Effectiveness and Safety of Oral Quadruple Combination Therapy in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis.

Background: Achieving optimal glucose control is essential in the management of type 2 diabetes (T2D). This study aimed to evaluate the effectiveness and safety of oral quadruple combination therapy for the treatment of T2D.

Methods: This meta-analysis reviewed original research on oral quadruple combination therapy for T2D, including both experimental and observational studies with a minimum duration of 12 weeks. The primary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to follow-up. The secondary endpoint was the incidence rate of adverse events. Two investigators independently extracted data and assessed the risk of bias. Outcomes were pooled as the standardized mean difference (using Hedge's g) and the risk ratio for adverse events in random-effects meta-analyses.

Results: The meta-analysis included 17 studies. Oral quadruple combination therapy resulted in an additional mean reduction in HbA1c levels of 1.1% in patients who did not achieve glycemic control with oral triple combination therapy. Compared with switching to injectables, such as insulin or a glucagon-like peptide-1 receptor agonist-containing regimen, this therapy was non-inferior, even demonstrating a slightly superior glucose-lowering effect. Furthermore, it was determined to be safe, with an adverse event rate of 0.25, indicating no significant difference in safety compared with adding a placebo or switching to an injectable-containing regimen.

Conclusion: Oral quadruple combination therapy is a valid option for patients with T2D who are unable to achieve glycemic targets with oral triple combination therapy, offering both effective glycemic control and a favorable safety profile.