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

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 (HbA 1c) (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 HbA 1c levels showed significant differences between six and 12 months of treatment (p < 0.1). The magnitude of the HbA 1c 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 HbA 1c , 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.

The Effect of Sodium–Glucose Cotransporter Inhibitors on Renal Function as Adjunctive to Insulin in Adults with Type 1 Diabetes: An Updated Multilevel Meta-analysis of Randomized Controlled Trials

“…On the basis of the subgroup analysis, both 6-month and 12-month treatment with SGLT inhibitors led to a significant decrease in eGFR. Furthermore, this adverse effect increased with the longer duration of SGLT inhibitor treatment, as a significant difference was observed between the 6-month and 12-month treatment subgroups [ 23 ].…”

Association of British Clinical Diabetologists (ABCD) and Diabetes UK joint position statement and recommendations on the use of sodium-glucose co-transporter inhibitors with insulin for treatment of type 1 diabetes (updated October 2020)

“…[30][31][32][33][34][35][36][37] In a recent meta-analysis including over 7000 participants and 17 randomised controlled trials (RCTs), SGLT inhibitor therapy significantly reduced HbA1c (4 mmol/mol (0.37%)) and body weight (2.88 kg). 38 In another meta-analysis of seven RCTs, lower HbA1c (−3 mmol/mol (−0.28%)), lower insulin dose (MD −0.89) and greater weight loss (−3.03) without any significant difference in hypoglycaemia 39 was seen in the sotagliflozin group.…”

Association of British Clinical Diabetologists (ABCD) and Diabetes UK joint position statement and recommendations on the use of sodium–glucose cotransporter inhibitors with insulin for treatment of type 1 diabetes (Updated October 2020)

“…[30][31][32][33][34][35][36][37] In a recent meta-analysis including over 7000 participants and 17 randomised control trials, SGLT inhibitor therapy significantly reduced HbA 1c (4 mmol/mol [0.37%]) and body weight (2.88 kg). 38 In another meta-analysis of 7 RCTs, lower HbA1c [−3 mmol/mol (−0.28%)], lower insulin dose (MD: −0.89) and greater weight loss (−3.03), without any significant difference in hypoglycaemia 39 was seen in the sotagliflozin group.…”

“…In a recent meta‐analysis including over 7000 participants and 17 randomised control trials, SGLT inhibitor therapy significantly reduced HbA 1c (4 mmol/mol [0.37%]) and body weight (2.88 kg) 38 …”