Prevalence (%) estimates of diabetes (20-79 years) 2010

The greatest cause of death in people with diabetes is CVD.

But main question asked being if an intensive glycaemic target as compared to the conventional one would result in favourable cardiovascular outcomes

In the past, answers to this question were equivocal

• The UGDP was stopped because of an apparent increased mortality rate with sulfonylureas and the results were dismissed because of statistical biases.

• The results of the UKPDS showed that intensive treatment, as opposed to the conventional approach, was associated with a significant reduction in microvascular-related events. However , in spite of a 16% reduction in the risk of myocardial infarction, borderline statistical significance was achieved (p=0.052).

• Novel data from the UKPDS come from post-trial monitoring for a further 10 years . Notably, between-group differences in HbA1c levels were lost within one year of stopping the randomly assigned therapies. But relative reductions in risk persisted at 10 years for microvascular disease outcomes and significant risk reductions emerged for macrovascular related deaths

...and now, the Megatrials

• ACCORD trial (Action to Control Cardiovascular Risk in Diabetes) was prematurely interrupted because of excess mortality among intensively treated patients .

• VADT (Veteran Administration Diabetes Trial)

• and ADVANCE (Action in Diabetes and Vascular Disease : Preterax and DiamicronMR Controlled Evaluation)

The aim of the glucose arm of ADVANCE trial was to answer the question

whether intensifying glucose control to achieve an A1C of 6.5% would

provide additional benefit in reducing the risk of both micro- and macro-

vascular disease in patients with long-standing T2DM at high risk for

vascular disease.

The hypertension branch of the ADVANCE study investigated the potential

benefits of BP lowering, using the routine administration of an ACEI/diuretic

combination (fixed low-dose combination of perindopril and indapamide vs

placebo) irrespective of initial BP levels or the use of other BP lowering drugs.

Diabetologia (2009) 52:1219–1226

Megatrials in type 2 diabetes.

Stefano Del Prato

Different glucose medications, different outcomes?

Hypoglycaemia: a trigger for CV events?

Glucose control—the longer the disease duration, the smaller the benefit?

Chronic hyperglycemia and cardiovascular disease: cause or link?

Trials relating to glycaemia

EnthusiasEnthusiasmm

TimeTime

UGDPUGDP

UKPDSUKPDS

PROactivePROactive

PROactivePROactive

(Nissen)(Nissen)

ADOPTADOPT

RECORDRECORD

ACCORDACCORD

Adapted from David Matthews, Oxford University, UKPresentation in Paris, April 2008

Adapted from David Matthews, Oxford University, UKPresentation in Paris, April 2008