Open AccessMeta-Analysis of 11 Heterogeneous Studies regarding Dipeptidyl Peptidase 4 Inhibitor Add-On Therapy for Type 2 Diabetes Mellitus Patients Treated with Insulin
Author(s) -
Katsuya Shibuki,
Shizuo Shimada,
Takao Aoyama
Publication year - 2020
Publication title -
journal of diabetes research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.034
H-Index - 50
eISSN - 2314-6753
pISSN - 2314-6745
DOI - 10.1155/2020/6321826
Subject(s) - hypoglycemia , medicine , odds ratio , type 2 diabetes mellitus , diabetes mellitus , placebo , type 2 diabetes , body mass index , confidence interval , dipeptidyl peptidase 4 , insulin , incidence (geometry) , meta analysis , dipeptidyl peptidase 4 inhibitor , endocrinology , gastroenterology , pathology , physics , alternative medicine , optics
Background Several clinical trials have addressed the therapeutic strategy of adding dipeptidyl peptidase 4 (DPP-4) inhibitors to the treatment of type 2 diabetes mellitus (DM) inadequately controlled by insulin therapy. However, there is a high degree of heterogeneity in these studies, and the cause of which has not been identified.Methods We conducted a meta-analysis of randomized controlled trials, which compared the efficacy and safety of adding DPP-4 inhibitors or placebo to insulin therapy; the level of hemoglobin A1c (HbA1c) in the patients was >7.0%, and the duration of treatment was ≥8 weeks. We focused on the mean changes in HbA1c from the baseline ( Δ HbA1c) and the incidence of hypoglycemia. We assumed that five baseline parameters (HbA1c, fasting blood glucose, body mass index (BMI), duration of type 2 DM, and duration of treatment) could affect Δ HbA1c. Regarding the incidence of hypoglycemia, we suspected that the heterogeneity was caused by differences in the definition of hypoglycemia among the studies.Results Data obtained from 11 studies ( n = 4654 patients) were included in the analysis. The mean Δ HbA1c between the DPP-4 inhibitor and placebo groups was -0.61% (95% confidence interval (CI): -0.74 to -0.48, I 2 = 73.4%). There was substantial heterogeneity among the 11 studies, but 74.1% of this variability was explained by the difference in BMI. The odds ratio for the incidence of hypoglycemia was 1.02 (95% CI: 0.74 to 1.42, I 2 = 63.8%), with substantial heterogeneity due to differences in the definition of hypoglycemia among the studies. There was no apparent effect of publication bias.Conclusions The addition of DPP-4 inhibitors to insulin therapy for adult patients with type 2 DM can significantly reduce HbA1c levels without increasing the occurrence of hypoglycemia. BMI and hypoglycemia definition could explain the heterogeneity in the clinical trials. This trial is registered with PROSPERO #CRD42016035994.