RESEARCH
METFORMIN: THE UNSUNG HERO DRUG By
Jack Osborn Marissa McCollum
Metformin is a commonly prescribed drug used to treat high blood sugar most commonly in diabetic patients as an antihyperglycemic biguanide, referring to a class of drugs used to treat type 2 diabetes. These drugs function by decreasing hepatic glucose primarily by inhibiting the body’s metabolic process of producing sugar, known as gluconeogenesis. While the drug has been widely distributed for over two decades as a diabetic drug, having received FDA approval in October of 1998, only recently has evidence provided support for the use and implementation of the drug to both improve insulin sensitivity and limit carcinogenesis in otherwise healthy individuals. Thus, the drug shows new potential in delivering anti-cancer benefits that can be of use to everyone in society. Today, the drug is largely distributed as 1,1-dimethylbiguanide hydrochloride and has recently been shown to function
though previously undescribed mechanisms, including pathways that may offer overarching benefits to health. Beyond its capacity for diabetes treatment, increasing data has come to light surrounding metformin’s implications in regulating and improving gut health. More than one third of all Americans suffer from metabolic syndrome, an overarching disease state used to describe a series of inflammatory conditions such as elevated blood sugar, high blood pressure, and gut dysbiosis; the gut microbiome has been shown to play a crucial role in metabolic syndrome pathogenesis. Due to metformin’s therapeutic capacity to boost gut health, the drug shows promise in improving an otherwise healthy individual’s metabolic state, critical to longevity and a healthy life. Type 2 diabetes is characterized in its simplest terms as an inability or resistance to release insulin
in response to carbohydrates, resulting in elevating blood sugar. Insulin, a hormone normally released by the pancreas, serves to allow glucose to pass from blood into cells for use in metabolism. Since its initial administration, metformin has been shown to chronically improve insulin sensitivity and thereby mitigate a diabetic’s fasting blood sugar levels. Specifically, metformin both directly and indirectly upregulates the AMPK pathway, an essential control system of many cellular processes, including glucose production in the liver (see Figure I). In a cell treated with metformin, cellular respiration is suppressed, and glucose biosynthesis (gluconeogenesis) is inhibited. Metformin also indirectly mediates several other metabolic pathways that increase insulin sensitivity, resulting in lower overall blood sugar and healthier metabolism of consumed sugars. Importantly, metformin does not
spring 2021 || 19
