Rosiglitazone is a potent oral antidiabetic agent of the thiazolidinedione class that works through activation of the peroxisome proliferator‐activated nuclear receptor. It improves insulin sensitivity in peripheral tissues and effectively lowers blood glucose in patients with type 2 diabetes. Metformin is a dimethyl‐biguanide, also used in type 2 diabetes, that lowers fasting blood glucose primarily by decreasing hepatic glucose output. Rosiglitazone and metformin reduce plasma glucose concentrations via different mechanisms and thus could potentially be used in combination to optimize glycemic control. This study evaluated the effects of the coadministration of these two agents on the pharmacokinetics of both rosiglitazone and metformin. Sixteen male volunteers (22–55 years old) received oral metformin (500 mg every 12 hours), rosiglitazone (2 mg every 12 hours), or the combination each for 4 days. Plasma collected on day 4 of each regimen was assayed for rosiglitazone and metformin concentrations. Oral doses of rosiglitazone and metformin were safe and well tolerated when administered alone or in combination. There were no clinically significant episodes of hypoglycemia or increased blood lactic acid levels following treatment with any regimen. Coadministration of rosiglitazone and metformin had no significant effects on the steady‐state pharmacokinetics (AUC(0‐12h), Cmax, tmax, or t1/2) of either drug. The authors conclude that rosiglitazone can be safely administered with metformin and, due to the different mechanisms of action of these agents, may offer a therapeutic advantage in patients with type 2 diabetes mellitus.
Aim: To establish a simple risk score for identifying individuals at high risk of developing Type 2 Diabetes Mellitus (T2DM) in Qatar, based on easy-to-obtain variables.
Materials and Methods: A cross sectional sample of 2000 individuals from Qatar BioBank, obtained for the development cohort, was evaluated using the Least Absolute Shrinkage and Selection Operator (LASSO) for feature selection along with logistic regression to determine the predictive variables for the risk of T2DM along with impaired glucose metabolism (IGM). Complex machine learning analyses were performed for comparative purposes. Another sample of 1000 participants was subsequently obtained for external validation of the developed models. Several existing scoring models screening for T2DM were evaluated and compared to the model proposed by this study.
Results: 1660 participants were included in the analysis which showed that age, gender, waist-to-hip-ratio, history of hypertension (HTN), history of hypercholesteremia (HCL) and levels of educational were statistically associated with the risk of T2DM and constituted the Qatari diabetes risk score (QDRISK). In addition to the 6 aforementioned variables constituting the QDRISK, the IGM model showed that BMI was statistically significant. The QDRISK performed well with an area under the curve (AUC) 0.870 (95%CI 0.843, 0.896) in the development and 0.815 (95% CI: 0.765, 0.864) and external validation cohort. Compared to the majority of evaluated scores, the QDRISK showed overall better accuracy and calibration. The IGM model performed moderately high with AUC 0.796 (95% CI: 0.774, 0.819) in the development cohort and 0.774 (95% CI: 0.740, 0.809) in the external validation cohort.
Conclusions: Our study investigated risk factors for developing T2DM as well as IGM and developed Qatari-specific risk scores based on demographic and anthropometric factors to identify high risk individuals. This simple, cost-effective and convenient tool can guide the development of a nationwide primary prevention program in Qatar.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.