Clinical Review: Safety and Efficacy Comparison between Sulfonylureas and Dipeptidyl Peptidase-4 Inhibitors as Second-Line Therapies in Type 2 Diabetes Mellitus

Abstract

Background: According to the World Health Organization (WHO), diabetes mellitus is considered the 7th leading cause of death as of 2016, while almost half of all deaths related to high blood glucose occur before the age of 70. According to the 2019 American Diabetes Association’s (ADA) guidelines, metformin is the firstline treatment for patients with Type 2 diabetes. Additional therapy is dependent on multiple patient-specific factors, including cardiovascular risks, risk of hypoglycemia, metabolic changes, and cost. The objective of this systematic review is to analyze variables of interest in Type 2 diabetes including fasting blood glucose (FBG), post-prandial blood glucose (PPBG), hemoglobin A1c (HbA1c), microvascular complications, and cardiovascular outcomes in order to determine the shift towards the newer class of medications for type 2 diabetes. Methods: A systematic review was conducted using ScienceDirect as the primary source of obtaining articles. This review used PRISMA for reporting and GRACE for quality assessment of ten articles. The inclusion criteria for the review consisted of patients who were on metformin therapy for a sufficient amount of time, as defined by the trial’s protocol, and who were then initiated on either a sulfonylurea (glipizide or glimepiride) or a DPP-4 inhibitor (saxagliptin or linagliptin). The articles included in this review range from 2005-2019 that are written in English only. Exclusion criteria for this systematic review were articles in which patients were not initially started on metformin therapy, were diagnosed with Type 1 diabetes mellitus, and articles that were written in languages other than English. Results: After filtering 50 studies, 10 were selected for meeting the criteria of variables of interest. Findings suggested a significant reduction in fasting plasma glucose with 154 mg/dL + 4 mg/dL as baseline, decreasing to 132 mg/dL + 4 mg/dL with the use of glipizide & metformin combination. A similar pattern was presented with the use of saxagliptin and metformin in combination, but changes were less significant than glipizide. However, hypoglycemic events in patients who were taking glipizide with metformin versus saxagliptin with metformin; 13.4% of patients achieved HbA1c <7% without hypoglycemic events compared to 22.2% of the patients who achieved an HbA1c of <7% without hypoglycemic events. Conclusion: Despite the higher efficacious characteristics of sulfonylureas in lowering HbA1c, due to its reported hypoglycemic effects, DPP-4 inhibitors may be considered as a clinically stable choice for second-line therapy after completing maximally tolerated doses of metformin. Sulfonylureas are considered better than DPP-4 inhibitors for treatment in patients with cardiovascular disease history and hypoglycemia.