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Abstract
Background: Miyazaki etal, demonstrated using the hyperinsulinemic, euglycemic clamp that pioglitazone (PIO) enhanced insulin sensitivity in patients (n = 23) with type 2 diabetes (T2D). Although considered the reference method for measuring insulin sensitivity, the clamp is seldom used in large clinical trials because of its complexity. The Homeostasis Model Assessment-Insulin Sensitivity (HOMA-S) and Quantitative Insulin Sensitivity Check Index (QUICKI) are two alternative insulin sensitivity surrogates that correlate with the clamp method and are suitable for use with large study populations.
Study aim: To evaluate the effect of PIO monotherapy and in combination therapy with sulfonylurea (SU) or metformin (MET) on insulin sensitivity as assessed by HOMA-S and QUICKI in a large group of patients (∼1000).
Research design and methods: Patient data from three randomized, double blind, multicenter, parallel group, placebo-controlled registration trials (Studies-001 PIO monotherapy and 010 and 027 combination therapy with SU or MET, respectively) were analyzed for this study. We
evaluated insulin sensitivity for all three studies using HOMA-S and QUICKI.
Results: PIO 15, 30 and 45 mg enhanced HOMA-S compared with baseline (56.9-63.6%, p = 0.0298); (53.7-64.7%, p = 0.0008); (59.0-75.9%, p < 0.0001), respectively. Only the 45 mg dose showed a difference from placebo (p = 0.0025). Similarly, PIO enhanced QUICKI versus baseline (0.290-0.296, p = 0.0026); (0.287-0.299, p = 0.0001); (0.290-0.306, p = 0.0001), respectively. Both the 30 and 45mg doses were different from placebo for QUICKI (p = 0.0005, p < 0.0001). PIO 15 and 30mg plus SU enhanced HOMA-S compared with baseline (58.4–.7%, p = 0.0007; 53.2–68.4%, p < 0.0001) and placebo plus SU (p = 0.0129, p < 0.0001, respectively). Likewise, PIO 15 and 30 mg plus SU enhanced QUICKI versus baseline (0.289-0.300, p = 0.0001; 0.287-0.305, p = 0.0001, respectively). Both doses had different effects from placebo plus SU (p = 0.0001) for QUICKI. PIO 30mg combined with MET enhanced HOMA-S versus baseline (66.2–82.2%, p < 0.0001) and placebo plus MET (p = 0.0002).
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