The Role of Innovation in Treating Diabetes
September 30, 2010
Stefano Del Prato, MD
Type 2 diabetes is a progressive disease characterized by a continuous loss of beta cell mass and function that manifests in a worsening of blood glucose control. While normoglycemia is the ultimate goal of diabetes management, evidence shows that the majority of patients do not achieve desired glycemic outcomes (i.e., A1C targets proposed by various guidelines and algorithms), and are therefore at risk for developing serious micro- and macrovascular complications. In fact, a recent meta-analysis showed that body mass index, diabetes duration and incidence of severe hypoglycemia correlate positively with a greater risk of cardiovascular (CV) death.
Physicians today have a number of treatment options at their disposal. As with all therapies, however, risks and benefits have to be carefully weighed, and therapies should therefore be personalized and tailored to the individual patient’s needs. Rather than following a “one size fits all” approach, we have proposed a treatment strategy that takes into account A1C and the “ABCD” i.e. Age, Body weight, Complications and Disease duration, to help physicians make the best therapeutic selections for their patients.
In this proposed diabetes management approach, metformin is usually the drug of choice when the A1C is <9% at the time of diagnosis, while insulin with or without metformin should be considered when the A1C is >9%.
Patients who are diagnosed at an advanced age (over 70 years old) and, thus, are more prone to hypoglycemia and comorbidities, might not want to target the stringent A1C goals of 6.5% or 7% currently proposed in the majority of algorithms, but instead strive for an A1C between 7 and 8%. These patients should preferentially use drugs that are not cleared in the kidneys and are not associated with an increased risk for cardiovascular disease. Younger patients (under 40 years) on the other hand, should consider more aggressive A1C targets of <6 % or 6.5%.
Patients who are over their ideal body weight might want to consider therapies that are either weight neutral or lead to weight loss, with additional treatment focus on CV risk factors to address dyslipidemia and hypertension.
Caution in defining the glycemic goal should also be adopted in patients who present with major micro-and/or macrovascular complications. Moreover, in these patients, care should be paid in selecting medications. For instance, thiazolidinediones, or TZDs, are contraindicated in patients with congestive heart failure, and metformin should not be given to patients with renal or heart failure.
Disease duration is another factor that should be taken into account by physicians when choosing the optimal treatment for their patients. As the 10-year follow-up data of the United Kingdom Prospective Diabetes Study (UKPDS) has demonstrated, early intensive diabetes intervention has beneficial effects in preventing micro- and macrovascular complications in the ensuing years. More recently, data from Action to Control Cardiovascular Risk in Diabetes (ACCORD) and the VA Diabetes Trial (VADT) indicate that aggressive treatment in patients with long-standing diabetes may not have a big impact on influencing the development of cardiovascular disease.
Diabetes treatment is a complex exercise, but with the development of newer treatment options, physicians have a lot more tools to find individualized treatment options for their patients. Treatment that may improve glycemic control with low risk of hypoglycemia and without negative effects on body weight may provide a renewed opportunity for effective early intervention. From this point of view, incretin therapies have garnered much attention. This is based, in part, on the expectation that this form of treatment might help protect the beta cell and, therefore, ensure long-term glycemic control.
Stefano Del Prato is Professor of Endocrinology and Metabolism at the School of Medicine, University of Pisa and Chief of the Section of Diabetes, University of Pisa, Italy.
For more related articles, click Diabetes Perspectives.