Therapeutic Use of Metformin in Prediabetes and Diabetes Prevention

Abstract

People with elevated, non-diabetic, levels of blood glucose are at risk of progressing to clinical type 2 diabetes and are commonly termed ‘prediabetic’. The term prediabetes usually refers to high–normal fasting plasma glucose (impaired fasting glucose) and/or plasma glucose 2 h following a 75 g oral glucose tolerance test (impaired glucose tolerance). Current US guidelines consider high–normal HbA1c to also represent a prediabetic state. Individuals with prediabetic levels of dysglycaemia are already at elevated risk of damage to the microvasculature and macrovasculature, resembling the long-term complications of diabetes. Halting or reversing the progressive decline in insulin sensitivity and β-cell function holds the key to achieving prevention of type 2 diabetes in at-risk subjects. Lifestyle interventions aimed at inducing weight loss, pharmacologic treatments (metformin, thiazolidinediones, acarbose, basal insulin and drugs for weight loss) and bariatric surgery have all been shown to reduce the risk of progression to type 2 diabetes in prediabetic subjects. However, lifestyle interventions are difficult for patients to maintain and the weight loss achieved tends to be regained over time. Metformin enhances the action of insulin in liver and skeletal muscle, and its efficacy for delaying or preventing the onset of diabetes has been proven in large, well-designed, randomised trials, such as the Diabetes Prevention Program and other studies. Decades of clinical use have demonstrated that metformin is generally well-tolerated and safe. We have reviewed in detail the evidence base supporting the therapeutic use of metformin for diabetes prevention.

Effect of metformin on semen quality

“…One concern that has been raised relevant to metformin usage is that the consensus panel of diabetes felt that metformin should be considered for diabetes prevention even in non-diabetic individuals (i.e., pre-diabetic or obese individuals). This concern increases the use of this drug by these groups (American Diabetes, 2009;Hostalek, Gwilt, Hildemann, 2015;Manu et al, 2015;McGavock, Dart, Wicklow, 2015).…”

“…One concern that has been raised relevant to metformin usage is that the consensus panel of diabetes felt that metformin should be considered for diabetes prevention even in non-diabetic individuals (i.e., pre-diabetic or obese individuals). This concern increases the use of this drug by these groups (American Diabetes, 2009;Hostalek, Gwilt, Hildemann, 2015;Manu et al, 2015;McGavock, Dart, Wicklow, 2015).Over the last decade, various experimental and clinical studies have linked metformin with sperm function, and thus with male factor infertility Ferreira et al, 2015); however, such direct link has not been established. In this review, we provide fresh and comprehensive understanding of the effect of metformin, as a universally used oral agent, on semen quality (i.e., sperm quantity and quality).…”

Metformin protects renal tubular cells; mechanisms and new concepts

“…Metformin (biguanide) is usually used as the first pharmacological option in pre-diabetic subjects and patients with T2DM mellitus in the Europe, United States, and Australia. Low cost, long-term effect, low risk of hypoglycemia, and ease of utilization are considered significant benefits of metformin compared with other therapies (2). Lower overall mortality and minor risk of serious infection/acidosis are other important benefits of metformin in contrast with medication with insulin and too alternative oral hypoglycemic agents.…”

Multidimensional effects of metformin in patients with type 2 diabetes

“…Данные об умерен-ной эффективности метформина в снижении ИМТ и ре-зистентности к инсулину в краткосрочной перспективе (менее 6 месяцев) подтверждают Hostalek U. и соавт. (2015), акцентируя, что подобные попытки основаны на результатах, наблюдаемых у взрослых [69]. Отметим, что стратегия применения в этом плане метформина, вытекающая из исследования DPP [70], нашла свое от-ражение в инструкции к Глюкофажу только в июле 2016 г.…”