SGLT-2 inhibitors and lower limb amputation risk in people with type 2 diabetes

This study wanted to find out if treating type 2 diabetes with SGLT-2 inhibitors increases the risk of disease in blood vessels or the risk of amputation of the feet. The study found that treating type 2 diabetes with certain SGLT-2 inhibitors such as canagliflozin (Invokana) may be associated with an increased risk of disease in the blood vessels, and the risk of amputation of the feet. 

Type 2 diabetes (T2D) can have some complications. Peripheral artery disease (PAD) is a complication which occurs when the blood vessels in the lower limbs are narrowed, and therefore blood flow is restricted. This can sometimes result in the need to amputate the toes or feet.

T2D can have many types of treatments, depending on the severity of diabetes. SGLT-2 inhibitors such as canagliflozin, dapagliflozin (Forxiga), or empagliflozin (Jardiance) work by preventing the body from reabsorbing sugar. This means that excess sugar in the blood is removed in the urine. There have been some studies that show that there may be an increased risk of PAD and lower limb amputation in patients who are taking SGLT-2 inhibitors. This has not been looked at across multiple studies. 

This study combined results from 27 smaller studies. The exact type of SGLT-2 inhibitor was variable between the trials. The types of SGLT-2 inhibitors which were examined in this analysis were dapagliflozin, canagliflozin, empagliflozin, and ertugliflozin (Steglatro). This study had overall 29404 patients with T2D who were treated with an SGLT-2 inhibitor. There were also 21556 patients who did not take an SGLT-2 inhibitor. The results were compared between patients who did and did not take SGLT-2 inhibitors. On average the patients were treated for 84 weeks. 

Of the 27 studies analyzed, 14 of the trials had patients with PAD or lower limb amputation. 301 of these cases were in patients who were treated with SGLT-2 inhibitors. 177 of these cases were in patients who were not treated with SGLT-2 inhibitors.

Patients taking SGLT-2 inhibitors were 26% more likely to have PAD or a lower limb amputation than those not taking the medication. When statistically analyzed, canagliflozin was the medication with the highest risk of PAD or lower limb amputation. 

The study concluded that SGLT-2 inhibitors, particularly canagliflozin, may be associated with an increased risk of peripheral artery disease and lower limb amputation in patients with type 2 diabetes. 

This is a study which analyzed results from many smaller studies with different protocols. The definition of PAD in the trials was different. This might have affected the results.

Talk to your doctor if you have concerns about your medication for T2D.