A Systematic Review on the Combination of Glipizide and Metformin for Type Two Diabetes

Introduction: Type 2 diabetes mellitus (T2DM) is a chronic and complex metabolic disorder that requires a combination of lifestyle modifications and pharmacological therapies to delay disease-related complications and maintain overall quality of life. This review seeks to systematically evaluate and consolidate the available evidence on clinical effectiveness and safety profile of the glipizide–metformin combination in adults with T2DM. Methods: This review included randomized controlled trials (RCTs), observational, and real-world studies assessing the efficacy and safety of glipizide–metformin combination therapy in adults (≥18 years) with T2DM. Included studies assessed glycemic control, hypoglycemia, weight change, and safety versus placebo, monotherapy, or other oral agents, and were published in English. A literature search was performed in PubMed using appropriate keywords and Medical Subject Headings terms. Results: A total of 12 studies were included in this systematic review. Patients included in these studies were over 50 years old, with ages ranging from 53.5 to 62.8 years. Across eight RCTs the glipizide–metformin combination demonstrated a reduction in glycated hemoglobin (HbA1c) of approximately 0.5–0.8%, accompanied by minimal weight gain. The proportion of patients achieving HbA1c <7% across studies ranged from 8.90% to 70.0%. However, consistent improvements in fasting plasma glucose (FPG) and postprandial glucose (PPG) levels were observed. Episodes of hypoglycemia occurred at a higher frequency with glipizide– metformin, ranging from 12.6% to 100%. Conclusion: This review found that the glipizide–metformin combination effectively improves HbA1c, FPG, and PPG in T2DM patients and is a cost-effective option, especially in resource-limited settings or for noncompliant patients.