Intensive Glycemic Control and Cardiovascular Disease: Are There Patients Who May Benefit?

Abstract

Cardiovascular disease (CVD) is the major cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Recent major publications, such as the Action to Control Cardiovascular Risk in Diabetes trial, the Advance in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation trial, and the Veterans Affairs Diabetes Trial, found that intensive glucose control in patients with T2DM did not reduce CVD outcomes. However, in this article, we review observational studies and clinical trials that, on aggregate, indicate how glucose lowering appears to reduce risks of CVD in certain subgroups, but can be harmful in other individuals. Based on available evidence, we suggest that younger patients with a shorter duration of T2DM, without CVD, and with few comorbid conditions may experience the greatest cardiovascular benefit from intensive glucose control. In contrast, more aggressive glucose lowering in older patients with a longer duration of T2DM, a history of CVD, and/or multiple comorbidities does not translate to reduced cardiovascular events, and may cause harm. The target goal and therapeutic strategy for intensive glucose control should be established for each individual after a careful review of his or her medical and psychosocial history, and should not reflect a "one-size-fits-all" approach.

Recent trends in the characteristics of patients prescribed sitagliptin and other oral antihyperglycaemic agents in a large U.S. claims database

“…Patients receiving sitagliptin, and possibly other DPP‐4 inhibitors, may be at higher risk of clinical events simply because of increased risk as a result of baseline characteristics prior to initiation of therapy. At least one previous study highlighted the differences in prognosis associated with varying levels of comorbidities/complications in patients with type 2 diabetes . In that study, patients with higher levels of comorbidities received reduced cardiovascular benefit from intensive glucose control compared with those having lower levels.…”

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“…Prediction of the rate of progression will not only help in stratification of patients according to risk of ESRD but will also direct selection of specific therapies to prevent or delay the onset of ESRD. Such personalized approach are being developed in other fields (40–42). …”

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“…CHD is a main cause of morbidity and mortality in patients with T2DM [2]. Diabetes mellitus is a chronic disease with multiple metabolic abnormalities including insulin resistance and increased levels of biomarkers of inflammation and oxidative stress [3].…”