Effects of pioglitazone and metformin on β-cell function in nondiabetic subjects at high risk for type 2 diabetes

Neda Rasouli, Philip A. Kern, E. Albert Reece, Steven C. Elbein

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Thiazolidinediones (TZDs) and metformin decreased the incidence of diabetes in subjects at risk for developing diabetes and improved peripheral or hepatic insulin sensitivity, respectively. Whether they also directly improved β-cell function is not clear. In vitro studies showed improved β-cell function in response to TZDs and metformin; however, the effects of TZDs or metformin on β-cell function in humans are still uncertain. We hypothesized that both TZDs and metformin directly affect β-cell function. We evaluated β-cell function and insulin sensitivity (SI) in subjects with impaired glucose tolerance or a history of gestational diabetes using oral and intravenous glucose tolerance tests in addition to the glucose-potentiated arginine stimulation test. In contrast to metformin, pioglitazone improved SI, glucose tolerance, and insulin-independent glucose disposal [glucose effectiveness (SG)]. Neither pioglitazone nor metformin significantly improved β-cell compensation for insulin resistance [disposition index (DI)], but the change in DI significantly correlated with baseline SI. Insulin secretion in response to arginine at maximally potentiating glucose levels (AIRmax) tended to increase after metformin and to decrease after pioglitazone; however, when adjusted for S I, the changes were not significant. Our results demonstrate that, in nondiabetic subjects at risk for diabetes, pioglitazone, but not metformin, significantly improved glucose tolerance by improving SI and S G. We did not find any evidence that either pioglitazone or metformin improved β-cell function. Improved β-cell compensation was observed primarily in the subgroup of subjects that had the lowest SI at baseline.

Original languageEnglish
Pages (from-to)E359-E365
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number1
StatePublished - Jan 2007


  • Insulin sensitizer
  • Prediabetes

ASJC Scopus subject areas

  • General Medicine


Dive into the research topics of 'Effects of pioglitazone and metformin on β-cell function in nondiabetic subjects at high risk for type 2 diabetes'. Together they form a unique fingerprint.

Cite this