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Effects of sodium‐glucose cotransporter (SGLT) inhibitors in addition to insulin therapy on glucose control and safety outcomes in adults with type 1 diabetes: A meta‐analysis of randomized controlled trials
Author(s) -
Lu Jingli,
Tang Lijuan,
Meng Haiyang,
Zhao Junjie,
Liang Yan
Publication year - 2019
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.3169
Subject(s) - medicine , diabetic ketoacidosis , adverse effect , empagliflozin , placebo , dapagliflozin , randomized controlled trial , diabetes mellitus , relative risk , insulin , type 2 diabetes , cochrane library , gastroenterology , endocrinology , confidence interval , alternative medicine , pathology
Summary Sodium‐glucose cotransporter (SGLT) inhibitors added to insulin therapy have been proposed as treatment strategy for type 1 diabetes (T1D). We thus conducted a meta‐analysis of randomized controlled trials (RCTs) to assess the efficacy and adverse effects of this combination in T1D. We searched the PubMed, EMBASE, and Cochrane Library databases and ClinicalTrials.gov for RCTs. Statistical analyses were performed using STATA 15. Ten eligible placebo‐controlled trials involving 5961 patients were included. Compared with placebo, SGLT inhibitors were associated with a reduction in HbA1c of −0.39% (95% CI, −0.43 to −0.36), an improved mean amplitude of glucose excursion (MAGE) of −14.81 mg/dL (95% CI, −19.08 to −10.54), and a reduction in body weight of −3.47% (95% CI, −3.78 to −3.16), as well as no increased relative risk of hypoglycaemia (1.01; 95% CI, 0.99‐1.02) or severe hypoglycaemia (0.91; 95% CI, 0.77‐1.07). SGLT inhibitors decreased fasting plasma glucose and insulin requirement but increased the risk of genital infection (3.57; 95% CI, 2.97‐4.29) and diabetic ketoacidosis (3.11; 95% CI, 2.11‐4.58). However, the very low dose empagliflozin (2.5 mg) did not increase the risk of diabetic ketoacidosis (risk ratio [RR] 0.67; 95% CI, 0.11‐3.95). SGLT inhibitors had no effect on overall adverse events, urinary tract infection, or bone fracture but slightly increased the risk of serious adverse events (1.35; 95% CI, 1.16‐1.58), severe adverse events (1.84; 95% CI, 1.20‐2.84), adverse events leading to discontinuation (1.50; 95% CI, 1.22‐1.84), drug‐related adverse events (1.78; 95% CI, 1.44‐2.19), and diarrhoea (1.54; 95% CI, 1.15‐2.05). Although adverse events exist, the available data provide evidence that the combination of SGLT inhibitors with basal insulin treatment is beneficial in patients with T1D.