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.

Abstract

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. Cochrane Library, MEDLINE, and EMBASE databases were searched for randomised controlled trials and metaanalyses (without language restrictions) conducted from January 2010 to September 2019. 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). 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.