Type 2 diabetes mellitus (T2DM) and its complications must be managed by using a comprehensive, or global, approach to treatment. The author describes the case of a white man, aged 51 years, with T2DM that was diagnosed 3 years earlier. The patient was obese and had a history of chronic low back pain. He also had diagnosed hypertension, decreased vibratory sensation in the feet, an S4 atrial gallop, trace ankle edema, degenerative joint disease in the knees, and decreased range of motion in the lumbar spine. Other findings at the patient's initial visit included hyperglycemia, microalbuminuria, and lipid abnormalities. Initial treatment included metformin; a nonsteroidal anti-inflammatory drug (naproxen); a thiazolidinedione (rosiglitazone maleate); a thiazide diuretic (hydrochlorothiazide); an angiotensin-converting enzyme inhibitor (enalapril); and lowdose aspirin. At 6-month follow-up, the patient continued to have elevated glycosylated hemoglobin, hypertension, dyslipidemia, and excess weight. Additional treatment strategies consisted of pioglitazone hydrochloride; metformin in combination with the dipeptidyl peptidase IV inhibitor sitagliptin phosphate; a statin (atorvastatin hydrochloride); and enrollment in a diet and exercise program. Results at 12-month followup included a substantial decrease in glycosylated hemoglobin and improved hypertension and dyslipidemia. The patient was successfully treated across the full range of global cardiovascular risk reduction.