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Sodium‐glucose co‐transporter inhibitors as adjunctive treatment to insulin in type 1 diabetes: A review of randomized controlled trials
Author(s) -
Boeder Schafer,
Edelman Steven V.
Publication year - 2019
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13749
Subject(s) - dapagliflozin , medicine , insulin , placebo , type 2 diabetes , diabetes mellitus , adjunctive treatment , diabetic ketoacidosis , randomized controlled trial , type 1 diabetes , endocrinology , pharmacology , alternative medicine , pathology
Many patients with type 1 diabetes (T1D) struggle to achieve glycaemic control and experience significant fluctuations in glucose concentrations, despite insulin treatment. Sodium‐glucose co‐transporter (SGLT)‐2 inhibitors and dual SGLT‐1/2 inhibitors increase glucose elimination via the kidneys and reduce hyperglycaemia via insulin‐independent mechanisms. This review examines available efficacy and safety data for these agents under investigation as adjunctive therapy for T1D. Across randomized trials of up to 52 weeks, SGLT‐2 inhibitors or SGLT‐1/2 inhibitors as an adjunct to insulin demonstrated significant reductions in glycated haemoglobin, glucose exposure, and measures of glycaemic variability, as well as increased time in the target glycaemic range, compared with placebo. Non‐glycaemic benefits included reductions in body weight and insulin doses, as well as improvements in some cardiovascular risk factors and treatment satisfaction. SGLT‐2 inhibitors and SGLT‐1/2 inhibitors were associated with similar rates of hypoglycaemia but a higher incidence of genitourinary infections, compared with placebo. Diabetic ketoacidosis occurred more often with SGLT‐2 inhibitors and SGLT‐1/2 inhibitors vs placebo, although the incidence was generally low. Risk mitigation strategies in light of clinical trial data are also discussed. Positive data from randomized controlled trials of the SGLT‐2 inhibitor dapagliflozin have led to the approval of dapagliflozin as an adjunct to insulin in adults with T1D having body mass index ≥27 kg/m 2 in whom insulin does not provide adequate glycaemic control in Europe and to approval as an adjunct to insulin for adults with T1D in Japan.