet Increase Amputation Risk?

The exact mechanism of how SGLT2 inhibitors cause an elevated risk of amputation is not fully understood. At least one study has noted that amputations are more likely among patients taking canagliflozin as opposed to those taking other medications of the class.

One possible explanation may be the way canagliflozin affects circulation. Doctors have theorized that canagliflozin thickens the blood, which in turn causes it to pool in the lower extremities.

At a January of 2013 meeting of the FDA Endocrinologic and Metabolic Drugs Advisory Committee (EMDA) during which Janssen sought approval for the drug, one prominent physician noted that SGLT2 inhibitors could cause a rise in the concentration of red blood cells, which can have a thickening effect on the blood.

This theory was reinforced by a study presented at the 2018 meeting of the European Association for the Study of Diabetes in which diabetic patients who took diuretics were found to have twice the risk of amputation as those who did not.

The FDA has also identified other risk factors for lower limb amputation, which include:

• prior history of amputation
• peripheral vascular disease
• nerve damage (neuropathy)
• diabetic foot ulcers

What Else is Invokamet Used For?

There is some evidence to indicate that canagliflozin may reduce the risk of cardiac arrest. For patients suffering from type-2 diabetes, SGLT2 inhibitors may also reduce risks of congestive heart failure and other cardiovascular risks. However, this evidence is not conclusive, nor has Invokamet been approved for this purpose except for diabetic patients.

Are There Other Risks?

Canagliflozin and other SGLT2 inhibitors have been linked to:

• urinary tract infections
• genital infections (including Fournier’s Gangrene)
• elevated LDL cholesterol levels
• hypotension (low blood pressure)
• diabetic ketoacidosis (high acid levels in the blood)