Medical Management of Uncomplicated Obesity
Susan L. McElroy, David B. Allison, George A. Bray in Obesity and Mental Disorders, 2006
Metformin is a drug used in the treatment of type 2 diabetes that decreases hepatic gluconeogenesis and increases insulin sensitivity. Gokcel et al. (34) demonstrated that metformin achieved similar weight loss to orlistat over a six-month period. Kay et al. (35) studied the effects of metformin on obese, hyperinsulinemic, and nondiabetic subjects. When compared to placebo the metformin group achieved significantly greater weight loss (6.5 ± 0.8 vs. 3.8 ± 0.4%, p < 0.01) and improvement in their hyperinsulinemia. In patients with fasting hyperglycemia, metformin accounted for greater weight loss than placebo, but less than life-style changes alone. The average weight loss was 0.1, 2.1, and 5.6 kg in the placebo, metformin, and lifestyle-intervention groups, respectively (p < 0.001) (36).
Gastrointestinal Function and Toxicology in Minipigs
Shayne C. Gad in Toxicology of the Gastrointestinal Tract, 2018
It has been shown there are breed specific differences in pharmacokinetic profiles of intravenously and orally administered drugs. Recently, the pharmacokinetic profile of Metformin and verapamil was assessed in all four breeds of commonly used minipigs. Metformin is an orally administered drug for treatment of hyperglycemia in type II diabetes. Metformin does not undergo first-pass metabolism through the liver, but rather is rapidly renally cleared and excreted (Graham et al. 2011). Verapamil, a calcium channel blocker used to treat hypertension, undergoes extensive metabolism and forms several inactive metabolites, as well as the active metabolite nor-verapamil (Tracy et al. 1999, Bhatti and Foster 1997). Additionally, it is a chiral drug, with species specific differences in preferential metabolism of R-and S-verapamil and nor-verapamil (Patel et al. 2017).
Management of Obesity-Associated Type 2 Diabetes
Emmanuel C. Opara, Sam Dagogo-Jack in Nutrition and Diabetes, 2019
Metformin is presently the only biguanide available for use in the United States. Metformin acts primarily by reducing hepatic glucose output and increasing peripheral glucose uptake [145]. This agent is considered a first-line medication in the treatment of obese patients with type 2 diabetes, because it does not promote weight gain, and because it may facilitate weight loss. Additionally, it has the advantage of not causing hypoglycemia. The most feared complication of metformin use is the development of lactic acidosis. In patients who have conditions predisposing to hypoxia, such as congestive heart failure requiring medical therapy, cardiovascular collapse, acute myocardial infarction, renal insufficiency, and septicemia, the incidence of lactic acidosis is presumably higher. According to the product labeling, metformin is contraindicated in these patients. Caution should also be used in patients older than 80 years, those with hepatic disease, and those with chronic obstructive pulmonary disease associated with hypoxemia; metformin should also be stopped before and for 48 hours after contrast-media administration [146,147].
Protective effect of metformin against rotenone-induced parkinsonism in mice
Published in Toxicology Mechanisms and Methods, 2020
Dong-Xin Wang, An-Di Chen, Qing-Jun Wang, Yue-Yang Xin, Jie Yin, Yu-Hong Jing
Metformin is a traditional clinical drug for treating type 2 diabetes. In addition to the hypoglycemic effect, it can protect β-cell against lipotoxicity via the suppression of ER stress (Simon-Szabo et al. 2014), and prevent ER stress-induced apoptosis through AMPK-PI3K-c-Jun NH2 pathway (Jung et al. 2012). Its other effects, such as anticancer (Podhorecka et al. 2017) and anti-aging (Martin-Montalvo et al. 2013) effects, are attracting researchers’ attention in recent years. Moreover, it has been found that orally administered metformin rapidly crossed the blood–brain barrier and was distributed to various brain regions (Łabuzek et al. 2010), thus providing neuroprotective effects in the brain. The study conducted by Ge et al. showed that metformin could protect hippocampus from ischemic damage through PI3K/Akt1/JNK3/c-Jun signaling pathway (Ge et al. 2017). More recently, several studies have shown that metformin provides protection against MPTP induced neurotoxicity, which might be mediated by inhibition of α-synuclein phosphorylation and induction of neurotrophic factors as well as antioxidant activity (Patil et al. 2014; Katila et al. 2017).
Host-directed therapies for malaria and tuberculosis: common infection strategies and repurposed drugs
Published in Expert Review of Anti-infective Therapy, 2022
Piyush Baindara, Sonali Agrawal, O. L. Franco
Metformin is a common drug for treating diabetes mellitus type 2. In malaria, it is reported that metformin impairs the parasite liver stage of both rodent-infecting P. berghei and human-infecting P. falciparum parasites [197]. Moreover, when metformin was provided in combination with conventional antimalarial drugs, it not only reduced the total burden of P. berghei infection but also substantially lessened disease severity in mice [197]. However, the use of metformin in TB is also reported in several studies. In an in vitro study, metformin treatment is found to be associated with increased production of mitochondrial reactive oxygen species, which induced phagosome-lysosome fusion in infected macrophages, thus reducing Mtb survival [198]. Additionally, metformin treatment is associated with enhanced specific immune responses, reduced chronic inflammation, and lung pathology, and decreased disease severity in diabetic patients with TB [199]. These findings indicate that repurposing of metformin in a prophylactic regimen could be considered for malaria and TB.
Glibenclamide as a neuroprotective antidementia drug
Published in Archives of Physiology and Biochemistry, 2022
Alexander Zubov, Zamira Muruzheva, Maria Tikhomirova, Marina Karpenko
The basis of any treatment for T2DM is adherence to a hypoglycaemic diet and lifestyle changes in order to reduce body weight. It is also important to control the levels of blood lipids and arterial tension. If it is not possible to achieve the necessary results by changing the lifestyle, oral hypoglycaemic drugs – sulfonylureas (glibenclamide) and biguanides (metformin) are prescribed. Metformin reduces hepatic insulin resistance, leading to a decrease in glucose release by the liver. As this drug does not have a direct effect on pancreatic insulin secretion, it does not affect fasting plasma insulin. Sulfonylurea drugs, in contrast, stimulate insulin secretion. They cause closure of the potassium adenosine triphosphate-dependent (KATP) channels in the cytoplasmic membrane of pancreatic β-cells. Different drugs of the sulfonylurea class have different pharmacological effects, depending on the effect on the KATP channels.