Metformin in the context of Oral administration

Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin or the cells of the body becoming unresponsive to insulin's effects. Classic symptoms include the three Ps: polydipsia (excessive thirst), polyuria (excessive urination), polyphagia (excessive hunger), weight loss, and blurred vision. If left untreated, the disease can lead to various health complications, including disorders of the cardiovascular system, eye, kidney, and nerves. Diabetes accounts for approximately 4.2 million deaths every year, with an estimated 1.5 million caused by either untreated or poorly treated diabetes.

The major types of diabetes are type 1 and type 2. The most common treatment for type 1 is insulin replacement therapy (insulin injections), while anti-diabetic medications (such as metformin and semaglutide or tirzepatide) and lifestyle modifications can be used to manage type 2. Gestational diabetes, a form that sometimes arises during pregnancy, normally resolves shortly after delivery. Type 1 diabetes is an autoimmune condition where the body's immune system attacks the beta cells (β-cell) in the pancreas, preventing the production of insulin. This condition is typically present from birth or develops early in life. Type 2 diabetes occurs when the body becomes resistant to insulin, meaning the cells do not respond effectively to it, and thus, glucose remains in the bloodstream instead of being absorbed by the cells. Additionally, diabetes can also result from other specific causes, such as genetic conditions (monogenic diabetes syndromes like neonatal diabetes and maturity-onset diabetes of the young), diseases affecting the pancreas (such as pancreatitis), or the use of certain medications and chemicals (such as glucocorticoids, other specific drugs and after organ transplantation).

Bone marrow adipose tissue (BMAT), also referred to as marrow adipose tissue (MAT), is a type of adipose tissue (fat deposit) found within the bone marrow. BMAT increases in conditions associated with low bone density, such as osteoporosis, anorexia nervosa and caloric restriction, and skeletal weightlessness such as that occurring during spaceflight. It has also been linked to certain anti-diabetic therapies.

Conversely, BMAT decreases in conditions such as anaemia, leukaemia, and hypertensive heart failure; in response to hormones including oestrogen, leptin, and growth hormone; with exercise-induced weight loss or bariatric surgery; following chronic cold exposure; and after treatment with pharmacological agents such as bisphosphonates, teriparatide, and metformin.

Vitamin B₁₂ deficiency, also known as cobalamin deficiency, is the medical condition in which the blood and tissue have a lower than normal level of vitamin B₁₂. Symptoms can vary from none to severe. Mild deficiency may have few or absent symptoms. In moderate deficiency, feeling tired, headaches, soreness of the tongue, mouth ulcers, breathlessness, feeling faint, rapid heartbeat, low blood pressure, pallor, hair loss, decreased ability to think and severe joint pain and the beginning of neurological symptoms, including abnormal sensations such as pins and needles, numbness and tinnitus may occur. Severe deficiency may include symptoms of reduced heart function as well as more severe neurological symptoms, including changes in reflexes, poor muscle function, memory problems, blurred vision, irritability, ataxia, decreased smell and taste, decreased level of consciousness, depression, anxiety, guilt and psychosis. If left untreated, some of these changes can become permanent. Temporary infertility, reversible with treatment, may occur. A late finding type of anemia known as megaloblastic anemia is often but not always present. In exclusively breastfed infants of vegan mothers, undetected and untreated deficiency can lead to poor growth, poor development, and difficulties with movement.

Causes are usually related to conditions that give rise to malabsorption of vitamin B₁₂ particularly autoimmune gastritis in pernicious anemia. Other conditions giving rise to malabsorption include surgical removal of the stomach, chronic inflammation of the pancreas, intestinal parasites, certain medications such as long-term use of proton pump inhibitors, H2-receptor blockers, and metformin, and some genetic disorders.