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No Mortality Reduction in Type 2 Diabetes with Tight Glycemic Control

No effect of tight glycemic control on mortality or major cardiovascular events in long-term follow-up of the ADVANCE trial…. 

The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE study) assessed the effects of routine blood-pressure lowering and strict glucose control in a broad cross section of patients with type 2 diabetes. Over 10 years, patients were followed in ADVANCE-ON, a post-trial follow-up study. No adverse or protective effect was seen whether their blood sugar was tightly controlled or not. However, strict blood pressure control did reduce cardiovascular and overall mortality during the trial.

In the ADVANCE trial, 11,140 patients age 55 year or older, with type 2 diabetes and at least one additional risk factor for cardiovascular disease were enrolled. Patients were randomly assigned to a single-pill, fixed-dose, combination of perindopril (4 mg) and indapamide (1.25 mg) or matching placebo in a 2-by-2 factorial design study. After 6 weeks, participant were randomly assigned to a gliclazide-based intensive glucose-control regimen, targeted to achieve a glycated hemoglobin level of 6.5% or lower, or to standard glucose control, with targets and regimens based on local guidelines. After two years after ADVANCE trial visits, all surviving trial patients were invited to participate in the post-trial follow-up study. 8494 (80%) participants agreed to follow-up.

Researchers concluded that there was no adverse or protective effect whether their blood sugar was tightly controlled or no. The hazard ratio was identical for both outcomes (HR 1.00, 95% CI 0.92 to 1.08). There was significant reduction in the secondary outcome of end-stage renal disease (HR 0.54, 95% CI 0.34 to 0.85, P=0.007). However, no effects on the mortality rate from renal disease were noted. According to Zoungas, the take-home message from her findings is that strict glucose control is important for preventing serious renal complications and doesn’t cause harm in people with established type 2 diabetes. Benefits in blood pressure lowering seen for those who had had intense control with a combination of perindopril and indapamid disappeared by the first post-trial visit. Overall and cardiovascular mortality that were seen in the ADVANCE trial were reduced in ADVANCE-ON. Overall mortality: HR 0.91, 95% CI 0.84 to 0.99, P=0.03. Cardiovascular mortality: HR 0.88, 95% CI 0.77 to 0.99, P=0.04

In summary, among patients with long-standing type 2 diabetes, blood pressure-lowering treatment with perindopril-indapamide resulted in small but significant long-term benefits in respect to mortality from any cause and from cardiovascular causes. On the other hand, strict glycemic control did not provide any long-term benefits with respect to mortality or major macrovascular events.

Practice Pearls:

  • Strict blood pressure control with perindopril-indapamide resulted in small but significant long-term benefits in term of mortality reduction in type 2 diabetes
  • Tight glycemic control showed no mortality reduction in type 2 diabetes
  • Glycemic control in terms of other morbidity in type 2 diabetes is still a significant factor.

Zoungas S, et al “Follow-up of blood-pressure lowering and glucose control in type 2 diabetes” NEngl J Med 2014; DOI: 10.1056/NEJMoa1407963.