Toxicity of Metformin and Hypoglycemic Therapies

Akhter, Muhammad Saeed; Uppal, Priyasha

doi:10.1053/j.ackd.2019.08.004

Cited by 19 publications

(12 citation statements)

References 123 publications

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“…Another advantage is that increased satiety by slowing the emptying of the gastric system leads to weight loss and improves cardiorenal risk factors involving lipid levels and blood pressure in type 2 diabetic patients. Obesity, hypertension, and hyperglycemia contribute to the development of renal and heart diseases, so this medication can decrease the progression or onset of CKD [67][68][69][70]. The most common disadvantage is a gastrointestinal side effect (diarrhea or vomiting) leading to dehydration, which can affect renal function.…”

Section: Glp-1mentioning

confidence: 99%

Drug Therapies Affecting Renal Function: An Overview

Alhassani¹,

Bagadood²,

Balubaid³

et al. 2021

Cureus

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Undesirable side effects of medication are inevitable. Due to the role of the kidneys in clearance and filtration, the renal system faces a unique situation when it comes to the side effects of drugs. It has an important role for different classes of drugs to be excreted, and drugs are a key factor for this system to be at risk. Medications in articles were divided into classes using the standard set by the Saudi Pharmaceutical Journal. Many drug classes cause renal insults. The top six classes were pain killers, antibiotics, proton pump inhibitors, antidiabetics, antihyperlipidemics, and agents for erectile dysfunction. Renal insults caused by these agents could vary in severity. Some drugs could cause nephrotoxicity from one dose, while others may only need continuous monitoring. Different populations also operate under different rules, as some people need dose adjustments while others who are medically free of major illnesses do not. A variety of unfavorable outcomes for the kidney could take place, such as acute kidney injury, chronic kidney disease, and end-stage renal disease, and unfortunately, some of these issues could lead to the need for renal replacement therapies. The outcome of this review paper will help multidisciplinary physicians to understand the renal side effects of the most used drug classes in the Kingdom of Saudi Arabia, their destructive mechanisms, and most importantly, the clinical presentations of renal dysfunction in relation to each class. Emphasizing these adverse effects will prevent future unfavorable outcomes, especially in commonly used drugs that are frequently prescribed for different age groups. Moreover, some of these drugs are considered to be over-the-counter medications, which makes them a serious problem that needs to be handled cautiously.

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Section: Glp-1mentioning

confidence: 99%

Drug Therapies Affecting Renal Function: An Overview

Alhassani¹,

Bagadood²,

Balubaid³

et al. 2021

Cureus

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“…5 Because metformin is excreted by kidneys, caution is also advised in individuals with chronic kidney disease (CKD); the risk of adverse effects increases with CKD, including lactic acidosis and gastrointestinal manifestations. 7 Another possibility to improve blood glucose management is the use of strategies based on combined therapies.…”

Section: Introductionmentioning

confidence: 99%

<p>Lycopene Improves the Metformin Effects on Glycemic Control and Decreases Biomarkers of Glycoxidative Stress in Diabetic Rats</p>

Figueiredo¹,

Lima²,

Inácio³

et al. 2020

DMSO

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Introduction Oxidative stress and exacerbated generation of advanced glycation end products (AGEs) participate in the onset of diabetic complications. Lycopene is a potent antioxidant; evidence accounts for its ability to mitigate diabetic disturbances, including the deleterious events of advanced glycation. Therefore, this carotenoid has emerged as a candidate to be used in combination with antidiabetic drugs, such as metformin, attempting to counteract the glycoxidative stress. This study investigated the effects of the treatments with lycopene or metformin, alone or in combination, on glycoxidative stress biomarkers and antioxidant defenses in diabetic rats. Methods Streptozotocin-induced diabetic rats were treated for 35 days with lycopene (45 mg/kg) or metformin (250 mg/kg), alone or as mixtures in yoghurt. Plasma levels of glucose, triglycerides, cholesterol, thiobarbituric acid reactive substances and protein carbonyl groups (biomarkers of oxidative damage), fluorescent AGEs (biomarkers of advanced glycation), and paraoxonase 1 activity (antioxidant enzyme) were assessed. Changes in the hepatic and renal levels of glycoxidative damage biomarkers and the activities of antioxidant enzymes were investigated. Results The combination of lycopene with metformin maintained the beneficial effects of the isolated treatments, improving the glucose tolerance and lipid profile, lessening biomarkers of oxidative damage, and increasing the paraoxonase 1 activity. Besides, the combined therapy caused further decreases in postprandial glycemia, plasma levels of cholesterol and AGEs, avoided lipid peroxidation (plasma, kidney), and increased antioxidant defenses, mainly the activity of superoxide dismutase (liver, kidney), indicating the maintenance of the lycopene effects. Conclusion Lycopene combined with metformin may act synergistically in the control of postprandial glycemia, dyslipidemia and glycoxidative stress, as well as increased antioxidant defenses, arising as a promising therapeutic strategy to mitigate diabetic complications.

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“…S3G). A recent synthetic GYS1 inhibitor, yGsy2p-IN-1, robustly inhibited purified GYS1 and decreased 14 C-glucose incorporation in cell lysates 40 . We report here that yGsy2p-IN-1 successfully reduced glycogen levels and limited cell viability in ATC cells (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

“…16.480663 doi: bioRxiv preprint differentiated thyroid cancer in combination with RAI 8,12,13 . However, metformin has many metabolic targets, and the therapeutic efficacy in cancer patients remains controversial 14,15 .…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Glycogen Metabolism Induces Reactive Oxygen Species-Dependent Apoptosis in Anaplastic Thyroid Cancer

Davidson

Tomczak

Amiel

et al. 2022

Preprint

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Anaplastic thyroid cancer (ATC) is one of the most lethal solid tumors, yet there are no effective, long-lasting treatments for ATC patients. Most tumors, including tumors of the endocrine system, exhibit an increased consumption of glucose to fuel cancer progression, and some cancers meet this high glucose requirement by metabolizing glycogen. Our goal was to determine if ATC cells metabolize glycogen and if this could be exploited for treatment. We detected glycogen synthase and glycogen phosphorylase (PYG) isoforms in normal thyroid and thyroid cancer cell lines and patient-derived biopsy samples. Inhibition of PYG using CP-91,149 induced apoptosis in ATC cells but not normal thyroid cells. CP-91,149 decreased NADPH levels and induced reactive oxygen species accumulation. CP-91,149 severely blunted ATC tumor growth in vivo. Our work establishes glycogen metabolism as a novel metabolic process in thyroid cells that presents a unique, oncogenic target that could offer an improved clinical outcome.

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Toxicity of Metformin and Hypoglycemic Therapies

Cited by 19 publications

References 123 publications

Drug Therapies Affecting Renal Function: An Overview

Drug Therapies Affecting Renal Function: An Overview

<p>Lycopene Improves the Metformin Effects on Glycemic Control and Decreases Biomarkers of Glycoxidative Stress in Diabetic Rats</p>

Inhibition of Glycogen Metabolism Induces Reactive Oxygen Species-Dependent Apoptosis in Anaplastic Thyroid Cancer

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