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These studies suggest metformin has multiple benefits including reducing abdominal aortic aneurysm growth, lowering the risk of heart failure and non-Hodgkin lymphoma, and providing various protective effects, without increasing the risk of lactic acidosis.
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Metformin is a widely prescribed oral antidiabetic medication primarily used to manage type 2 diabetes mellitus (T2DM). It is known for its efficacy in lowering blood glucose levels by improving insulin sensitivity and reducing hepatic glucose production. However, recent studies have highlighted several non-glycemic benefits of metformin, suggesting potential applications beyond diabetes management.
Recent research has shown that metformin may significantly reduce the growth of abdominal aortic aneurysms (AAA). A meta-analysis involving 153,553 patients found that those prescribed metformin experienced a slower AAA growth rate (0.9 mm/year) compared to those not on the medication (1.8 mm/year). Additionally, metformin was associated with a reduced risk of AAA-related events, such as rupture or the need for surgical repair, indicating its potential protective effects in vascular health.
Metformin has also been linked to cardiovascular benefits, particularly in patients with T2DM and hypertension. A study demonstrated that long-term metformin use was associated with a lower incidence of new-onset symptomatic heart failure with preserved ejection fraction (HFpEF). Patients on metformin showed significant improvements in left ventricular diastolic function and hypertrophy, suggesting that metformin may help delay the progression of HFpEF.
Another notable benefit of metformin is its potential to reduce the risk of certain cancers. A large cohort study involving over 600,000 patients with T2DM found that metformin users had a lower incidence of non-Hodgkin lymphoma (NHL) compared to those on other antidiabetic medications. The hazard ratio for metformin initiators was significantly lower, indicating a protective effect against NHL.
Metformin's benefits extend beyond glycemic control. It has been shown to have weight-stabilizing, renoprotective, neuroprotective, cardiovascular protective, and antineoplastic effects. Additionally, metformin's anti-inflammatory and antioxidant properties make it a promising adjunct therapy for infectious diseases, including tuberculosis, viral hepatitis, and COVID-19. These non-glycemic effects highlight metformin's potential for repurposing in various therapeutic areas.
Adherence to metformin therapy is crucial for achieving optimal glycemic control. A study examining metformin adherence found that patients with higher adherence (medication possession ratio ≥ 0.8) had significantly lower glycated hemoglobin (HbA1c) levels. However, disparities in adherence were noted among different ethnic groups, with Māori patients showing lower adherence rates compared to New Zealand Europeans, underscoring the need for targeted interventions to improve adherence.
Concerns about metformin-induced lactic acidosis have been prevalent, especially in patients with chronic hypoxemic conditions. However, a comprehensive review of 347 studies found no evidence of increased risk of lactic acidosis in metformin users compared to those on other glucose-lowering therapies. The incidence of lactic acidosis was extremely low, suggesting that metformin is safe for use in a broad range of patients.
Metformin, while primarily used for managing T2DM, offers a range of non-glycemic benefits, including reduced AAA growth, cardiovascular protection, and lower cancer risk. Its safety profile remains robust, with minimal risk of lactic acidosis. These findings support the potential for metformin's repurposing in various therapeutic applications, warranting further research and randomized trials to explore its full benefits.
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