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April 3, 2002

Drug Therapy for Patients With Type 2 Diabetes—Reply

Author Affiliations

Stephen J.LurieMD, PhD, Senior EditorIndividualAuthor

JAMA. 2002;287(13):1645-1646. doi:10.1001/jama.287.13.1645

In Reply: The ancillary DCCT study that Dr Poothullil cites does not present a strong argument against achieving tight glycemic control in diabetic patients when it is associated with weight gain. Although the subjects who gained the most weight did indeed demonstrate higher lipid and blood pressure levels, intensive control in the DCCT was still associated with a trend toward improved cardiovascular outcomes.1 Similarly, sulfonylurea and insulin therapy in the more applicable UKPDS resulted in both weight gain and a modest trend toward decreased macrovascular events.2 Unfortunately, weight gain frequently accompanies the achievement of glycemic control with many therapeutic agents, including sulfonylureas, insulin, and thiazolidinediones. Interestingly, the weight gain associated with the latter appears to be relegated to the more metabolically quiescent peripheral sites, while sparing visceral adipose stores,3 and overall, thiazolidinedione therapy appears to improve cardiovascular risk profiles.4 Thus, I maintain that normalization or near-normalization of blood glucose concentrations should be a primary goal of therapy for most individuals with type 2 diabetes, although admittedly its benefits have been easier to demonstrate for microvascular end points. Weight gain should not dissuade this effort.

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