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1.
Int Immunopharmacol ; 109: 108903, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1885844

ABSTRACT

With the widespread use of volatile anesthetic agents in the prolonged sedation for COVID-19 pneumonia and ARDS, there is an urgent need to investigate the effects and treatments of lengthy low-concentration inhaled anesthetics exposure on cognitive function in adults. Previous studies showed that general anesthetics dose- and exposure length-dependently induced neuroinflammatory response and cognitive decline in neonatal and aging animals. The anti-diabetes drug metformin has anti-neuroinflammation effects by modulating microglial polarization and inhibiting astrocyte activation. In this study, we demonstrated that the inhalation of 1.3% isoflurane (a sub-minimal alveolar concentration, sub-MAC) for 6 h impaired recognition of novel objects from Day 1 to Day3 in adult mice. Prolonged sub-MAC isoflurane exposure also triggered typically reactive microglia and A1-like astrocytes in the hippocampus of adult mice on Day 3 after anesthesia. In addition, prolonged isoflurane inhalation switched microglia into a proinflammatory M1 phenotype characterized by elevated CD68 and iNOS as well as decreased arginase-1 and IL-10. Metformin pretreatment before anesthesia enhanced cognitive performance in the novel object test. The positive cellular modifications promoted by metformin pretreatment included the inhibition of reactive microglia and A1-like astrocytes and the polarization of microglia into M2 phenotype in the hippocampus of adult mice. In conclusion, prolonged sub-MAC isoflurane exposure triggered significant hippocampal neuroinflammation and cognitive decline in adult mice which can be alleviated by metformin pretreatment via inhibiting reactive microglia and A1-like astrocytes and promoting microglia polarization toward anti-inflammatory phenotype in the hippocampus.


Subject(s)
Anesthetics , COVID-19 , Cognitive Dysfunction , Isoflurane , Metformin , Animals , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/drug therapy , Isoflurane/pharmacology , Isoflurane/therapeutic use , Metformin/pharmacology , Metformin/therapeutic use , Mice , Microglia
2.
Expert Opin Pharmacother ; 22(16): 2149-2165, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1868186

ABSTRACT

INTRODUCTION: An increasing number of older patients has type 2 diabetes treated with different oral antidiabetic agents whose safety may raise concern considering some particularities of a heterogeneous elderly population. AREAS COVERED: This article discusses some characteristics of older patients that could increase the risk of adverse events, with a focus on hypoglycemia. It describes the most frequent and/or severe complications reported in the elderly in both randomized controlled trials and observational studies with metformin, sulfonylureas, meglitinides, alpha-glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase-4 inhibitors (gliptins) and sodium-glucose cotransporter type 2 inhibitors (gliflozins). EXPERT OPINION: Old patients may present comorbidities (renal impairment, vascular disease, heart failure, risk of dehydration, osteoporosis, cognitive dysfunction) that could increase the risk of severe adverse events. Sulfonylureas (and meglitinides) induce hypoglycemia, which may be associated with falls/fractures and cardiovascular events. Medications lacking hypoglycemia should be preferred. Gliptins appear to have the best tolerance/safety profile whereas gliflozins exert a cardiorenal protection. However, data are lacking in very old or frailty old patients so that caution and appropriate supervision of such patients are required. Taking advantage of a large choice of pharmacotherapies, personalized treatment is recommended based upon both drug safety profiles and old patient individual characteristics.


Subject(s)
Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Metformin , Aged , Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Humans , Hypoglycemic Agents/adverse effects , Sulfonylurea Compounds/adverse effects
3.
Theranostics ; 12(6): 2722-2740, 2022.
Article in English | MEDLINE | ID: covidwho-1780236

ABSTRACT

Aging is a natural process, which plays a critical role in the pathogenesis of a variety of diseases, i.e., aging-related diseases, such as diabetes, osteoarthritis, Alzheimer disease, cardiovascular diseases, cancers, obesity and other metabolic abnormalities. Metformin, the most widely used antidiabetic drug, has been reported to delay aging and display protective effect on attenuating progression of various aging-related diseases by impacting key hallmark events of aging, including dysregulated nutrient sensing, loss of proteostasis, mitochondrial dysfunction, altered intercellular communication, telomere attrition, genomic instability, epigenetic alterations, stem cell exhaustion and cellular senescence. In this review, we provide updated information and knowledge on applications of metformin in prevention and treatment of aging and aging-related diseases. We focus our discussions on the roles and underlying mechanisms of metformin in modulating aging and treating aging-related diseases.


