A Network Meta-Analysis of the Dose–Response Effects of Dapagliflozin on Efficacy and Safety in Adults With Type 1 Diabetes

Abstract

BackgroundMost patients with type 1 diabetes (T1DM) do not reach the blood glucose goal with treatment of insulin. In our research, we intended to estimate the therapeutic effect and safety of additional different doses of dapagliflozin on insulin treatment in T1DM.MethodsWe performed direct and indirect network meta-analysis using Bayesian models and graded different dosages of dapagliflozin by mixed therapy contrasts. We retrieved information from the PubMed, Embase, The Cochrane Library, Web of Science, China Biology Medicine (CBM) disc, China National Knowledge Infrastructure (CNKI), Wanfang Data, and WEIPU Data. Our research included randomized controlled trials (RCTs) including T1DM treated with insulin and additional dapagliflozin 5 mg or dapagliflozin 10 mg from January 2012 to June 2021. Thirteen RCTs with 10,701 participants were divided into three groups as below: insulin alone, dapagliflozin 5 mg + insulin, and dapagliflozin 10 mg + insulin.ResultsDapagliflozin dose-dependently exhibited reductions in glycated hemoglobin (HbA1c), total insulin daily dose (TDD), and body weight. Neither dapagliflozin 5 mg nor 10 mg could induce hypoglycemia or severe hypoglycemia. However, both doses of dapagliflozin increased the incidence of diabetic ketoacidosis (DKA) and genital infection.ConclusionsDapagliflozin 10 mg could achieve a better outcome in efficacy and could not increase the risk of hypoglycemia. Although it may induce a higher risk of DKA and genital infection, there was no significant difference between dapagliflozin 10 mg and 5 mg. Our outcomes indicate that dapagliflozin 10mg has a high reliability of being graded prior as a supplementary treatment to insulin in T1DM.

Therapeutic effect and rebound evaluation of dapagliflozin on glycated hemoglobin (HbA1c) in type 1 diabetes mellitus patients

“… Wang et al (2022 ) explored the quantitative relationship between dapagliflozin and loss of weight in T1DM patients and found that to achieve the plateau period in the loss of weight, 5 mg/day dapagliflozin was required for at least 41.6 weeks. Li et al (2022 ) found that dapagliflozin treatment significantly decreased HbA1c, insulin dosage, and body weight without increasing the risk of hypoglycemia in T1DM. However, the actual drug efficacy of dapagliflozin on HbA1c and whether there is a rebound from dapagliflozin efficacy on HbA1c remained unknown and thus cannot effectively guide an appropriate use of clinical medication.…”

“…Dapagliflozin, a sodium–glucose cotransporter-2 inhibitor, has been approved for the treatment of type 2 DM (T2DM) ( Curovic et al, 2022 ; Lazzaroni et al, 2022 ). The mechanism of dapagliflozin is to promote glycemic disposal in an insulin-independent way, thereby decreasing postprandial glycemia and glycemic excursions accompanied by an inferior insulin demand without increasing the risk of hypoglycemia ( Li et al, 2022 ). It is interesting to note that research results suggest that dapagliflozin is a promising adjunct treatment to insulin which improves glycemic control in patients with inadequately controlled T1DM ( Dandona et al, 2017 ; Mathieu et al, 2018 ; Parkinson et al, 2019 ; Araki et al, 2020 ; Araki et al, 2021 ; Biester et al, 2021 ); meanwhile, it significantly decreases the glycated hemoglobin (HbA1c) ( Li et al, 2022 ).…”

“…The mechanism of dapagliflozin is to promote glycemic disposal in an insulin-independent way, thereby decreasing postprandial glycemia and glycemic excursions accompanied by an inferior insulin demand without increasing the risk of hypoglycemia ( Li et al, 2022 ). It is interesting to note that research results suggest that dapagliflozin is a promising adjunct treatment to insulin which improves glycemic control in patients with inadequately controlled T1DM ( Dandona et al, 2017 ; Mathieu et al, 2018 ; Parkinson et al, 2019 ; Araki et al, 2020 ; Araki et al, 2021 ; Biester et al, 2021 ); meanwhile, it significantly decreases the glycated hemoglobin (HbA1c) ( Li et al, 2022 ). HbA1c identifies average plasma glucose concentration, and for people with diabetes this is important as the higher the HbA1c, the greater the risk of developing diabetes-related complications ( Rydberg et al, 2022 ; Wikstrom et al, 2022 ).…”

The emergence of obesity in type 1 diabetes

“…Dapagliflozin, the first-in-class SGLT2 inhibitor, was the subject of several trials, however, no conclusive advice on the optimal dose can be drawn [ 84 ]. A network meta-analysis of 13 RCTs ( n = 10,701) highlighted that treatment with dapagliflozin 5 mg and 10 mg decreased body weight from the baseline at MD: −3.2% (95%CI: −3.5 to −2.9%) and MD: −4.2% (95%CI: −4.6 to −3.9%) [ 84 ]. Maximum HbA1c efficacy of dapagliflozin was estimated to be −6.2% at week 9, irrespective of dapagliflozin doses.…”