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These studies suggest that low-dose metformin can improve glycemic control, reduce the risk of developing type 2 diabetes, and provide benefits in conditions like PCOS, nonalcoholic fatty liver disease, and peripheral vascular disease, while also potentially enhancing cancer immunotherapy response.
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The CANOE trial demonstrated that a low-dose combination of metformin (500 mg) and rosiglitazone (2 mg) significantly reduced the incidence of type 2 diabetes in patients with impaired glucose tolerance. Over a median of 3.9 years, the combination therapy group had a 66% relative risk reduction in developing diabetes compared to the placebo group. Additionally, 80% of patients in the treatment group regressed to normal glucose tolerance, highlighting the efficacy of low-dose metformin in diabetes prevention.
In patients with type 2 diabetes undergoing maintenance hemodialysis, very-low-dose metformin (250-500 mg/day) improved glycemic control without causing lactic acidosis. The study showed a significant reduction in glycemic variability and glycoalbumin levels, indicating that low-dose metformin can be safely used in this high-risk population when appropriately monitored.
A study on prediabetic patients treated with 1500 mg/day of metformin for 15 weeks found that patients achieved therapeutic serum concentrations of the drug, which correlated positively with body weight. This suggests that low-dose metformin can effectively manage prediabetes and achieve desired glycemic effects.
A phase II trial investigated the combination of low-dose metformin with temozolomide in patients with recurrent or refractory glioblastoma. Although the combination was well-tolerated, it did not significantly improve progression-free survival or overall survival compared to temozolomide alone.
In a phase II clinical trial, low-dose metformin (250 mg/day) reprogrammed the tumor immune microenvironment in esophageal squamous cell carcinoma. The treatment increased the infiltration of cytotoxic T lymphocytes and tumor-suppressive macrophages, suggesting potential benefits in enhancing anticancer immunity.
A study comparing low-dose metformin (1000 mg/day) with spironolactone (50 mg/day) and their combination in women with PCOS found that the combination therapy was superior. It significantly improved menstrual cycle regularity, reduced androgen levels, and improved insulin sensitivity more effectively than either drug alone.
In a randomized study, low-dose metformin (1000 mg/day) combined with dietary treatment was more effective than diet alone in reducing liver steatosis and improving metabolic parameters in patients with NAFLD. The metformin group showed significant improvements in insulin resistance and a reduction in the prevalence of metabolic syndrome.
A study on patients with symptomatic peripheral vascular disease treated with low-dose metformin (500 mg twice daily) showed improvements in arterial function and exercise capacity. The treatment also reduced levels of fibrinolytic system components, indicating potential cardiovascular benefits.
In non-obese type 2 diabetic patients, low-dose metformin (500-750 mg/day) was more effective than acarbose in improving glycemic control. The study found significant reductions in fasting plasma glucose and HbA1c levels with metformin treatment.
Low-dose metformin has demonstrated efficacy and safety across various conditions, including diabetes prevention, cancer treatment, PCOS, NAFLD, and PVD. Its ability to improve glycemic control, enhance anticancer immunity, and provide cardiovascular benefits makes it a versatile therapeutic option. However, the specific dosage and patient population should be carefully considered to maximize benefits and minimize risks.
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