Subject(s)
Metformin , Aging/pathology , Cellular Senescence , Genomic Instability , Humans , Metformin/pharmacology , Metformin/therapeutic use , Telomere
4.
Sci Rep ; 12(1): 5553, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1768861

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a new pandemic the entire world is facing since December of 2019. Several risk factors are identified in developing severe disease and one of which is preexisting type 2 diabetes mellitus. Metformin is known to have host-directed anti-viral and anti-inflammatory properties. However, whether these effects offer lower mortality remains unclear. In this retrospective study, we aim to address whether metformin use prior to admission decreases mortality in patients with COVID-19 and pre-existing type 2 diabetes mellitus. A total of 1356 hospitalized patients with COVID-19 and pre-existing type 2 diabetes mellitus was analyzed by multivariable regression. Covariates that potentially confound the association were further adjusted using propensity score matching or inverse probability of treatment weighting. We found that metformin therapy prior to admission in patients with COVID-19 and type 2 diabetes mellitus was significantly associated with less primary outcome events including in-hospital mortality and hospice care enrollment with an odds ratio (OR) of 0.25 (95% CI 0.06-0.74) and less in-hospital length of stay, compared to the non-metformin group. Our results provide supporting evidence that metformin may confer increased survival in patients with COVID-19 and type 2 diabetes mellitus treated with metformin prior to hospitalization.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Metformin , COVID-19/drug therapy , Diabetes Mellitus, Type 2/chemically induced , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Humans , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Retrospective Studies
5.
Metabolism ; 131: 155196, 2022 06.
Article in English | MEDLINE | ID: covidwho-1768409

ABSTRACT

BACKGROUND: Diabetes is an independent predictor of poor outcomes in patients with COVID-19. We compared the effects of the preadmission use of antidiabetic medications on the in-hospital mortality of patients with COVID-19 having type 2 diabetes. METHODS: A systematic search of PubMed, EMBASE, Scopus and Web of Science databases was performed to include studies (except case reports and review articles) published until November 30, 2021. We excluded papers regarding in-hospital use of antidiabetic medications. We used a random-effects meta-analysis to calculate the pooled OR (95% CI) and performed a sensitivity analysis to confirm the robustness of the meta-analyses. MAIN FINDINGS: We included 61 studies (3,061,584 individuals), which were rated as having low risk of bias. The OR (95% CI) indicated some medications protective against COVID-related death, including metformin [0.54 (0.47-0.62), I2 86%], glucagon-like peptide-1 receptor agonist (GLP-1RA) [0.51 (0.37-0.69), I2 85%], and sodium-glucose transporter-2 inhibitor (SGLT-2i) [0.60 (0.40-0.88), I2 91%]. Dipeptidyl peptidase-4 inhibitor (DPP-4i) [1.23 (1.07-1.42), I2 82%] and insulin [1.70 (1.33-2.19), I2 97%] users were more likely to die during hospitalization. Sulfonylurea, thiazolidinedione, and alpha-glucosidase inhibitor were mortality neutral [0.92 (95% CI 0.83-1.01, I2 44%), 0.90 (95% CI 0.71-1.14, I2 46%), and 0.61 (95% CI 0.26-1.45, I2 77%), respectively]. The sensitivity analysis indicated that our findings were robust. CONCLUSIONS: Metformin, GLP-1RA, and SGLT-2i were associated with lower mortality rate in patients with COVID-19 having type 2 diabetes. DPP-4i and insulin were linked to increased mortality. Sulfonylurea, thiazolidinedione, and alpha-glucosidase inhibitors were mortality neutral. These findings can have a large impact on the clinicians' decisions amid the COVID-19 pandemic.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Insulins , Metformin , Sodium-Glucose Transporter 2 Inhibitors , Thiazolidinediones , COVID-19/drug therapy , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Glucagon-Like Peptide-1 Receptor/agonists , Humans , Hypoglycemic Agents/pharmacology , Insulins/therapeutic use , Metformin/therapeutic use , Pandemics , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sulfonylurea Compounds/therapeutic use , Thiazolidinediones/therapeutic use
6.
Medicina (Kaunas) ; 58(3)2022 Mar 16.
Article in English | MEDLINE | ID: covidwho-1742545

