No risk of greater amputation with canagliflozin in patients with T2DM

ORLANDO – Treatment with canagliflozin in patients with type 2 diabetes has not shown increased risk of amputation, according to the OBSERVE-4D study.

New users treated with canagliflozin (Invokana) did not have a significant risk of below-knee amputation (BKA) compared to treatment with other antihyperglycemic agents that were not SGLT inhibitors. -2 (HR 0.75, 95% CI 0.40 -1.41, P= 0.25), reported John Buse, MD, PhD, of the University of North Carolina School of Medicine at Chapel Hill, and his colleagues.

The risk of BKA was generally similar in this category of treatment, and the risk of AK was not significantly different between the use of canagliflozin and other SGLT-2 inhibitors (HR 1, 14, 95% CI 0.67-1.93, P= 0.48), they said at a brief last-minute presentation at the annual meeting of the American Diabetes Association (ADA),

These findings also supported in another analysis in an intention-to-treat population that compared the use of canagliflozin to other SGLT-2 inhibitors (HR 1.13, 95% CI 0.99-). 1.29 P= 0.06), as well as treatment with other antihyperglycemic agents (HR 1.01, 95% CI 0.93-1.10, P= 0.71).

As expected, the cardiac risk was reduced with the use of canagliflozin in the analysis, similar to what was seen in the CANVAS program presented at the 2017 ADA meeting. More specifically, the Buse group found a reduced risk of heart failure with a new use of canagliflozin compared with other antihyperglycemic agents (HR 0.39, 95% CI 0.26-0.60, P= 0.01). The risk of hospitalized heart failure does not differ between the new use of canagliflozin and treatment with other SGLT-2 inhibitors (HR 0.90, 95% CI 0.71-1.13 , P= 0.22).

"Amputations in the CANVAS trial occurred largely in patients who had had amputations – so they had lost a toe – and in the trial, they lost their foot or they lost their leg," explained Buse . MedPage today. "For patients who have not had amputation, who do not have neuropathy, who are not smokers and who do not have advanced peripheral vascular disease, I would be very reassured that there is virtually no risk of amputation, "he added. If he had a patient with heart failure or clinical cardiovascular disease, he would "definitely use an SGLT-2 inhibitor."

"In a patient who has had amputation and heart failure, I could still use an SGLT-2 inhibitor: it's about balancing perceived risks and perceived benefits," he says. he recommended.

In a subgroup analysis of patients with established clinical cardiovascular disease, which included patients who had previously suffered a heart attack, stroke, and other cardiac events, similar effects were observed on the risk of cardiovascular disease. Heart failure and hospital failure.

The real-world analysis used pharmacoepidemiology to appeal to 142,000 canagliflozin users appearing in four different databases on US administration requests. They were compared to 110,000 patients treated with other SGLT-2 inhibitors, including dapagliflozin and empagliflozin, as well as 460,000 patients treated with other antihyperglycemic agents: DPP-4 inhibitors, GLP-1 receptor agonists, thiazolidinediones, sulfonylureas, insulins, acarbose, bromocriptine, miglitol, nateglinide and repaglinide. Among this group of patients, the median exposure to canagliflozin was <6 months.

"The average exposure to a drug in the United States is 6 months, and we can say with a fair degree of certainty that there is no amputation problem in the 39, using an SGLT-2 inhibitor for at least 6 months … being used in the United States, it seems to be fairly safe, "said Buse. He noted that there is less evidence confirming safety with long-term use.

"I think this is to some extent reassuring," said Robert Eckel, MD, of the Anschutz Medical Campus at the University of Colorado. Eckel, who was not involved in the study, warned that a randomized clinical trial is needed to confirm these observed results.

Buse said the results of the OBSERVE-4D study were accepted for publication.

2018-06-24T16: 30: 00-0400