Our protocol was registered in PROSPERO (CRD42015025727). We followed PRISMA guidelines . This article is based on previously conducted studies and does not involve any new studies of human or animal subjects performed by any of the authors.
Data Sources and Searches
MEDLINE (1946 onward), EMBASE (1947 onward), and the Cochrane Library through to July 2015 were searched for relevant studies. The references of relevant studies were scanned. In addition, we searched clinicaltrials.gov, the World Health Organization Clinical Trials Registry, UpToDate, and Google Scholar. There was no limitation based on language. The search strategy can be found in Electronic Supplementary Material (ESM) Appendix 1.
Relevant studies included those involving patients aged ≥18 years who were taking antihyperglycemic medications for T2DM in any setting. For inclusion in our analysis, the following study designs were eligible, with no minimum follow-up time or sample size: randomized controlled trials, controlled before–after studies, interrupted time series, case–control studies, and prospective and retrospective cohort studies. Included studies compared the spectrum of deprescribing approaches (stopping drug treatment entirely, reducing dose, gradual tapering, or substitution) of at least one medication (insulin, metformin, sulfonylureas, thiazolidinediones, meglitinides, alpha-glucosidase inhibitors, dipeptidyl peptidase IV inhibitors, pramlintide, glucagon-like peptide-1 agonists) to continuing these medications. Included studies had to report on at least one of the following: hypoglycemia, falls, adverse drug reactions, frequency of blood glucose testing, blood glucose levels, HbA1C levels, pill burden, emergency room visits and hospitalizations, quality of life and patient satisfaction, length of stay in hospital, microvascular complications, macrovascular outcomes, polyuria, hyperglycemia, and/or sleep disturbances.
Data Extraction and Quality Assessment
Two independent reviewers screened titles and abstracts and evaluated full-text articles against eligibility criteria. The reviewers independently extracted data from eligible articles using a pilot-tested form. We extracted the following: year, journal, funding, study design, number of participants, proportion of male/female participants, comorbidities, duration of diabetes, concomitant medications, study medications, doses, frequency, duration and stopping/tapering/switching regimen and outcomes on benefits and harms of deprescribing.
Data Synthesis and Analysis
Two independent reviewers conducted risk of bias assessments for eligible studies using Cochrane’s ROBINS-I tool . We conducted a narrative synthesis of results, using methods described in our registered protocol . Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess quality of evidence .