ABSTRACT

Metformin (MTF) occupies a major and fundamental position in the therapeutic management of type 2 diabetes mellitus (T2DM). Gender differences in some effects and actions of MTF have been reported. Women are usually prescribed lower MTF doses compared to men and report more gastrointestinal side effects. The incidence of cardiovascular events in women on MTF has been found to be lower to that of men on MTF. Despite some promising results with MTF regarding pregnancy rates in women with PCOS, the management of gestational diabetes, cancer prevention or adjunctive cancer treatment and COVID-19, most robust meta-analyses have yet to confirm such beneficial effects.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Metformin , Polycystic Ovary Syndrome , COVID-19/drug therapy , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Female , Humans , Hypoglycemic Agents/adverse effects , Male , Metformin/pharmacology , Metformin/therapeutic use , Pregnancy , Sex Factors
8.
Br J Clin Pharmacol ; 88(6): 2642-2656, 2022 06.
Article in English | MEDLINE | ID: covidwho-1672998

ABSTRACT

AIMS: The COVID-19 pandemic is a global public health emergency and patients with diabetes mellitus (DM) are disproportionately affected, exhibiting more severe outcomes. Recent studies have shown that metformin is associated with improved outcomes in patients with COVID-19 and DM and may be a potential candidate for drug repurposing. We aimed to investigate the effects of metformin on outcomes in patients with COVID-19 and DM. METHODS: Databases (PubMed, Scopus, Web of Science, EMBASE, Clinicaltrials.gov and Cochrane library) were searched up to 10 April 2021 for studies reporting data on metformin use in COVID-19 patients with DM. The risk of bias was assessed using the Newcastle-Ottawa scale. Certainty of evidence was rated using the GRADE approach. The primary outcome was mortality reported as odds ratio (OR). A random-effects meta-analysis was carried out on both unadjusted and adjusted ORs. This study is registered with PROSPERO, CRD42020221842. RESULTS: In total, 2 916 231 patients from 32 cohort studies were included in the quantitative and qualitative synthesis. The meta-analysis showed that metformin was significantly associated with lower mortality in COVID-19 patients with DM in both unadjusted (OR 0.61 [95% confidence interval: 0.53-0.71], P < .00001, I2  = 70%) and adjusted (OR 0.78 [95% confidence interval: 0.69-0.88], P < .00001, I2  = 67%) models. CONCLUSION: Poor outcomes in COVID-19 patients with DM can be attributed to inadequate glycaemic control and weakened immune responses. Metformin has multiple effects that can improve outcomes in patients with DM and our findings highlight a possible role of its use. However, robust randomised trials are needed to thoroughly assess its use.


Subject(s)
COVID-19 , Diabetes Mellitus , Metformin , Bias , COVID-19/drug therapy , Diabetes Mellitus/drug therapy , Diabetes Mellitus/epidemiology , Humans , Metformin/therapeutic use , Pandemics
9.
J Thromb Thrombolysis ; 53(2): 363-371, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1638608

ABSTRACT

Diabetes mellitus (DM) is associated with a greater risk of COVID-19 and an increased mortality when the disease is contracted. Metformin use in patients with DM is associated with less COVID-19-related mortality, but the underlying mechanism behind this association remains unclear. Our aim was to explore the effects of metformin on markers of inflammation, oxidative stress, and hypercoagulability, and on clinical outcomes. Patients with DM on metformin (n = 34) and metformin naïve (n = 41), and patients without DM (n = 73) were enrolled within 48 h of hospital admission for COVID-19. Patients on metformin compared to naïve patients had a lower white blood cell count (p = 0.02), d-dimer (p = 0.04), urinary 11-dehydro thromboxane B2 (p = 0.01) and urinary liver-type fatty acid binding protein (p = 0.03) levels and had lower sequential organ failure assessment score (p = 0.002), and intubation rate (p = 0.03), fewer hospitalized days (p = 0.13), lower in-hospital mortality (p = 0.12) and lower mortality plus nonfatal thrombotic event occurrences (p = 0.10). Patients on metformin had similar clinical outcomes compared to patients without DM. In a multiple regression analysis, metformin use was associated with less days in hospital and lower intubation rate. In conclusion, metformin treatment in COVID-19 patients with DM was associated with lower markers of inflammation, renal ischemia, and thrombosis, and fewer hospitalized days and intubation requirement. Further focused studies are required to support these findings.


