Combining insulins with oral antidiabetic agents: effect on hyperglycemic control, markers of cardiovascular risk and disease

Abstract

Patients with type 2 diabetes mellitus (T2DM) have an increased risk of cardiovascular disease (CVD). Unfortunately, several potential barriers exist for CVD risk management in diabetes, including the need for significant lifestyle changes, potential problems with hypoglycemia, weight gain, injection tolerability, treatment complexity with current diabetes therapies and other, unmodifiable factors. Improving glycemic control may impact CVD risk. Treatment of T2DM usually starts with lifestyle changes such as diet and exercise. When these become insufficient, pharmacotherapy is required. Various oral antidiabetic drugs (OADs) are available that reduce hyperglycemia. The first line of therapy is usually metformin, since it does not increase weight and seems to have a beneficial effect on CVD mortality and risk factors. As T2DM progresses, insulin treatment becomes necessary for the majority of patients. The last few years have seen the development of long-acting, rapid-acting, and premixed insulin analog formulations. The treat-to-target algorithms of recent studies combining OADs plus insulin analogs have demonstrated that patients can reach glycemic treatment targets with low risk of hypoglycemia, greater convenience, and--with some analogs--limited weight gain vs conventional insulins. These factors may possibly have a positive influence on CVD risk. Future studies will hopefully elucidate the benefits of this approach.

Keywords: cardiovascular disease; diabetes mellitus; hyperglycemia; insulin; oral antidiabetic drugs; type 2 diabetes.

Figure 1

Improvement in glycemic control reduces risks of long-term complications (Stratton et al 2000).

Figure 2

Mean change in HbA1c (baseline to endpoint) and relative risk for all-day hypoglycemia in comparative trials of basal analogs vs. NPH insulin plus OADs in T2DM. Note: definitions of hypoglycemia vary by study; the glargine ‘relative percentages’ have been derived from the study publications and are not comparable to the relative risk data presented for detemir. ^ap < 0.05 for between treatment difference in change in HbA1c between baseline and end of trial, or in risk of hypoglycaemia (De Vries et al 2007 [in press]). © Reproduced with permission.

Figure 3

Mean change in HbA1c (baseline to endpoint) and relative risk for all-day hypoglycemia in comparative trials of premixed analogs plus OADs in T2DM. Between treatment comparison: ^ap < 0.001; ^bp < 0.01; ^cp < 0.05. ^dCalculated value.