scholarly journals The Current and Potential Therapeutic Use of Metformin—The Good Old Drug

2021 ◽  
Vol 14 (2) ◽  
pp. 122
Author(s):  
Józef Drzewoski ◽  
Markolf Hanefeld
Keyword(s):  
Diabetes Mellitus ◽  
New Drugs ◽  
Favorable Effect ◽  
Oral Antidiabetic Agents ◽  
Beneficial Effects ◽  
Kidney Insufficiency ◽  
New Guidelines ◽  
Meta Analyses ◽  
Almost All ◽  
Risk Of Cancer

Metformin, one of the oldest oral antidiabetic agents and still recommended by almost all current guidelines as the first-line treatment for type 2 diabetes mellitus (T2DM), has become the medication with steadily increasing potential therapeutic indications. A broad spectrum of experimental and clinical studies showed that metformin has a pleiotropic activity and favorable effect in different pathological conditions, including prediabetes, type 1 diabetes mellitus (T1DM) and gestational diabetes mellitus (GDM). Moreover, there are numerous studies, meta-analyses and population studies indicating that metformin is safe and well tolerated and may be associated with cardioprotective and nephroprotective effect. Recently, it has also been reported in some studies, but not all, that metformin, besides improvement of glucose homeostasis, may possibly reduce the risk of cancer development, inhibit the incidence of neurodegenerative disease and prolong the lifespan. This paper presents some arguments supporting the initiation of metformin in patients with newly diagnosed T2DM, especially those without cardiovascular risk factors or without established cardiovascular disease or advanced kidney insufficiency at the time of new guidelines favoring new drugs with pleotropic effects complimentary to glucose control. Moreover, it focuses on the potential beneficial effects of metformin in patients with T2DM and coexisting chronic diseases.

Pharmacotherapy for Type 2 Diabetes Mellitus: What’s Up and Coming in the Glucagon-Like Peptide-1 (GLP-1) Pipeline?

2021 ◽  
pp. 089719002110490
Author(s):  
Mary J. Elder ◽  
Emily J. Ashjian
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glycemic Control ◽  
Glucagon Secretion ◽  
New Drugs ◽  
Beneficial Effects ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1), an incretin hormone, is known to lower glucose levels, suppress glucagon secretion, and slow gastric emptying. These properties make GLP-1 an ideal target in treating type 2 diabetes mellitus (T2DM). There are many FDA-approved GLP-1 agonists on the market today, several of which have demonstrated benefit beyond improving glycemic control. Given the beneficial effects of GLP-1 agonists in patients with T2DM, new drugs are in development that combine the mechanism of action of GLP-1 receptor agonism with novel mechanisms and with drugs that promote GLP-1 secretion. These agents are designed to improve glycemic control and target greater body weight reduction. This article discusses new GLP-1 drugs in the pipeline for the treatment of T2DM.

scholarly journals Cardiovascular safety of oral antidiabetic therapy in type 2 diabetes mellitus- review article

2017 ◽  
Vol 5 (5) ◽  
pp. 1742
Author(s):  
P. S. Singh ◽  
Sudhir K. Yadav ◽  
Himanshu Sharma ◽  
Manoj Kumar
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
New Drugs ◽  
Diabetic Patients ◽  
Cardiovascular Safety ◽  
Oral Antidiabetic Agents ◽  
Oral Antidiabetic ◽  
Increased Risk

Cardiovascular disease is the leading cause of morbidity and mortality among patients with type 2 diabetes mellitus (DM). There is twofold increased risk of cardiovascular (CV) mortality among diabetic patients as compared with nondiabetic patients. The glycemic efficacy of anti-diabetic drugs does not necessarily provide cardiovascular safety. Since 2008, US Food and Drug Administration has recommended that new drugs for type 2 DM should undergo clinical trials to demonstrate cardiovascular safety in addition to glycemic benefit. In 2012, European medicine agencies issued a similar recommendation. In this review, we have tried to examine the cardiovascular safety of oral antidiabetic agents in major published trials. Metformin remains the initial drug of choice in type2 DM till date. The sulfonylureas, one of oldest oral anti-diabetic drugs, have adverse cardiovascular events and are gradually being out classed by other second line drugs. The glitazones have been found to have adverse outcome in heart failure. The incretin based drugs have been found to have cardiovascular safety in various trials in recent past and their performances have been reassuring. There is lack of enough cardiovascular outcome data for meglitinides and glucosidase inhibitors. Various current trials have found sodium glucose cotransporter-2 inhibitors to have a potential for cardiovascular benefit. Careful selection of drug therapy with special attention for cardiovascular risk is important in selection and optimization of diabetic therapy.

scholarly journals Repurposing of Metformin as a Multifaceted and Multitasking Preventative and Treatment for Cancer

2021 ◽  
Author(s):  
Raymond Chang
Keyword(s):  
Diabetes Mellitus ◽  
Clinical Studies ◽  
Mechanisms Of Action ◽  
Cancer Development ◽  
Molecular Pathways ◽  
Preclinical Studies ◽  
Treatment Of Diabetes ◽  
Meta Analyses ◽  
Preclinical And Clinical Studies ◽  
Risk Of Cancer