Subject(s)
COVID-19 , Diabetes Mellitus , Hypoglycemic Agents , Metformin , Thrombosis , COVID-19/drug therapy , COVID-19/mortality , Diabetes Mellitus/drug therapy , Hospitalization , Humans , Hypoglycemic Agents/therapeutic use , Inflammation/complications , Inflammation/drug therapy , Metformin/therapeutic use , Oxidative Stress/drug effects , Retrospective Studies , Thrombosis/drug therapy
10.
Front Biosci (Schol Ed) ; 13(2): 202-207, 2021 12 03.
Article in English | MEDLINE | ID: covidwho-1559317

ABSTRACT

COVID-19, provoked by SARS-CoV-2, constitutes a global health issue with high rates of mortality. The presence of diabetes mellitus is associated with severe coronavirus COVID-19 as it is related to increased death rates in patients admitted to the intensive care unit. Acute kidney injury is a frequent complication among patients hospitalized for COVID-19 and is met with high morbidity and mortality. Here, we present a case of a diabetic patient with acute kidney injury, metformin-associated lactic acidosis, and COVID-19. Lactic acidosis is a relatively rare but noteworthy complication of metformin use. However, the combination of those life-threatening situations could prove fatal for the patients despite optimal medical care.


Subject(s)
Acidosis, Lactic , Acute Kidney Injury , COVID-19 , Diabetes Mellitus, Type 2 , Metformin , Acidosis, Lactic/chemically induced , Acute Kidney Injury/chemically induced , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Humans , Hypoglycemic Agents/adverse effects , Metformin/adverse effects , SARS-CoV-2
11.
Diabetes ; 70(12): 2745-2755, 2021 12.
Article in English | MEDLINE | ID: covidwho-1556100

ABSTRACT

Aging, obesity, and diabetes are major risk factors for the severe progression and outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019 [COVID-19]), but the underlying mechanism is not yet fully understood. In this study, we found that the SARS-CoV-2 spike protein physically interacts with cell surface GRP78, which promotes the binding to and accumulation in ACE2-expressing cells. GRP78 was highly expressed in adipose tissue and increased in humans and mice with older age, obesity, and diabetes. The overexpression of GRP78 was attributed to hyperinsulinemia in adipocytes, which was in part mediated by the stress-responsive transcription factor XBP-1s. Management of hyperinsulinemia by pharmacological approaches, including metformin, sodium-glucose cotransporter 2 inhibitor, or ß3-adrenergic receptor agonist, decreased GRP78 gene expression in adipose tissue. Environmental interventions, including exercise, calorie restriction, fasting, or cold exposure, reduced the gene expression of GRP78 in adipose tissue. This study provides scientific evidence for the role of GRP78 as a binding partner of the SARS-CoV-2 spike protein and ACE2, which might be related to the severe progression and outcome of COVID-19 in patients with older age, obesity, and diabetes. The management of hyperinsulinemia and the related GRP78 expression could be a therapeutic or preventative target.


Subject(s)
COVID-19/complications , COVID-19/pathology , Diabetes Mellitus , Obesity/complications , SARS-CoV-2 , Adipose Tissue/metabolism , Adrenergic beta-3 Receptor Agonists/pharmacology , Aged , Aging , Angiotensin-Converting Enzyme 2/metabolism , Animals , Cell Line , Humans , Hyperinsulinism/complications , Hyperinsulinism/drug therapy , Hypoglycemic Agents/pharmacology , Metformin/therapeutic use , Mice , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Spike Glycoprotein, Coronavirus/metabolism , Up-Regulation , Virus Internalization
12.
Front Immunol ; 12: 733921, 2021.
Article in English | MEDLINE | ID: covidwho-1551500

