Metformin and Its Implication in Cancer Therapy

Metformin has been used for almost half a century as the first line of treatment for type 2 diabetes. Mechanisms of action are still incompletely known, recent studies have shown that metformin exerts its effects through several mechanisms, including the stimulation of AMP-activated protein kinase, decreasing production of cyclic AMP, inhibition of mitochondrial complex I of the electron transport chain, targeting glycerophosphate dehydrogenase and altering gut microbiota. In recent years, studies have shown that patients with type 2 diabetes mellitus have a lower risk of developing cancer, and patients with cancer and type 2 diabetes have a lower mortality. Experimental studies have demonstrated that metformin has anti-tumor activity by inhibiting mTORC1 signaling pathway and mitochondrial complex, inhibiting tumor growth and proliferation, and inducing cellular apoptosis. There are multiple studies showing that combination of metformin with different types of anti-cancer therapies may reduce toxicities and tumor resistance. This chapter is focused on the progress made in understanding the anti-tumor effect of metformin and its association with cancer therapy

Metformin and Its Benefits in Improving Gut Microbiota Disturbances in Diabetes Patients

The human gastrointestinal tract presents a vastly population of microorganisms, called the microbiota. The presence of these microorganisms offers many benefits to the host, through a range of physiological functions. However, there is a potential for these mechanisms to be disrupted condition, known as dysbiosis. Recent results are showing important associations between diabetes and the gut microbiota and how the intestinal flora can influence the prognosis of this illness. Microbial intestinal imbalance has been linked to alterations in insulin sensitivity and in glucose metabolism and may play an important role in the development of diabetes. Metformin is one of the most important and widely used first-line medications for the management of type 2 diabetes (T2D). It is a complex drug with multiple sites of action and multiple molecular mechanisms. In recent years, attention has been directed to other modes of action, other than the classic ones, with increasing evidence of a major key role of the intestine. By analysing the effects of metformin on the homeostasis of the microbiota of diabetes patients, our present topic becomes one of the major importance in understanding how metformin therapy can improve gut microbiota dysbiosis and thus provide a better outcome for this illness

Atypical onset of diabetes in a teenage girl: a case report

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Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Diabesity: Were We are Wrong and What is the Cost?

Obesity, metabolic syndrome, prediabetes and dislipidemia are the major risk factors for developing type 2 diabetes and posible severe complications which can decrese quality of life and increase population mortality