Abstract
Many patients with type 1 diabetes (T1D) do not achieve the glycemic target goal with insulin treatment. In this study, we aimed to evaluate the efficacy and safety of add-on to insulin therapy in patients with T1D. We conducted direct and indirect network meta-analyses using Bayesian models and ranked hypoglycemic agents via mixed treatment comparison, using data from the CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases. Randomized controlled trials (RCTs) involving patients with T1D treated with insulin and add-on metformin or sodium-glucose cotransporter inhibitors or glucagon-like peptide-1 receptor agonists from January 1970 to September 2019 were included in this study. Twenty-three RCTs with 5,151 subjects were divided into the following groups: insulin alone, insulin+metformin, insulin+canagliflozin, insulin+dapagliflozin, insulin+empagliflozin, insulin+sotagliflozin, insulin+liraglutide, and insulin+exenatide. HbA1c level in the insulin+sotagliflozin group was significantly lower than that in the insulin alone group (mean difference: −0.43, 95% credible interval: −0.62 to −0.23). Total daily insulin dose in the insulin+sotagliflozin group was significantly lower than that in the insulin alone group. Compared with that in the insulin alone group, body weight in the groups treated with insulin+add-on canagliflozin, sotagliflozin, and exenatide was significantly decreased by 4.5, 2.8, and 5.1 kg, respectively. Hypoglycemic episodes did not differ among the groups. In patients with T1D, insulin+sotagliflozin decreased the HbA1c level, daily insulin dose, and body weight without hypoglycemia compared with insulin monotherapy. Insulin+canagliflozin or insulin+exenatide was effective in reducing body weight compared with insulin alone. In conclusion, sotagliflozin treatment decreased not only the HbA1c levels and insulin dose but also the body weight without causing hypoglycemia in patients with T1D. Treatment with canagliflozin and exenatide effectively reduced body weight in patients with T1D. However, ketoacidosis associated with the use of SGLT inhibitors should be considered in these patients. Thus, our results suggest that sotagliflozin has a high probability of being ranked first as an adjunctive therapy to insulin in patients with T1D.
Highlights
The incidence of type 1 diabetes (T1D) is continuously increasing
Several drugs have been investigated as an adjunct therapy for T1D, but the US FDA approved only pramlintide, which mimics a β-cell hormone that is co-secreted with insulin in the postprandial period, in 2005 [3]
We evaluated the effect and safety of adding oral hypoglycemic agents or injectable glucagon-like peptide-1 (GLP-1) RAs to insulin therapy in patients with T1D
Summary
The incidence of type 1 diabetes (T1D) is continuously increasing. According to a report from the International Diabetes Federation (IDF), T1D currently affects 29 million adults worldwide [1]. According to the T1D Exchange Registry data, in more than 70% of patients with T1D, glycated hemoglobin (HbA1c) levels lower than 7% was not achieved [2]. Compared with the treatment of type 2 diabetes (T2D) using various novel medications, that of T1D mostly depends on insulin. Several drugs have been investigated as an adjunct therapy for T1D, but the US FDA approved only pramlintide, which mimics a β-cell hormone that is co-secreted with insulin in the postprandial period, in 2005 [3]. The effects of pramlintide on HbA1c level and weight changes are mild and unsatisfactory [4]
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