Background: The benefits of combination therapies in the management of type 2 diabetes arernwell-documented, while the comparative glycemic control and cardiovascular outcomes amongrnthe different combination options have not been studied well. The study aimed to comparernglycemic control and risk of cardiovascular outcomes of metformin-insulin versus metforminsulfonylurearncombinationrntherapiesrninrntypern2 diabetesrnmellitus.rnrnMethod: A comparative cross-sectional study was conducted in five tertiary level hospitals inrnAddis Ababa, Ethiopia. About 321 patients with type 2 diabetes mellitus who were onrncontinuous treatment follow up on either metformin-insulin or metformin-sulfonylurearncombination therapy were enrolled. Participants were interviewed and their medical records werernreviewed to investigate medication efficacy, safety, and adherence. The primary outcomernmeasure was glycemic control (reduction in glycated hemoglobin A1c) and the secondaryrnoutcome measures were composite cardiovascular outcomes (myocardial infarction, stroke, heartrnfailure), microvascular complications (diabetic neuropathy, retinopathy, and nephropathy),rntreatment-emergent adverse events, changes in bodyweight, fasting blood sugar, systolic bloodrnpressure, diastolic blood pressure and lipid profiles (low-density lipoprotein-cholesterol, highdensityrnlipoprotein-cholesterol,rnand triglycerides).rnrnResults: Of the total participants enrolled, 162 (50.5%) were those who received metformininsulinrnrnand 159 (49.5%) metformin-sulfonylurea combination therapies for a median of 48rnmonths follow-up. Reduction of HbA1c was not different between the two groups, p = .912, withrnmean Â± SD of -1.04 Â± .96 % versus -1.02 Â± 1.03%, respectively. Patients who receivedrnmetformin-sulfonylurea are 4.3 times more likely to have achieved target HbA1c level comparedrnto those who received metformin-insulin, p < .001 (AOR=4.31 [95% CI 1.79-10.32]). Risk ofrncomposite cardiovascular outcomes was higher in metformin-insulin group (40.5% versusrn34.0%), p = .021. Co-morbidities, body mass index, systolic blood pressure, and HbA1c had arnsignificant association with composite cardiovascular outcomes. Reductions of bodyweight, lipidrnprofiles, and microvascular complications were different between the two groups, p < .05. rnConclusion: High proportion of patients who received metformin-sulfonylurea achieved targetrnHbA1c level and had less composite cardiovascular outcomes compared to those who received metformin-insulin. However, these findings have to be confirmed with randomized control trialsrnto determine risks associated with insulin use, while efficacy is maintained as second-linerntreatment in patients with type 2 diabetes mellitus.