ObjectiveThe aim of this study was to compare the clinical outcomes associated with different combinations of oral diabetic drugs among patients with type 2 diabetes mellitus.MethodA prospective multicenter longitudinal, noninterventional observation study design was applied. At baseline (0 month), clinical parameters including glucose profile, renal function, lipid profile and risk assessment for cardiovascular risks were calculated. Mean Weighted difference (MWD) with heterogeneity and effect z was calculated to determine the risk reduction at the end of the study.ResultsA total of 1,657 were enrolled to different cohorts with response rate of 75.5%. The distribution of patients was based on prescribed drug. A total of 513 (30.9%) in G1 (metformin alone), 217 (13.09%) in G2 (metformin with Glimepiride), 231 (12.85%) in G3 (Metformin with Gliclazide), 384 (23.17%) in G4 (metformin with Sitagliptin) and 312 (18.89%) in G5 (Metformin with Saxagliptin). There was no significant different in all clinical and social variables at baseline. The Intergroup analysis showed significant differences with all the primary outcome variables except BMI (p = 0.217) and eGFR (p = 0.782) among patients using sulphonylurea (SU) combination (G2 & G3). Findings also showed significant high frequency of emergency visit and hospitalization in G1 (78.16% & 30.8%) as compared to SU (70.1% & 28.3%, p = 0.001) and DPP-4 (56.6% & 20.4%, p = 0.001). The overall reported effect was z = 2.58, p = 0.001 for ASCVD risk reduction assessment.ConclusionThe study concluded that significant effect of Dipeptidyl peptidase-4 inhibitor on reduction of hospitalization, lipid profile and also ASCVD risk score of type-II diabetes mellitus patients regardless of clinical comorbidities. Also, sulfonylurea combinations have showed significant reduction in LDL and triglycerides values.