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08-19-2020 | SGLT2 inhibitors | News

Data reject SLGT2 inhibitor link to increased amputation risk

Author: Laura Cowen


medwireNews: The risk for lower limb amputation is not significantly increased among people using sodium-glucose cotransporter (SGLT)2 inhibitors to treat type 2 diabetes, according to findings from two studies.

Lisa Lix (University of Manitoba, Winnipeg, Canada) and co-authors of the first, observational study explain that up to now reports of amputations associated with SGLT2 inhibitor use “have been inconsistent.”

To address this, they conducted a multicenter cohort study that included 207,817 new SGLT2 inhibitor users matched by time-conditional propensity scores to 207,817 new dipeptidyl peptidase (DPP)-4 inhibitor users from Canada and the UK.

During a mean 11 months of follow-up, the researchers found that there was no significant difference in the below knee amputation rate between SGLT2 inhibitor users and DPP-4 inhibitor users, at 1.3 versus 1.5 cases per 1000 person–years.

Similar results were obtained in stratified analyses by age, sex, prior insulin use, and individual SGLT2 inhibitor molecule (canagliflozin, dapagliflozin, or empagliflozin).

Writing in Diabetes Care, Lix and co-authors conclude: “While these findings provide some reassurance, studies with a longer duration of follow-up are needed to assess potential long-term effects.”

The authors of the second study, Chen-Yu Huang and Jen-Kuang Lee, both from the National Taiwan University College of Medicine and Hospital in Taipei, drew similar conclusions, reporting that “across different subgroups, the use of SGLT-2 inhibitors was not related to higher amputation risk.”

Their findings arose from a quantitative meta‐analysis of six randomized, placebo‐controlled, cardiovascular outcome trials (EMPA‐REG OUTCOME, CANVAS, CREDENCE, DECLARE–TIMI 58, DAPA‐HF, and VERTIS CV) evaluating SGLT2 inhibitors in patients with type 2 diabetes.

The studies included a total of 51,713 participants, of whom 858 needed lower limb amputation.

Huang and Lee found that a numerically higher proportion of patients treated with an SGLT2 inhibitor underwent amputation relative to those treated with placebo, at 2.0% versus 1.3%, but random effects modelling showed that SGLT2 inhibitors were not associated with a significantly increased amputation risk.

Similar results were observed in analyses of various high‐risk subgroups, including patients with peripheral artery disease, a finding that is in line with another recently published study reported by medwireNews.

The researchers also note in Diabetes, Obesity & Metabolism that the main causes of amputation events were critical limb ischemia and infection rather than acute limb ischemia.

And like Lix et al, Huang and Lee suggest: “A multi‐center study focused on major adverse limb events with a longer follow‐up is needed to confirm these results and provide guidelines for clinical practice.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2020 Springer Healthcare Ltd, part of the Springer Nature Group

Diabetes Care 2020; doi:10.2337/dc20-0267
Diabetes Obes Metab; doi:10.1111/dom.14159


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