Cardiovascular disease and intensive glucose control in type 2 diabetes mellitus: moving practice toward evidence-based strategies

Abstract

Type 2 diabetes mellitus (T2DM) is associated with a high risk of complications, essentially macrovascular events. Surprisingly, the effect of improved glucose control on coronary and cerebrovascular complications and the target level of glycated hemoglobin (HbA(1c)) in this population remains questionable. We here report the results of 4 recently published randomized controlled trials (ACCORD, ADVANCE, VADT, UKPDS post-trial), which did not demonstrate a significant reduction of cardiovascular events in the intensive group compared to the standard group. On the contrary, in ACCORD, the study with the most ambitious goal (HbA(1c) < 6%), the overall and cardiovascular mortality was greater in the intensive group, although the risk of microangiopathic complications, especially nephropathy, was significantly decreased. VADT suggests that one possibility for the lack of observed effect of intensive therapy could be that the cardiovascular benefit is delayed. This contrasts strongly with the long-term postintervention outcomes of UKPDS, which show a persistent benefit of glycemic control during 10 years of post-trial follow-up ('legacy effect'). Therefore, the best way to protect patients with T2DM against coronary and cerebrovascular disease is to target all cardiovascular risk factors as early as possible by an individualized approach.

Trial registration: ClinicalTrials.gov NCT00000620 NCT00032487 NCT00145925.

Keywords: ACCORD; ADVANCE; UKPDS post-trial; VADT; cardiovascular; glycemic control.

Figure 1

Evidence-based guideline for antihyperglycemic treatment in patients with T2DM (adopted from the German Diabetes Association [Deutsche Diabetes Gesellschaft/DDG] based on the data from the ACCORD, ADVANCE, VADT and UKPDS post-trial). ^aReduce HbA_1c level to ≤6.5% from ≤7% might be advantageous but only when: – (severe) hypoglycemia is prevented – weight gain does not occur – use of multiple glucose-lowering drugs (>2) or additional insulin therapy can be avoided HbA_1c should be measured every 3 months. Therapy should be intensified if/when the target level is missed. In contrast, pharmacological dechallenge and ‘step back’ can be performed if the individual HbA_1c remains stable over a longer time.