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Browsing by Subject "metformin"
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Item How effective is metformin in reducing cardiovascular risks in adults with T2DM?(Wolters Kluwer, 2021-10) Ahsani, Navid; Williams, Ashley P.; Family Medicine, School of MedicineItem A pharmacodynamic study of sirolimus and metformin in patients with advanced solid tumors(Springer, 2018-08) Sehdev, Amikar; Karrison, Theodore; Zha, Yuanyuan; Janisch, Linda; Turcich, Michelle; Cohen, Ezra E. W.; Maitland, Michael; Polite, Blase N.; Gajewski, Thomas F.; Salgia, Ravi; Pinto, Navin; Bissonnette, Marc B.; Fleming, Gini F.; Ratain, Mark J.; Sharma, Manish R.; Medicine, School of MedicineBackground Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor. Metformin may potentiate mTOR inhibition by sirolimus while mitigating its adverse effects. We conducted a pilot study to test this hypothesis. Methods Patients with advanced solid tumor were treated with sirolimus for 7 days followed by randomization to either sirolimus with metformin (Arm A) or sirolimus (Arm B) until day 21. From day 22 onwards, all patients received sirolimus and metformin. The primary aim was to compare the change in phospho-p70S6K (pp70S6K) in peripheral blood mononuclear cells (PBMC) from day 8 to day 22 using a two-sample t test. Secondary aims were objective response rate, toxicity, and other serum pharmacodynamic biomarkers (e.g., fasting glucose, triglycerides, insulin, C-peptide, IGF-1, IGF-1R, IGF-BP, and leptin). Results 24 patients were enrolled, with 18 evaluable for the primary endpoint. There was no significant difference in mean change in pp70S6K in arm A vs. arm B (− 0.12 vs. − 0.16; P = 0.64). Similarly, there were no significant differences in other serum pharmacodynamic biomarkers. There were no partial responses. There were no dose-limiting or unexpected toxicities. Conclusions Adding metformin to sirolimus, although well tolerated, was not associated with significant changes in pp70S6K in PBMC or other serum pharmacodynamic biomarkers. Impact: Combining metformin with sirolimus did not improve mTOR inhibition.Item Slowing Disease Progression in Type 2 Diabetes: Latest Advances(Association of Kenya Physicians, 2007) Otieno, C. F.; Association of Kenya Physicians Scientific Conference (11th : Mar. 2007 : Eldoret, Kenya)Background: Largest head-to-head, double-blind study of metformin, glyburide and rosiglitazone (N = 4,360). Primary objective: To compare the durability of glycemic control using rosiglitazone versus metformin or glyburide as initial monotherapy in patients with recently diagnosed type 2 diabetes. Design: Double-blind, randomized, controlled trial. Inclusion criteria: Type 2 diabetes ≤ 3 years, drug-naive, male and female, aged 30–75 years, FPG 126–180 mg/dl (7–10 mmol/l). Exclusion criteria: Previous use of glucose-lowering therapy, women of child-bearing potential, significant hepatic disease, renal impairment, unstable or severe angina, known CHF (NYHA Class I–IV), uncontrolled hypertension. Treatment duration: Treatment period: 4 to 6 years. Median duration of treatment: 4 years (rosiglitazone and metformin); 3.3 years (glyburide). Interventions: Rosiglitazone, metformin, glyburide.