Prevalence, Glycemic Efficacy, and Safety of Four Non-Insulin Antidiabetic Drug Combinations in Patients with Type 2 Diabetes.

INTRODUCTION: Only a few studies have investigated the prevalence and safety of oral quadruple regimens for treating type 2 diabetes (T2D), and evidence regarding combinations that include glucagon-like peptide-1 receptor (GLP-1R) agonists remains limited.

METHODS: A descriptive, retrospective, cross-sectional study was conducted to collect information on the use of four non-insulin drug combinations in patients with T2D over a 12-month period.

RESULTS: A total of 1,463 patients with T2D were evaluated during the study period, of whom 13.7% met the inclusion criteria and were enrolled. The mean duration of quadruple therapy was 37.0 ± 23.3 months. Sodium-glucose co-transporter-2 (SGLT2) inhibitors were the most common add-on therapy to a prior triple-drug regimen (32.3%), followed by pioglitazone (30.4%), sulfonylureas (21.9%), and GLP-1R agonists (12.9%). The mean reduction in glycated hemoglobin A1c (A1C) during quadruple therapy was 0.98 ± 0.88% compared to baseline values (p < 0.001), with no significant adverse effects or safety concerns reported. Notably, the addition of GLP-1R agonists as the fourth drug resulted in greater weight loss than any other oral antidiabetic medication.

DISCUSSION: Despite the limitations inherent to a retrospective design, this study demonstrates that quadruple regimens can achieve significant reductions in A1C levels while maintaining a favorable safety profile.

CONCLUSION: In this study, 13.7% of patients with T2D received quadruple non-insulin drug combinations. Larger randomized controlled trials are needed to further evaluate their safety, efficacy, limitations, and potential role in T2D management.