A goal HbA1c ,7% a level approximating that achieved in the intensive-therapy arms of the DCCT, UKPDS, and PROactive studies is reasonable for many younger patients, depending on their duration of diabetes mellitus, comorbidities, adherence, and personal preferences. Secondary analyses of the DCCT and UKPDS and microvascular data from the ADVANCE trial suggest that even lower HbA1c levels could be beneficial in selected individuals. On the other hand, treatment to achieve a HbA1c ,7% might not be safe or practical for some patients, and factors such as life expectancy, advanced microvascular or macrovascular complications, cognitive function, comorbidi- ties, and risk of hypoglycemia should be considered in every patient before intensifying the therapeutic regimen. Regardless of the degree of glycemic control, treatment of other modifiable risk factors that often accompany diabetes mellitus, such as hypertension and dyslipidemia, results in a substantial reduction in cardiovascular risk. The benefits of a target-driven, multifactorial intervention in patients with type 2 diabetes mellitus were demonstrated in the Steno-2 study.601 Behavioral modification and pharmacological ther- apy targeting hyperglycemia, hypertension, dyslipidemia, and microalbuminuria lowered the risk of cardiovascular disease When the patient and provider elect to use pharmacological therapy to improve glycemic control, several factors should be considered in selecting an agent, including acceptability and safety. Although head-to-head comparisons of different pharmacological regimens are largely lacking, limited evi- dence suggests that all agents are not equivalent. For exam- ple, long-term follow-up from the UKPDS indicates that patients receiving metformin, particularly those who were overweight, had a lower incidence of diabetic complications, MI, and death than those who received insulin plus a sulfonylurea.588 In addition, available information suggests that certain agents lack an acceptable safety profile. 