Non-Insulin Antidiabetes Treatment in Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis

In order to evaluate the efficacy and side effects of the non-insulin antidiabetes medications as an adjunct treatment in type 1 diabetes mellitus (T1DM), we conducted systematic searches in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials published between the date of inception and March 2020 to produce a systematic review and meta-analysis. Overall, 57 studies were included. Compared with placebo, antidiabetes agents in adjunct to insulin treatment resulted in significant reduction in glycosylated hemoglobin (weighted mean difference [WMD], -0.30%; 95% confidence interval [CI], -0.34 to -0.25%; P<0.01) and body weight (WMD, -2.15 kg; 95% CI, -2.77 to -1.53 kg; P<0.01), and required a significantly lower dosage of insulin (WMD, -5.17 unit/day; 95% CI, -6.77 to -3.57 unit/day; P<0.01). Compared with placebo, antidiabetes agents in adjunct to insulin treatment increased the risk of hypoglycemia (relative risk [RR], 1.04; 95% CI, 1.01 to 1.08; P=0.02) and gastrointestinal side effects (RR, 1.99; 95% CI, 1.61 to 2.46; P<0.01) in patients with T1DM. Compared with placebo, the use of non-insulin antidiabetes agents in addition to insulin could lead to glycemic improvement, weight control and lower insulin dosage, while they might be associated with increased risks of hypoglycemia and gastrointestinal side effects in patients with T1DM.