Short- and medium-term efficacy of sodium glucose cotransporter 2 (SGLT-2) inhibitors for the treatment of type 1 diabetes: systematic review and meta-analysis.

INTRODUCTION: Sodium glucose cotransporter 2 (SGLT2) inhibitors are insulin-independent and glucose-dependent anti-hyperglycaemic drugs that have shown potential as an adjuvant therapy to insulin for the treatment of type 1 diabetes mellitus (T1DM). The purpose of this meta-analysis is to systematically collect available data from randomised trials to determine SGLT-2 inhibitor efficacy in terms of glycaemic control, body mass index, and renal protection when compared with placebo. MATERIAL AND METHODS: Cochrane Library, MEDLINE, and EMBASE databases were searched for randomised controlled trials and metaanalyses (without language restrictions) conducted from January 2010 to September 2019. RESULTS: Seventeen randomised controlled trials with 7325 participants were included. Sodium glucose cotransporter 2 therapy significantly reduced the level of glycated haemoglobin (HbA1c) (by 0.37%), body weight (by 2.88 kg), and estimated glomerular filtration (eGFR) (by 0.67 mL/min/1.73 m²) when compared with placebo (all outcomes, p < 0.00001). Subgroup analysis by HbA1c levels showed significant differences between six and 12 months of treatment (p < 0.1). The magnitude of the HbA1c lowering effect waned with longer duration of treatment after six months (up to 12 months). Subgroup analysis by body weight showed significant differences between 1 and 3-4 months of treatment (p < 0.1). Weight loss plateaued after 3-4 months of treatment; subsequently, the weight remained relatively stable until 12 months. Subgroup analysis by eGFR showed significant differences between six and 12 months of treatment (p < 0.1). The magnitude of the eGFR lowering effect increased with longer duration of treatment after six months (up to 12 months). CONCLUSIONS: Sodium glucose cotransporter 2 inhibitors show significant therapeutic effects when compared with placebo. Although changes in HbA1c, body weight, and eGFR vary during treatment, the therapeutic effects of SGLT-2 inhibitors measured by these three outcomes can last up to 12 months. More long-term, randomised trials and extended studies are needed to determine the long-term effects of SGLT2 inhibitors as adjuvant therapy for T1DM patients.