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.