The anti-diabetic and oral hypoglycaemic agent metformin, first used clinically in 1958, is today the first choice or ‘gold standard' drug for the treatment of type 2 diabetes and polycystic ovary disease. Of particular importance for the treatment of diabetes, metformin affords protection against diabetes-induced vascular disease. In addition, retrospective analyses suggest that treatment with metformin provides therapeutic benefits to patients with several forms of cancer. Despite almost 60 years of clinical use, the precise cellular mode(s) of action of metformin remains controversial. A direct or indirect role of adenosine monophosphate (AMP)-activated protein kinase (AMPK), the fuel gauge of the cell, has been inferred in many studies, with evidence that activation of AMPK may result from a mild inhibitory effect of metformin on mitochondrial complex 1, which in turn would raise AMP and activate AMPK. Discrepancies, however, between the concentrations of metformin used in in vitro studies versus therapeutic levels suggest that caution should be applied before extending inferences derived from cell-based studies to therapeutic benefits seen in patients. Conceivably, the effects, or some of them, may be at least partially independent of AMPK and/or mitochondrial respiration and reflect a direct effect of either metformin or a minor and, as yet, unidentified putative metabolite of metformin on a target protein(s)/signalling cascade. In this review, we critically evaluate the data from studies that have investigated the pharmacokinetic properties and the cellular and clinical basis for the oral hypoglycaemic, insulin-sensitising and vascular protective effects of metformin.

Over the past three decades, the incidence and prevalence of neuroendocrine tumors have gradually increased. Due to the slow-growing nature of these tumors, most cases are diagnosed at advanced stages. Prognosis and survival are associated with location of primary lesion, biochemical functional status, differentiation, initial staging, and response to therapy. Octreotide, the first synthetic somatostatin analog, was initially used for the management of gastrointestinal symptoms associated with functional carcinoid tumors. Its commercial development over time led to long-acting repeatable octreotide acetate, a long-acting version that provided greater administration convenience. Recent research demonstrates that octreotide’s efficacy has evolved beyond symptomatic management to targeted therapy with antitumoral effects. This review examines the history and development of octreotide, provides a synopsis on the classification, grading, and staging of neuroendocrine tumors, and reviews the evidence of long-acting repeatable octreotide acetate as monotherapy and in combination with other treatment modalities in the management of non-pituitary neuroendocrine tumors with special attention to recent high-quality Phase III trials.

Since the 1930s when Kimmelstiel and Wilson first described the classic nodular glomerulosclerosis lesions in diabetic kidneys, nephropathy has been recognized as a major and common complication of diabetes. Nearly 40% of diabetics around the world have microalbuminuria, a marker of progression to chronic kidney disease (CKD). Diabetic kidney disease (DKD) is also considered a leading cause of CKD worldwide. Given the significant morbidity, mortality, and health-care burden, several clinical and scientific societies continue to seek a better understanding of this disease. Screening for microalbuminuria and controlling hyperglycemia remain the pillars for the prevention of diabetic nephropathy. However, evidence from multiple studies suggests that controlling DKD is more challenging. Some studies suggest that there is variability in the incidence of renal complications among patients despite comparable hyperglycemic control. Therefore, there has been great interest in studying the inherent, renal protective role of the different antihyperglycemic agents. This review will shed light on the pathophysiology, screening, and diagnosis of DKD. It will also discuss the treatment and prevention of diabetic nephropathy, with a specific focus on comparing the mechanisms, safety profiles, and efficacy of the different antihyperglycemic medications.

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