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THE ASSOCIATION OF SODIUM-GLUCOSE CO-TRANSPORTERS INHIBITORS AND LOWER LIMB AMPUTATION- A REVIEW OF LITERATURE

Hyder Osman Mirghani, Thomas Antony Thaniyath

In 2015, the global prevalence of diabetes mellitus (DM) has risen to 8.8% [1] and this high incidence of DM is associated with the increasing numbers of individuals with diabetic foot disease. Up to 75% of these patients is going for lower extremity amputations (LEAs) as part of treatment[2]. LEAs reduce the quality of life and increase mortality as well as medical costs[3,4]. Even though an overall reduction in amputations were observed, the incidence of LEAs in diabetic patient is high and it is estimated, one amputation every seven min in subjects ≥ years could be attributed to diabetes mellitus [5].In a review on the incidence of LEA in diabetic patients Narres et al[6] observed a significant decrease in incidence of LEA and this reduction in LEAs is attributed to the improvement in diabetic foot care. Three studies were on empagliflozin, two used dapagliflozin, four on canagliflozin, and eight were on all the three drugs. Three retrospective studies, the CANVAS and CANVAS-R trials, pooled data from fifteen trials, one review, one meta-analysis, a population-based cohort, Data from 4 large US administrative claims databases, A propensity-matched cohort, and 8 293 886 reports analysis. The authors names, year of publication, country, the study design, the numbers of patients included, the duration of follow-up, the final results, and limitations were recorded. SGLT2 inhibitors, a relatively new class of diabetic medication have been shown it effectiveness in glycemic control among type 2 diabetes patients and also showed its potential to improve body mass index, blood pressure, and diabetes-related end-organ complications. Apart from these therapeutic effect, there are some clinical reports that these agents are associated with increased risk for LEA in diabetic patients. Based on findings of this narrative review, as a class of drugs, the SGLT2 inhibitors are not associated with increased risk for lower extremity amputation in type 2 diabetes mellitus patients, when compared oral hypoglycemic agents such as sulphonylureas and placebo. However, some of systematic reviews showed the possibility for the association of canagliflozin with a higher risk of amputation in this patient cohort. Based on these observations, we suggest further systematic evaluation of canagliflozin for its association with increased risk of LEAs in type 2 diabetes mellitus patients.

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