Treatment of type 2 diabetes with combined therapy: what are the pros and cons?

Type 2 diabetes is a progressive syndrome that evolves toward complete insulin deficiency during the patient's life. A stepwise approach for its treatment should be tailored according to the natural course of the disease, including adding insulin when hypoglycemic oral agent failure occurs. Treatment with insulin alone should eventually be considered in a relevant number of cases. Experience has shown the protective effects of insulin on beta-cell survival and function, resulting in more stable metabolic control. On the contrary, treatment with most insulin secretagogues has been associated with increased beta-cell apoptosis, reduced responsiveness to high glucose, and impairment of myocardial function during ischemic conditions. In addition, macrovascular complications are associated with postprandial hyperglycemia, indicating the need for tight glycemic control. Insulin treatment, especially with rapid-acting analogs, has been demonstrated to successfully control postprandial glucose excursions. Finally, a reason for concern with regard to combined therapy is represented by the evidence that polipharmacy reduces compliance to the treatment regimen. This can be particularly relevant in patients with type 2 diabetes usually taking drugs for complications and for concomitant diseases with consequent deterioration not only of metabolic control but also of other conditions. In conclusion, therapy with insulin alone immediately after hypoglycemic oral agent failure may be a useful and safe therapeutic approach in type 2 diabetes.