T1DM is characterized by deficient insulin production, requiring multiple daily insulin doses. However, glycemic control is often suboptimal, and insulin-associated weight gain and hypoglycemia are concerns. Therefore, adjunctive therapy may be beneficial. A SLR with searches conducted to 16 Oct 2018 identified phase III/IV RCTs of MET or SGLT1/2 inhibitors as add-on to insulin in T1DM. MEDLINE, Embase and the Cochrane Library were searched, as well as congresses, reference lists and grey literature. Bayesian NMAs were performed at Week 24/26 (Week 24) and Week 52 (Week 52) for change from baseline in HbA1c and weight, and the proportion of participants experiencing hypoglycemic events and hypoglycemic severe adverse events. Nine placebo (PBO) controlled RCTs of dapagliflozin (DAPA), MET, sotagliflozin (SOTA) or empagliflozin (EMPA) reporting results were included. There was some evidence of heterogeneity in study design and outcomes. Results of the NMAs for MET vs. comparator (Table) found that the SGLT2 and SGLT1/2 inhibitors generally performed better than MET for HbA1c and weight, but there were few significant differences for hypoglycemia at Week 52. Results suggest that adjunctive use of SGLT2 and SGLT1/2 inhibitors including DAPA can improve glycemic control compared to MET while enabling weight loss in T1DM, and demonstrate consistent efficacy for the class.
B.E. Langford: Employee; Self; Costello Medical. Research Support; Self; AstraZeneca. M. Evans: Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Mundipharma, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sunovion Pharmaceuticals Inc. T. Haskins-Coulter: Employee; Self; Costello Medical. M. O'Connor: Employee; Self; Costello Medical. H.E. Cant: Employee; Self; Costello Medical. L.A. Eddowes: Employee; Self; Costello Medical. C. Edmonds: Employee; Self; AstraZeneca. A. Tank: Employee; Self; AstraZeneca.
AstraZeneca; Cambridge University