Intended for healthcare professionals

Rapid response to:


The idolatry of the surrogate

BMJ 2011; 343 doi: (Published 28 December 2011) Cite this as: BMJ 2011;343:d7995

Rapid Response:

Re: The idolatry of the surrogate

Surrogte Markers in T2 Diabetes

Patient oriented hard clinical endpoints are patently of superior significance compared to their surrogate markers. Such endpoints however often take 10 or more years to occur and are fortunately now rarer both of which make studying them harder. The complexity of such a multifactorial disease also makes studying hard endpoints more difficult.
As a GP with a specialist interest in T2 Diabetes over the last 25years I think the authors have selected a poor subject to argue about the dangers of the overuse of surrogate markers. Their article makes no mention of the UKPDS study which did have hard clinical endpoints and emphasised the importance of lowering blood pressure to decrease hard CV endpoints such as MI and death. Other studies such as the HPS with similar hard endpoints have demonstrated how statin therapy also decreases such events.
25 years ago I regularly saw patients with T2D die in their 50’s and 60’s from CV complications. I see such events much less frequently in 2012. This is largely due to the interventions such studies have informed clinicians to make.
If risk factors (aka surrogate markers) have been used in T2D studies then many patients have benefited from such an approach. Microalbuminuria, and it’s detection and treatment, is another important example of a surrogate marker that further along the clinical course has serious renal replacement therapy implications for a proportion of patients. It is treatable and it’s complications largely preventable.
Perhaps significantly all of the above examples largely focus on the prevention of macrovascular diseases in T2D where I believe surrogate markers have been crucial in the advancement of treatments for many patients.
In recent years Glycaemic Control has taken centre stage as the surrogate marker that many studies have focussed on, arguably due to the newer therapies that the drug industry have introduced in this area.
Many such therapies increase circulating insulin which is central to the metabolic syndrome that epitomises T2D. They can also cause dangerous hypoglycaemia. Physiological lowering of blood glucose without hypoglycaemia through improved insulin sensitivity and lower overall insulin levels should be the clinicians goal especially in the early stages of T2D. Ironically endogenous Insulin (B cell function) and Insulin Resistance are the real surrogates we should be bothering about but these are difficult to measure and quantify.
Arguably in relation to Glycaemic Control in T2D we are simply using the wrong surrogates by convenience.

Competing interests: No competing interests

15 January 2012
Ian Dickson
Springwell Medical Centre
39 Ardmillan Terrace, Edinburgh EH11 2JL