Metformin is a cornerstone treatment of diabetes mellitus. Since 2005 when it has been first reported to reduce the risk of cancer in diabetics, a large number of preclinical and clinical studies have implicated its potential role as a preventative and adjunct therapy for a broad range of cancers. Whereas preclinical studies demonstrate its actions on a multitude of molecular pathways involving nearly all aspects of cancer development including metabolism, angiogenesis, apoptosis, autophagy, immunity, epigenetics, inflammation and crosstalk with the microbiome, other studies demonstrate its synergism with a range of anticancer modalities including chemotherapy, radiotherapy, immunotherapy, and targeted therapies. Furthermore, an increasing number of clinical studies not only confirm its preventative properties against cancers but have extended its potential for a possible adjunctive role in the neoadjuvant, adjuvant, maintenance and salvage therapies of cancer. This article intends to summarize the basic science that allows us to understand the complex multiple mechanisms of action of this remarkable multitasking molecule as well as review the recent meta-analyses that have summarized the clinical studies assessing the therapeutic efficacy of metformin for various cancers.

scholarly journals Antidiabetic drugs and the risk of cancer: beneficial, neutral, or detrimental?

2021 ◽  
Vol 12 (1) ◽  
pp. 74-81
Author(s):  
Taoreed Adegoke Azeez ◽  
Sharif Adeniyi Folorunso ◽  
Chinedu Eguzozie ◽  
Adeleke Adedapo Adegboyega
Keyword(s):  
Diabetes Mellitus ◽  
Clinical Trials ◽  
Epidemiological Studies ◽  
The Body ◽  
Antidiabetic Drugs ◽  
Pharmacological Agents ◽  
Middle Income ◽  
Beneficial Effects ◽  
Risk Of Cancer

Abstract The prevalence of diabetes mellitus is rapidly rising, especially in low- and middle-income countries. Also, early-onset diabetes is on the rise, and millions of individuals have to be on antidiabetic medications for a prolonged period. Therefore, more people are getting exposed to the adverse effects of antidiabetic medications. Cancer is among the top ranking causes of death worldwide. Researches are still ongoing to understand the etiologies, precipitants, risk factors, correlates, and predictors of cancers. Diabetes mellitus is associated with various cancers, as extensively documented in the literature. There are conflicting reports about the association between antidiabetic drugs and cancer. This is even of crucial importance, considering that the prevalence of diabetes is rising. Insulin glargine is reported to be associated with cancers, but clinical trials have not confirmed this. Metformin is largely believed to be beneficial in oncologic practice. Glibenclamide is reported to reduce tumor growth. The association between pioglitazone and bladder cancer is still an area for further research. Meglitinides have also been associated with cancers. Incretin-based therapy and the α-glucosidase inhibitors appear to have beneficial effects on cancers. There is still a need for randomized multicentric clinical trials to further substantiate and clarify reports from epidemiological studies. Further in vitro studies will also be necessary to characterize the interaction of these pharmacological agents with other molecules in the body.

Therapeutic Approaches to Alzheimer’s Type of Dementia: A Focus on FGF21 Mediated Neuroprotection

2019 ◽  
Vol 25 (23) ◽  
pp. 2555-2568 ◽  
Author(s):  
Rajeev Taliyan ◽  
Sarathlal K. Chandran ◽  
Violina Kakoty
Keyword(s):  
Diabetes Mellitus ◽  
Protein Trafficking ◽  
Metabolic Stress ◽  
Insulin Receptors ◽  
Metabolic Dysfunction ◽  
Beneficial Effects ◽  
Glucose And Lipid Metabolism ◽  
Endocrine Hormone ◽  
Metabolic Conditions ◽  
The Brain

Neurodegenerative disorders are the most devastating disorder of the nervous system. The pathological basis of neurodegeneration is linked with dysfunctional protein trafficking, mitochondrial stress, environmental factors and aging. With the identification of insulin and insulin receptors in some parts of the brain, it has become evident that certain metabolic conditions associated with insulin dysfunction like Type 2 diabetes mellitus (T2DM), dyslipidemia, obesity etc., are also known to contribute to neurodegeneration mainly Alzheimer’s Disease (AD). Recently, a member of the fibroblast growth factor (FGF) superfamily, FGF21 has proved tremendous efficacy in diseases like diabetes mellitus, obesity and insulin resistance (IR). Increased levels of FGF21 have been reported to exert multiple beneficial effects in metabolic syndrome. FGF21 receptors are present in certain areas of the brain involved in learning and memory. However, despite extensive research, its function as a neuroprotectant in AD remains elusive. FGF21 is a circulating endocrine hormone which is mainly secreted by the liver primarily in fasting conditions. FGF21 exerts its effects after binding to FGFR1 and co-receptor, β-klotho (KLB). It is involved in regulating energy via glucose and lipid metabolism. It is believed that aberrant FGF21 signalling might account for various anomalies like neurodegeneration, cancer, metabolic dysfunction etc. Hence, this review will majorly focus on FGF21 role as a neuroprotectant and potential metabolic regulator. Moreover, we will also review its potential as an emerging candidate for combating metabolic stress induced neurodegenerative abnormalities.

