Metformin is considered to be the first-line drug therapy for the management of Type 2 diabetes. Incretin-based therapies, and especially dipeptidyl peptidase-4 inhibitors, offer new opportunities after failure of metformin. An extensive literature search was performed to analyze all clinical trials combining saxagliptin with metformin. Saxagliptin and metformin may be administered together, either separately or in fixed-dose combination, as saxagliptin added to metformin or as an initial combination. Saxagliptin and metformin are not prone to pharmacokinetic drug–drug interactions and fixed-dose combination allows dosing of one single pill (Kombiglyze® XR) or two pills (Komboglyze®) per day. Both compounds exert pharmacodynamic complementary actions. Their coadministration improves blood glucose control (fasting plasma glucose, postprandial glucose and glycated hemoglobin) more potently than either compound separately. Tolerance is good without hypoglycemia, weight gain and further increase in metformin-related gastrointestinal adverse events. The combination saxagliptin plus metformin may be used as first-line or second-line therapy in the management of Type 2 diabetes.