Do the means justify the ends?

Diabetes management focuses on achieving control over blood sugar levels, but two recently concluded clinical trials show that the means of achieving this control are as important as the end result desired. The results of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Study Group as well as the Action in Diabetes and Vascular Disease (ADVANCE) Collaborative Group were presented at the 68th Scientific Session of the American Diabetes Association (ADA).

Both trials provide somewhat different results regarding blood sugar control and cardiovascular events for patients with type 2 diabetes. These two studies (reports of which are carried in the New England Journal of Medicine's June 12 edition and also online at www.nejm.org) tested the premise that using combinations of drugs to achieve stringent glucose control would improve outcomes in patients with type 2 diabetes mellitus. The studies, which used different drugs, found that, contrary to expectations, the tight control achieved did not reduce the risk of complications. In fact, one part of the ACCORD study had to be discontinued prematurely due to an association with a higher risk of death. The ADVANCE study's findings indicated that its strategy may reduce the risk of worsening kidney function at the cost of an excess risk of low blood sugar events.

These negative results set the stage for a debate on this subject and throw up a number of questions. An NEJM editorial cites recommendations suggesting the adoption of 'individualised' goals for certain populations, noting that less intensive glycemic goals may be indicated in patients with severe or frequent hypoglycemia. On the basis of the data presented, special consideration may now need to be given to high-risk patients with multiple risk factors and heart disease.

Clinicians and pharmaceutical companies in India will no doubt be following this debate very closely as India has been tipped to become the diabetes capital of the world. In fact, at the same conference, Piramal Life Sciences Limited (PLSL) made an oral presentation of preclinical pharmacological data pertaining to a novel, orally active glucose-lowering compound, P1736 for the same class of patients.

There is also the fact that conventional disease management is based on attempts to reduce risk factors in order to reduce disease, but these clinical trails show that the strategies used to achieve risk factors control may result in increasing risk to other conditions. This has been observed across therapeutic segments. The ACCORD-ADVANCE study results may just set the stage for a fresh look at evaluating clinical trial strategies.

Viveka Roychowdhury
viveka.r@expressindia.com