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Diabetes Mellitus, Obesity, Lipoprotein Disorders and other Metabolic Diseases
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
There are multiple oral therapies for treating type 2 diabetes (Table 11.8). Metformin is the first-line drug for type 2 diabetes and lowers mortality in overweight diabetic patients. Many patients with type 2 DM require more than one oral hypoglycaemic drug to achieve good glucose control. Current US/European guidelines recommend assessing cardiovascular and renal disease when choosing a second-line oral hypoglycaemic drug.
Selected topics
Published in Henry J. Woodford, Essential Geriatrics, 2022
Metformin reduces hepatic gluconeogenesis, increases peripheral glucose uptake and increases insulin sensitivity. Typically, HbA1C values fall by 11–22 mmol/mol (1–2%).103 It has a low hypoglycaemia risk (severe hypoglycaemia around 0.6% per year v 5% per year with sulphonylureas).104 It may be associated with reduced appetite and weight loss, making it a particularly useful therapy for people who are overweight. Blood sugar monitoring may be unnecessary with metformin monotherapy. Lactic acidosis is a rare but reported serious complication of metformin therapy. However, a Cochrane review was unable to confirm this association.105 It is usually not recommended for people with marked cardiac or renal impairment (caution with eGFR below 45 mL/min/1.73m2, avoid if below 30). Treatment with metformin is associated with a lower risk of cardiovascular mortality compared to other oral hypoglycaemic agents or placebo (OR 0.74; 95% CI 0.62–0.89).106 For this reason, it is considered a first-line therapy. It also has a low cost. There is a risk of B12 deficiency while taking metformin.
Nuclear Factor Kappa-B: Bridging Inflammation and Cancer
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Mohammad Aslam Khan, Girijesh Kumar Patel, Haseeb Zubair, Nikhil Tyagi, Shafquat Azim, Seema Singh, Aamir Ahmad, Ajay Pratap Singh
Chemoprevention is described as the use of pharmacological agents to suppress the growth of cancer, and reverse the process of tumorigenesis in its earliest stages. Genetic mutations and epigenetic alterations play crucial role in the development of malignancies. Therefore, chemoprevention can only be achieved by understanding the underlying molecular mechanisms of carcinogenesis and the mechanism(s) of action of these agents [108]. Broadly, cancer chemopreventive agents can be grouped into four categories such as diet associated agents, hormonal, medications, and vaccines [109]. Phytochemicals derived from our dietary products control the growth of tumor cells both in vitro and in vivo by exhibiting various modes of action. They may act as antioxidants, pro-oxidants, and anti-inflammatory or antagonize tumor’s metabolism [109]. Moreover, chemopreventive agents derived from hormones are more effective against steroid-related cancers like breast and prostate cancer. Anti-inflammatory drugs, like aspirin, also act as chemopreventive agents in gastrointestinal cancer [110, 111]. Another prescribed drug for type II diabetes, metformin, was found to be associated with reduced risk of various cancers [112-114]. Chemopreventive property of cholesterol reducing drugs, statins, is evident in their inhibition of cancer growth, induction of apoptosis and inhibition of angiogenesis [114–116]. Virus or bacterial infection-associated cancers such as hepatocellular carcinoma, cervical cancer and stomach cancer can be inhibited by using vaccines [117, 118].
Recent developments in adjunct therapies for type 1 diabetes
Published in Expert Opinion on Investigational Drugs, 2022
Joseph G. Timmons, Lucy Littlejohn, James G. Boyle, John R. Petrie
The REMOVAL trial was a placebo-controlled, double-blind, multi-site international trial of metformin vs placebo for 36 months in 428 adults with T1D (over the age of 40 years) with three or more pre-specified cardiovascular risk factors. Baseline mean HbA1c was 8.1% (65 mmol/mol) [SD 0.9] for metformin and 8.0% (64 mmol/mol) [0.8] for placebo. It remains the largest and longest duration trial of metformin as adjunct therapy and the only one to incorporate a cardiovascular outcome of any type. The primary outcome was progression of mean far wall carotid intima media thickness (cIMT) as a surrogate for atherosclerosis progression, with maximal far wall cIMT (which does not exclude plaque) also pre-specified as a tertiary outcome. Of note, while the main results demonstrated no difference between active and placebo medication for the primary cIMT outcome, the tertiary maximal far wall cIMT outcome was reduced by metformin. This provides some proof of concept for a beneficial cardiovascular effect of metformin in T1D; interestingly the primary cIMT outcome was also reduced in nonsmokers as a subgroup [40]. Other benefits associated with metformin included weight loss of 1.17 kg (p < 0.0001), reduction in LDL cholesterol (−0.13 mmol/L p = 0.012) (secondary outcomes) and a reduction in insulin dose requirement by 2 units per day (p = 0.045; post hoc analysis) [41].
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.
Efficacy and safety of metformin in pregnant women with polycystic ovary syndrome: a systematic review with meta-analysis of randomized and non-randomized controlled trials
Published in Gynecological Endocrinology, 2022
Polycystic ovarian syndrome (PCOS) is related to infertility [1] and affects up to 15% of women of reproductive age [2,3]. This condition is also associated with obesity, insulin resistance, and difficulty in conceiving naturally [4]. When women with PCOS become pregnant, they will face pregnancy complications, such as miscarriage, preterm delivery, gestational diabetes, and pre-eclampsia [5–9]. Metformin has beneficial effects on several risk factors of hyperinsulinemia, insulin resistance, hyperandrogenemia, and obesity [10]. It is prescribed for the therapeutic management of PCOS for its potential benefits [11]. However, the use of metformin in pregnant women with PCOS remains controversial because metformin is classified by the U.S. Food and Drug Administration under pregnancy category B. Several studies have suggested that metformin use during pregnancy decreases the high incidence of miscarriage, preterm delivery, gestational diabetes, and pre-eclampsia associated with PCOS [10,12]. Metformin may improve fertility by reducing pregnancy complications by acting on oocytes [13] and the endometrium [14].