Insulin monotherapy compared with the addition of oral glucose‐lowering agents to insulin for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control

Background It is unclear whether people with type 2 diabetes mellitus on insulin monotherapy who do not achieve adequate glycaemic control should continue insulin as monotherapy or can benefit from adding oral glucose‐lowering agents to the insulin therapy. Objectives To assess the effects of insulin monotherapy compared with the addition of oral glucose‐lowering agents to insulin monotherapy for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and reference lists of articles. The date of the last search was November 2015 for all databases. Selection criteria Randomised controlled clinical trials of at least two months' duration comparing insulin monotherapy with combinations of insulin with one or more oral glucose‐lowering agent in people with type 2 diabetes. Data collection and analysis Two review authors independently selected trials, assessed risk of bias, extracted data and evaluated overall quality of the evidence using GRADE. We summarised data statistically if they were available, sufficiently similar and of sufficient quality. We performed statistical analyses according to the statistical guidelines in the Cochrane Handbook for Systematic Reviews of Interventions. Main results We included 37 trials with 40 treatment comparisons involving 3227 participants. The duration of the interventions ranged from 2 to 12 months for parallel trials and two to four months for cross‐over trials. The majority of trials had an unclear risk of bias in several risk of bias domains. Fourteen trials showed a high risk of bias, mainly for performance and detection bias. Insulin monotherapy, including once‐daily long‐acting, once‐daily intermediate‐acting, twice‐daily premixed insulin, and basal‐bolus regimens (multiple injections), was compared to insulin in combination with sulphonylureas (17 comparisons: glibenclamide = 11, glipizide = 2, tolazamide = 2, gliclazide = 1, glimepiride = 1), metformin (11 comparisons), pioglitazone (four comparisons), alpha‐glucosidase inhibitors (four comparisons: acarbose = 3, miglitol = 1), dipeptidyl peptidase‐4 inhibitors (DPP‐4 inhibitors) (three comparisons: vildagliptin = 1, sitagliptin = 1, saxagliptin = 1) and the combination of metformin and glimepiride (one comparison).