Injectable Antihyperglycemics: A Systematic Review and Critical Analysis of the Literature on Adherence, Persistence, and Health Outcomes

INTRODUCTION: Improving real-world medication adherence to injectable antihyperglycemics in type 2 diabetes mellitus (T2DM) is a clinical challenge. Quantification of the level of adherence required to achieve a minimal clinically important difference (MCID) in glycemic control would assist in meeting this goal. The study objective was to review the literature regarding the relationships of medication adherence and persistence with health outcomes in adult T2DM patients using injectable antihyperglycemics. METHODS: Systematic searches were conducted using electronic databases to identify publications over the last decade. Publications were screened against established eligibility criteria. Study data were extracted, evaluated, and used to identify strengths, limitations, and gaps in current evidence. RESULTS: Eligibility criteria were met by 38 studies, and this report analyzed 34 studies related to glycemic control (n = 25), healthcare resource use (n = 9), and healthcare costs (n = 14). Eight of these studies examined adherence to glucagon-like peptide-1 receptor agonists (GLP-1 RA), including 1 study regarding adherence to GLP-1 RA or to insulin, and 1 study investigating a GLP-1 RA/insulin combination; the remaining studies involved insulin. Studies used a broad range of measures to classify adherence and persistence, and most measures were unable to reliably evaluate the complexities of patient behavior over time. Better adherence to injectable antihyperglycemic medications was generally found to be associated with improved glycemic control, although no studies attempted to identify a MCID. Although higher diabetes-related pharmacy and total healthcare costs were reported for adherent or persistent patients, these patients tended to have lower diabetes-related and all-cause medical costs. CONCLUSION: Results of this review confirmed the effectiveness of injectable antihyperglycemic medications for glycemic control, suggesting that there are clinical and financial consequences to nonadherence. Although attempts were made to quantify the effects of nonadherence, the interpretation of study results was limited by the lack of a MCID and inadequate study design. FUNDING: Novo Nordisk, Inc., Plainsboro Township, NJ, USA. PLAIN LANGUAGE SUMMARY: Plain language summary available for this article. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13300-019-0617-3) contains supplementary material, which is available to authorized users.