What is the potential role of transcription factor 7–like 2 (TCF7L2) in the treatment of type 2 diabetes mellitus?

Updated: Dec 14, 2018
  • Author: Ali Torkamani, PhD; Chief Editor: Keith K Vaux, MD  more...
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Researchers are also exploring whether TCF7L2 variants might serve as markers for tailoring customized therapeutic regimens. For example, DPP4 is a peptidase that degrades incretins such as GLP-1. [27] DPP4 inhibitors enhance incretin-stimulated insulin secretion and inhibit glucagon release, thereby helping to normalize blood glucose levels. If a negative influence on incretin secretion is confirmed as a major pathologic axis in TCF7L2 -driven type 2 diabetes, DPP4 inhibitors could potentially serve as a counterbalance and reverse the effects of TCF7L2 variants on incretin levels. [27] TCF7L2 polymorphisms have been associated with variation in the response to sulfonylurea treatment, but these effects are likely too modest to guide care. [28, 29]

Obviously, the clinical utility of TCF7L2 variants is associated with some caveats. First, the specific type 2 diabetes risk variants of TCF7L2 vary from population to population. [30] Similar effect sizes have been observed in a number of ethnic groups for the most commonly studied TCF7L2 variants, but the research must be expanded further beyond nonwhite populations. Second, although the effect sizes of TCF7L2 variants are relatively large, a much more accurate picture of risk stratification and therapeutic personalization would be informed by a larger collection of predisposition genes rather than TCF7L2 alone. 

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