November 2002 · Vol. 51, No. 11
LETTERS to the Editor
Are thiazolidinediones first-line agents?
To the editor:
In the “Clinical Inquiries” section of the May 2002 issue of the Journal of Family Practice, Drs Culhane and Graves1 summarized their opinion on the “glitazones” by saying that the “… thiazolidinediones are not generally considered for first-line therapy.” They followed that immediately with, “These agents may be most beneficial in patients with insulin resistance ….” The problem is that all individuals with type 2 diabetes have insulin resistance. Insulin resistance is the underlying problem. In medicine we try to always treat the underlying problem and not just symptoms. Elevated glucose and insulin levels are mere symptoms of the problem, and using sulfonylureas and insulin merely treats symptoms. Metformin also treats only the symptom of hyperglycemia. Therefore, the thiazolidinediones should be used as the very first-line agent (after exercise and diet) in type 2 diabetes unless contraindicated. All other agents are second-line therapy. Although insurance companies may agree with Drs Culhane and Graves because the thiazolidinediones are more expensive, in this case the best medical practice is clear cut.
David L. Weldy, MD, PhD
Department of Family Practice
Northeast Ohio Universities College of Medicine
Dr Culhane responds:
I thank Dr Weldy for his comments regarding the role of thiazolidinediones in the treatment of diabetes mellitus. It is true that most patients with type 2 diabetes mellitus are insulin resistant and that sulfonylureas and insulin do not treat the underlying insulin resistance seen in these individuals. However, these agents do treat the hyperglycemia and offer a relatively safe and inexpensive approach to the treatment of type 2 diabetes mellitus. In addition, the sulfonylureas, insulin, and metformin are the only agents proven to decrease microvascular complications in patients with type 2 diabetes mellitus.2 Also, metformin is the only medication that has been shown to reduce macrovascular complications and mortality in obese patients with type 2 diabetes mellitus.3 Although the primary mechanism of action of the thiazolidinediones is to improve insulin sensitivity, there are no randomized controlled trials demonstrating that their novel mechanism of action leads to a reduction in morbidity and mortality. In addition, the thiazolidinediones cost considerably more than metformin and sulfonylureas, and liver enzymes of patients on thiazolidinediones must be monitored every 2 months because of the potential risk of hepatotoxicity. Therefore, based on available evidence, metformin should be used as initial drug treatment in obese patients with type 2 diabetes mellitus. In nonobese patients, sulfonylureas or metformin may be used first-line treatment and thiazolidinediones should be reserved for patients who cannot tolerate or have a contraindication to sulfonylureas or metformin.
Nicole Sparano Culhane, PharmD, BCPS
Nesbitt School of Pharmacy, Wilkes University
- Culhane NS,
How beneficial are thiazolidinediones for diabetes mellitus? J Fam Pract 2002;51:424.
- Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837–53.
- Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854–65.
The Journal of Family Practice ©2002 Quadrant HealthCom Inc.