Sodium-Glucose Cotransporter Inhibitors for the Treatment of Type 1 Diabetes Mellitus
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REVIEW ARTICLE
Sodium‑Glucose Cotransporter Inhibitors for the Treatment of Type 1 Diabetes Mellitus Ning Li1 · Ruimin Chen1 · Kewei Liu1
© Springer Nature Switzerland AG 2020
Abstract Sodium-glucose cotransporter inhibitors are a new class of oral antihyperglycemic drugs that have been approved for the treatment of patients with type 2 diabetes mellitus. Sodium-glucose cotransporter inhibitors reduce glucose reabsorption in the kidneys, which lowers blood glucose. In addition, they offer significant cardiovascular benefits and renal protection. Multiple phase III trials of sodium-glucose cotransporter inhibitors in patients with type 1 diabetes have been completed. The European Medicines Agency approved dapagliflozin as an adjuvant therapy to insulin for patients with type 1 diabetes who have poor blood glucose control with the optimal dose of insulin alone (body mass index ≥ 27 kg/m 2). As adjuvants to insulin for patients with type 1 diabetes, sodium-glucose cotransporter inhibitors improve blood glucose control and reduce total daily insulin dose and body weight. However, there is also concern about diabetic ketoacidosis caused by sodium-glucose cotransporter inhibitors. In this review, the mechanisms of hypoglycemic action, pharmacokinetics, clinical efficacy, and safety of sodium-glucose cotransporter inhibitors for the treatment of type 1 diabetes are discussed.
1 Introduction Type 1 diabetes mellitus is a chronic disease characterized by autoimmune-mediated destruction of B cells, resulting in reduced insulin secretion or an absolute deficiency [1, 2]. The occurrence of the disease may be related to autoimmune disorders or environmental factors [3–5]. The incidence of type 1 diabetes varies from country to country. East Asian and American Indian populations have the lowest incidence (0.1–8 per 100,000), while Finland has the highest incidence (64.2 per 100,000) [6]. Type 1 diabetes is more common in children and adolescents, but it can occur at any age and requires life-long dependence on insulin therapy [7]. Fewer than one in five children and adolescents with type 1 diabetes in the USA meet the glycosylated hemoglobin ( HbA 1c) values ( 20 years (interaction trend p-value 0.004) [20]. Another DAPA-HF study assessing the role of dapagliflozin in patients with heart failure and a reduced ejection fraction showed that the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes [21]. Based on these two studies, the US Food and Drug Administration granted dapagliflozin fast-track status for adult patients with heart failure. Sodium-glucose cotransporter-1 is mainly localized in the small intestine [14]. The SGLT-1/2 dual inhibitor sotagliflozin is different from SGLT-2 inhibitors; it can work with the kidneys and intestines to reduce glucose absorption [22]. In March 2019, dapagliflozin was successively approved in Europe and Japan as an oral adjuvant therap
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