Long-Term Effectiveness and Safety of SGLT-2 Inhibitors in an Italian Cohort of Patients with Type 2 Diabetes Mellitus.

Maria Mirabelli,Antonio Brunetti,Domenica Maria Corigliano,Luigi Puccio,Biagio Arcidiacono,Patrizia Caroleo,Francesco Saverio Brunetti,Raffaella Vero,Eusebio Chiefari,Daniela Patrizia Foti

doi:10.1155/2019/3971060

Abstract

Background SGLT-2 (sodium-glucose cotransporter-2) inhibitors are a novel class of oral hypoglycemic agents for the management of type 2 diabetes mellitus (T2DM). Herein, we aimed to assess the long-term effectiveness and safety of SGLT-2 inhibitors in a Southern Italy population of subjects affected by T2DM. Patients and Methods 408 diabetic patients treated with one of the three SGLT-2 inhibitors currently available in Italy (dapagliflozin, empagliflozin, and canagliflozin), either alone or in combination with other antidiabetic drugs, were retrospectively assessed at baseline, during, and after 18 months of continuous therapy. Results Treatment with SGLT-2 inhibitors resulted in a median decrease in HbA1c of 0.9%, with a percentage of decrement of 12 in relation to the baseline value, followed by a significant reduction (P < 0.001) in fasting plasma glucose. Variations in HbA1c occurred independently of the baseline clinical or biochemical characteristics. In addition, treatment with SGLT-2 inhibitors reduced body weight (P < 0.008) and decreased diastolic blood pressure (P = 0.004). With regard to safety outcomes, 66 patients out of 91 stopped SGLT-2 inhibitors during follow-up because of chronic or recurring genital infections, while the rest experienced other adverse events, such as urinary tract infections, polyuria, nausea, hypotension, dizziness, acute coronary event, worsening of glycemic control status, and rapid deterioration of renal function. Conclusion In our patients' population, the glycometabolic effects of SGLT-2 inhibitors were durable and comparable to those observed in multicenter randomized controlled trials. This notwithstanding safety concerns must be raised regarding the frequent occurrence of genitourinary infections and the risk of a rapid decline of renal function in patients with evidence of volume depletion and/or receiving other medications which can adversely affect kidney function.

Highlights

Over the last four decades, the global prevalence of type 2 diabetes mellitus (T2DM) has quadrupled, in parallel to that of obesity [1], because of a more westernized lifestyle, responsible for most of the excess weight in the modern adult’s life [2]
SGLT-2 inhibitors are the last class of antidiabetic drugs approved by FDA and EMA regulatory agencies, which could be used in any stage of T2DM, irrespective of comedications
Sex, body mass index (BMI), blood pressure (BP), lipid profile, fasting plasma glucose (FPG), HbA1c, aspartate aminotransferase/alanine aminotransferase (AST/ALT), serum creatinine, duration of diabetes, micro- and macrovascular complications of T2DM, and any concomitant pharmacological therapy were recorded at baseline for all patients

Summary

Introduction

Over the last four decades, the global prevalence of type 2 diabetes mellitus (T2DM) has quadrupled, in parallel to that of obesity [1], because of a more westernized lifestyle, responsible for most of the excess weight in the modern adult’s life [2]. Clinical trials and preliminary postmarketing research have highlighted the risk of genitourinary infections, urosepsis, diabetic ketoacidosis, volume depletion, and amputation, especially in the most vulnerable categories of patients with diabetes [18,19,20,21,22] This notwithstanding, so far, only a few observational studies have been conducted on the effectiveness and safety of SGLT-2 inhibitors at a median follow-up of more than one year [23, 24]. In our patients’ population, the glycometabolic effects of SGLT-2 inhibitors were durable and comparable to those observed in multicenter randomized controlled trials This notwithstanding safety concerns must be raised regarding the frequent occurrence of genitourinary infections and the risk of a rapid decline of renal function in patients with evidence of volume depletion and/or receiving other medications which can adversely affect kidney function

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