scholarly journals Early Renoprotective Effect of Ruxolitinib in a Rat Model of Diabetic Nephropathy

2021 ◽  
Vol 14 (7) ◽  
pp. 608
Author(s):  
Mohamed M. El-Kady ◽  
Reham A. Naggar ◽  
Maha Guimei ◽  
Iman M. Talaat ◽  
Olfat G. Shaker ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Kidney Disease ◽  
Rat Model ◽  
Diabetic Kidney Disease ◽  
Tubulointerstitial Fibrosis ◽  
Favorable Effect ◽  
Glomerular Sclerosis ◽  
Diabetic Kidney ◽  
Renoprotective Effect ◽  
Tgf Β1

Diabetic kidney disease (DKD) is still one of the unresolved major complications of diabetes mellitus, which leads ultimately to end-stage renal disease in both type 1 and type 2 diabetes patients. Available drugs that suppress the renin–angiotensin system have partially minimized the disease impact. Yet, there is an unmet need for new therapeutic interventions to protect the kidneys of diabetic patients. In DN, glomerular sclerosis and tubulointerstitial fibrosis are mediated through several pathways, of which JAK/STAT is a key one. The current study explored the potential renoprotective effect of the JAK1/JAK2 inhibitor ruxolitinib (at doses of 0.44, 2.2, and 4.4 mg·kg−1) compared to that of enalapril at a dose of 10 mg·kg−1, in a rat model of streptozotocin-induced diabetes mellitus over 8 weeks. The effect of ruxolitinib was assessed by determining urinary albumin/creatinine ratio, serum level of cystatin, and levels of TGF-β1, NF-κB, and TNF-α in renal tissue homogenates by biochemical assays, the glomerular sclerosis and tubulointerstitial fibrosis scores by histological analysis, and fibronectin, TGF-β1, and Vimentin levels by immunohistochemical staining with the respective antibodies. Our results revealed a significant early favorable effect of a two-week ruxolitinib treatment on the renal function, supported by a decline in the proinflammatory biomarkers of DKD. This pre-clinical study suggests that the renoprotective effect of ruxolitinib in the long term should be investigated in animals, as this drug may prove to be a potential option for the treatment of diabetic kidney disease.

scholarly journals Scanxiety: a scoping review about scan-associated anxiety

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e043215
Author(s):  
Kim Tam Bui ◽  
Roger Liang ◽  
Belinda E Kiely ◽  
Chris Brown ◽  
Haryana M Dhillon ◽  
...  
Keyword(s):  
Scoping Review ◽  
Perceived Risk ◽  
Data Extraction ◽  
Depression Scale ◽  
Cochrane Central Register ◽  
Contributing Factors ◽  
Positron Emission ◽  
Severity Scores ◽  
Almost All ◽  
Risk Of Cancer

ObjectivesTo identify available literature on prevalence, severity and contributing factors of scan-associated anxiety (‘scanxiety’) and interventions to reduce it.DesignSystematic scoping review.Data sourcesOvid MEDLINE, Ovid EMBASE, Ovid PsycINFO, Ovid Cochrane Central Register of Controlled Trials, Scopus, EBSCO CINAHL and PubMed up to July 2020.Study selectionEligible studies recruited people having cancer-related non-invasive scans (including screening) and contained a quantitative assessment of scanxiety.Data extractionDemographics and scanxiety outcomes were recorded, and data were summarised by descriptive statistics.ResultsOf 26 693 citations, 57 studies were included across a range of scan types (mammogram: 26/57, 46%; positron-emission tomography: 14/57, 25%; CT: 14/57, 25%) and designs (observation: 47/57, 82%; intervention: 10/57, 18%). Eighty-one measurement tools were used to quantify prevalence and/or severity of scanxiety, including purpose-designed Likert scales (17/81, 21%); the State Trait Anxiety Inventory (14/81, 17%) and the Hospital Anxiety and Depression Scale (9/81, 11%). Scanxiety prevalence ranged from 0% to 64% (above prespecified thresholds) or from 13% to 83% (‘any’ anxiety, if no threshold). Mean severity scores appeared low in almost all measures that quantitatively measured scanxiety (54/62, 87%), regardless of whether anxiety thresholds were prespecified. Moderate to severe scanxiety occurred in 4%–28% of people in studies using descriptive measures. Nine of 20 studies assessing scanxiety prescan and postscan reported significant postscan reduction in scanxiety. Lower education, smoking, higher levels of pain, higher perceived risk of cancer and diagnostic scans (vs screening scans) consistently correlated with higher scanxiety severity but not age, gender, ethnicity or marital status. Interventions included relaxation, distraction, education and psychological support. Six of 10 interventions showed a reduction in scanxiety.ConclusionsPrevalence and severity of scanxiety varied widely likely due to heterogeneous methods of measurement. A uniform approach to evaluating scanxiety will improve understanding of the phenomenon and help guide interventions.

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