A Comprehensive Monograph on the Fixed-Dose Combination of Sitagliptin and Metformin

Executive Summary and Introduction

Overview of Sitagliptin/Metformin Combination Therapy

The fixed-dose combination (FDC) of sitagliptin and metformin hydrochloride represents a significant therapeutic modality in the management of type 2 diabetes mellitus (T2DM). This oral antihyperglycemic agent is indicated as an adjunct to diet and exercise to improve glycemic control in adult patients for whom treatment with both sitagliptin and metformin is appropriate.[1] The development and clinical application of this combination therapy reflect a strategic evolution in diabetes management, moving from a traditional, sequential addition of medications to a more proactive approach of using initial or early combination therapy to target the multiple pathophysiological defects inherent in T2DM.[3]

Type 2 diabetes is a chronic and progressive metabolic disorder characterized by insulin resistance, relative insulin deficiency due to pancreatic β-cell dysfunction, and excessive hepatic glucose production.[5] As the disease progresses, monotherapy, typically with metformin, often becomes insufficient to maintain target glycemic control, with over 50% of patients requiring additional therapeutic agents.[5] International and national clinical guidelines now recognize the utility of initiating combination therapy earlier in the treatment course, particularly for patients with higher baseline glycosylated hemoglobin (HbA1c) levels (e.g.,