Initial Pharmacological Strategies in People with Early Type 2 Diabetes Mellitus: A Systematic Review and Network Meta-Analysis

Background: Type 2 diabetes mellitus (T2DM) requires stringent glycemic control from an early stage to prevent complications. The most effective treatment regimen for early T2DM remains unclear. The study aimed to compare the efficacy and safety of monotherapies and combination therapies for early T2DM. Methods: A systematic review and network meta-analysis were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized controlled trials focused on glycemic control, body weight, and adverse events were included. The primary outcomes were changes in glycosylated hemoglobin (HbA1c) and odds of achieving the target HbA1c after 6 months. Results: All combination therapies were more effective than monotherapy. Metformin+glucagon-like peptide-1 receptor agonists (GLP-1RA) (weighted mean difference [WMD] –1.50%; 95% confidence interval [CI] –2.04 to –0.96) and metformin+dipeptidyl peptidase-4 inhibitors (WMD –1.46%; 95% CI, –1.96 to –0.95) were the most effective for change in HbA1c. GLP-1RA and sodium-glucose cotransporter-2 inhibitors led to weight reduction. Apart from the increased risk of hypoglycemia with sulfonylureas, no significant differences in adverse events were observed across regimens. Conclusion: Early combination therapy effectively improved glycemic control in patients with early T2DM without significantly increasing adverse risks. Future studies should explore new combinations, including potent GLP-1RA.