INTRODUCTION: Treatment options for type 2 diabetes are becoming increasingly 
complex with people often prescribed multiple medications, and may include both 
oral and injectable therapies. There is ongoing debate about which drug classes 
provide the optimum second-line and third-line treatment options. In the real 
world, patient adherence and persistence determines medication effectiveness. A 
better understanding of adherence may help inform the choice of second-line and 
third-line drug classes.
METHODS AND ANALYSIS: This systematic review will compare adherence and 
persistence rates across the different classes of medication available to people 
with type 2 diabetes. It will include all identified studies comparing 
medication adherence or persistence between two or more glucose-lowering 
medications in people with type 2 diabetes. Research databases (MEDLINE, EMBASE, 
The Cochrane Library, The Register of Controlled Trials, PsychINFO and CINAHL) 
will be searched for relevant articles, using a comprehensive search strategy. 
All identified medication trials and observational studies will be included 
which compare adherence or persistence across classes of diabetes medication. 
The characteristics and outcomes of all the included studies will be reported 
along with a study quality grade, assessed using the Cochrane Risk Assessment 
Tool. The quality of adjustment for confounders of adherence or persistence will 
be reported for each study. Where multiple (n ≥ 3) studies provide compare 
adherence or persistence across the same 2 medication classes, a meta-analysis 
will be performed.
ETHICS AND DISSEMINATION: No ethics approval is required. This review and 
meta-analysis (where possible) will provide important information on the 
relative patient adherence and persistence, with the different classes of 
diabetes therapies. Once complete, the results will be made available by 
peer-reviewed publication.
TRIAL REGISTRATION NUMBER: CRD42015027865.