Metformin has been designated as one of the most crucial first-line therapeutic agents in the management of type 2 diabetes mellitus. Primarily being an antihyperglycemic agent, metformin also has a plethora of pleiotropic effects on various systems and processes. It acts majorly by activating AMPK (Adenosine Monophosphate-Activated Protein Kinase) in the cells and reducing glucose output from the liver. It also decreases advanced glycation end products and reactive oxygen species production in the endothelium apart from regulating the glucose and lipid metabolism in the cardiomyocytes, hence minimizing the cardiovascular risks. Its anticancer, antiproliferative and apoptosis-inducing effects on malignant cells might prove instrumental in the malignancy of organs like the breast, kidney, brain, ovary, lung, and endometrium. Preclinical studies have also shown some evidence of metformin’s neuroprotective role in Parkinson’s disease, Alzheimer’s disease, multiple sclerosis and Huntington’s disease. Metformin exerts its pleiotropic effects through varied pathways of intracellular signalling and exact mechanism in the majority of them remains yet to be clearly defined. This article has extensively reviewed the therapeutic benefits of metformin and the details of its mechanism for a molecule of boon in various conditions like diabetes, prediabetes, obesity, polycystic ovarian disease, metabolic derangement in HIV, various cancers and aging.

Cardiovascular diseases and type 2 diabetes mellitus (T2DM) have risen steadily worldwide, particularly in low-income and developing countries. In the last hundred years, deaths caused by cardiovascular diseases increased rapidly to 35–40%, becoming the most common cause of mortality worldwide. Cardiovascular disease is the leading cause of morbidity and mortality in type 2 diabetes mellitus (T2DM), which is aggravated by hypertension. Hypertension and diabetes are closely interlinked since they have similar risk factors such as endothelial dysfunction, vascular inflammation, arterial remodeling, atherosclerosis, dyslipidemia, and obesity. Patients with high blood pressure often show insulin resistance and have a higher risk of developing diabetes than normotensive individuals. It has been observed that over the last 30 years, the prevalence of insulin resistance (IR) has increased significantly. Accordingly, hypertension and insulin resistance are strongly related to an increased risk of impaired glucose tolerance, diabetes, cardiovascular diseases (CVD), and endocrine disorders. Common mechanisms, for instance, upregulation of the renin–angiotensin–aldosterone system, oxidative stress, inflammation, and activation of the immune system, possibly have a role in the association between diabetes and hypertension. Altogether these abnormalities significantly increase the risk of developing type 2 diabetes.

Insulin resistance is a critical pathophysiological process in the onset and advancement of type 2 diabetes mellitus. It is well-recognized that alterations in the metabolism of lipids and aberrant fat buildup effectively trigger the development of resistance to insulin. Adjusting one’s eating habits and managing weight appropriately are crucial for treating, controlling, and reducing the risk of T2DM because obesity and a lack of physical exercise are the primary factors responsible for the worldwide rise in T2DM. Omega-3 fatty acid is one of the polyunsaturated fatty acids (PUFA) that include long-chain omega-3 fatty acids such as eicosapentaenoic acid and docosahexaenoic acid, commonly found in fish oils. Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs; 3 and 6 PUFAs) are essential for human health because they serve as metabolic precursors of eicosanoids, a class of signaling molecules that are essential for controlling a body’s inflammation. Since humans are unable to produce any of the omega-3 or omega-6 PUFAs, they both constitute imperative nutritional ingredients. Long-standing concerns about long-chain omega-3 fatty acids’ impact on diabetes management have been supported by experimental investigations that found significant increases in fasting glucose following omega-3 fatty acid supplementation and foods rich in PUFA and omega-3 fatty acid. Cellular explanations to explain the connection between inflammation and IR include mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and oxidative stress. Modifications in the lipid composition of mitochondrial membranes and/or receptor-mediated signaling may be part of the mechanism behind the activation of mitochondrial fusion by fish oil/omega-3 PUFA. The exact molecular processes by which omega-3 PUFAs control mitochondrial activity to defend against IR are still unknown.

Thalassemias are a group of congenital hemoglobin (Hb) disorders distinguished by dwindling or total curtailment of production of one or more globin chains of hemoglobin tetramers, ensuing in unrestrained destruction of red blood cells (RBC) that causes severe anemia. The severity of the disease often remains immensely variable. Children with thalassemia suffer from the disease's consequences and treatment complications. The disease also causes a negative impact on family members, who suffer mentally, socially, financially, and even physically. In this review, we highlight the challenges experienced by the family and caregivers; for instance, repeated blood transfusion as the dominant origin of tissue casualty, morbidity, and fatal clinical outcomes. Treatment modalities regarding thalassemias were not successful until the inception of bone marrow transplantation and gene therapy.

Insulin resistance (IR) is stated as diminished insulin action regardless of hyperinsulinemia. The usual target organs for insulin activities are the liver, skeletal muscle, and adipose tissue. Hence, the vasculature and kidneys are nonconventional target organs as the impacts of insulin on these are comparatively separate from other conventional target organs. Vasodilation is achieved by raising endothelial nitric oxide (NO) generation by initiating the phosphoinositide 3-kinase (PI3K) pathway. In insulin-nonresponsive conditions, this process is defective, and there is increased production of endothelin-1 through the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway, which predominates the NO effects, causing vasoconstriction. Renal tubular cells and podocytes have insulin receptors, and their purposeful importance has been studied, which discloses critical acts of insulin signaling in podocyte survivability and tubular action. Diabetic nephropathy (DN) is a prevalent problem in individuals with hypertension, poor glycemic management, hereditary susceptibility, or glomerular hyperfiltration. DN could be a significant contributing factor to end-stage renal disease (ESRD) that results from chronic kidney disease (CKD). IR and diabetes mellitus (DM) are the constituents of syndrome X and are accompanied by CKD progression. IR performs a key part in syndrome X leading to CKD. However, it is indistinct whether IR individually participates in enhancing the threat to CKD advancement rather than CKD complexity. CKD is an extensive public health problem affecting millions of individuals worldwide. The tremendous spread of kidney disease intensifies people’s health impacts related to communicable and noncommunicable diseases. Chronic disease regulator policies do not include CKD at global, local, and/or general levels. Improved knowledge of the character of CKD-associated problems might aid in reforming diagnosis, prevention, and management.

Graft tolerance is a pathophysiological condition heavily reliant on the dynamic interaction of the innate and adaptive immune systems. Genetic polymorphism determines immune responses to tissue/organ transplantation, and intricate humoral and cell-mediated mechanisms control these responses. In transplantation, the clinician's goal is to achieve a delicate equilibrium between the allogeneic immune response, undesired effects of the immunosuppressive drugs, and the existing morbidities that are potentially life-threatening. Transplant immunopathology involves sensitization, effector, and apoptosis phases which recruit and engages immunological cells like natural killer cells, lymphocytes, neutrophils, and monocytes. Similarly, these cells are involved in the transfer of normal or genetically engineered T cells. Advances in tissue transplantation would involve a profound knowledge of the molecular mechanisms that underpin the respective immunopathology involved and the design of precision medicines that are safe and effective.