Metabolism: clinical and experimental
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Randomized Controlled Trial Multicenter Study
Effects of sitagliptin or metformin added to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients.
The aim of the study was to compare the effects of the addition of sitagliptin or metformin to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients on body weight, glycemic control, beta-cell function, insulin resistance, and inflammatory state parameters. One hundred fifty-one patients with uncontrolled type 2 diabetes mellitus (glycated hemoglobin [HbA(1c)] >7.5%) in therapy with pioglitazone 30 mg/d were enrolled in this study. We randomized patients to take pioglitazone 30 mg plus sitagliptin 100 mg once a day, or pioglitazone 15 mg plus metformin 850 mg twice a day. ⋯ A significant decrease of high-sensitivity C-reactive protein value was obtained in both groups without any significant differences between the 2 groups. There was a significant correlation between HOMA-IR decrease and ADN increase, and between HOMA-IR decrease and R and TNF-alpha decrease in pioglitazone plus metformin group after the treatment. The addition of both sitagliptin or metformin to pioglitazone gave an improvement of HbA(1c), FPG, and PPG; but metformin led also to a decrease of body weight and to a faster and better improvement of insulin resistance and inflammatory state parameters, even if sitagliptin produced a better protection of beta-cell function.
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Pioglitazone is prescribed to improve insulin sensitivity in type 2 diabetes mellitus patients and has been discussed as a therapy for metabolic syndrome. Pioglitazone and other thiazolidinediones are associated with fluid retention and edema that may exacerbate existing or developing congestive heart failure, which is often present in these patients. Using a nonhuman primate model, our aims were to evaluate (1) whether fluid shifts were detectable in normoglycemic monkeys, (2) which fluid compartment changed, and (3) whether fluid retention was dose dependent. ⋯ Significant trends toward increases in interstitial fluid and extracellular water with increasing dose were apparent. Pioglitazone effectively improved metabolic status by significantly decreasing fasting glucose and triglycerides and increasing adiponectin. We conclude that thiazolidinedione-related plasma volume expansion occurs in nondiabetic primates and that fluid retention is detectable when compartments are directly measured.