ABSTRACT

A hallmark of COVID-19 is a hyperinflammatory state associated with severity. Monocytes undergo metabolic reprogramming and produce inflammatory cytokines when stimulated with SARS-CoV-2. We hypothesized that binding by the viral spike protein mediates this effect, and that drugs which regulate immunometabolism could inhibit the inflammatory response. Monocytes stimulated with recombinant SARS-CoV-2 spike protein subunit 1 showed a dose-dependent increase in glycolytic metabolism associated with production of pro-inflammatory cytokines. This response was dependent on hypoxia-inducible factor-1α, as chetomin inhibited glycolysis and cytokine production. Inhibition of glycolytic metabolism by 2-deoxyglucose (2-DG) or glucose deprivation also inhibited the glycolytic response, and 2-DG strongly suppressed cytokine production. Glucose-deprived monocytes rescued cytokine production by upregulating oxidative phosphorylation, an effect which was not present in 2-DG-treated monocytes due to the known effect of 2-DG on suppressing mitochondrial metabolism. Finally, pre-treatment of monocytes with metformin strongly suppressed spike protein-mediated cytokine production and metabolic reprogramming. Likewise, metformin pre-treatment blocked cytokine induction by SARS-CoV-2 strain WA1/2020 in direct infection experiments. In summary, the SARS-CoV-2 spike protein induces a pro-inflammatory immunometabolic response in monocytes that can be suppressed by metformin, and metformin likewise suppresses inflammatory responses to live SARS-CoV-2. This has potential implications for the treatment of hyperinflammation during COVID-19.


Subject(s)
COVID-19/immunology , Metformin/pharmacology , Monocytes/drug effects , Monocytes/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Cells, Cultured , Humans
13.
Clin Endocrinol (Oxf) ; 96(4): 443-459, 2022 04.
Article in English | MEDLINE | ID: covidwho-1518007

ABSTRACT

CONTEXT: Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age. It is associated with dyslipidaemia and elevated plasma C-reactive protein (CRP), which increase the risks of cardiovascular disease (CVD). OBJECTIVE: To review the existing evidence on the effects of different pharmacological interventions on lipid profiles and CRP of women with PCOS. DATA SOURCES: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library, and Web of Science in April 2020 and updated the results in March 2021. STUDY SELECTION: The study included randomized controlled trials (RCTs) and follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). DATA EXTRACTION: Two independent researchers extracted data and assessed for risk of bias using the Cochrane risk of bias tool. Covidence systematic review software were used for blinded screening and study selection. DATA SYNTHESIS: In 29 RCTs, there were significant reductions in triglycerides with atorvastatin versus placebo [mean difference (MD): -0.21 mmol/L; 95% confidence interval (CI): -0.39, -0.03, I2 = 0%, moderate grade evidence]. Significant reductions were seen for low-density lipoprotein cholesterol (LDL-C) with metformin versus placebo [standardized mean difference (SMD): -0.41; 95% CI: -0.85, 0.02, I2 = 59%, low grade evidence]. Significant reductions were also seen for total cholesterol with saxagliptin versus metformin (MD: -0.15 mmol/L; 95% CI: -0.23, -0.08, I2 = 0%, very low grade evidence). Significant reductions in C-reactive protein (CRP) were seen for atorvastatin versus placebo (MD: -1.51 mmol/L; 95% CI: -3.26 to 0.24, I2 = 75%, very low-grade evidence). CONCLUSION: There were significant reductions in the lipid parameters when metformin, atorvastatin, saxagliptin, rosiglitazone and pioglitazone were compared with placebo or other agents. There was also a significant reduction of CRP with atorvastatin.


Subject(s)
Metformin , Polycystic Ovary Syndrome , Atorvastatin/therapeutic use , C-Reactive Protein , Cholesterol, LDL , Female , Humans , Metformin/therapeutic use
14.
Biomed Pharmacother ; 144: 112230, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1517059

ABSTRACT

The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 has become a serious challenge for medicine and science. Analysis of the molecular mechanisms associated with the clinical manifestations and severity of COVID-19 has identified several key points of immune dysregulation observed in SARS-CoV-2 infection. For diabetic patients, factors including higher binding affinity and virus penetration, decreased virus clearance and decreased T cell function, increased susceptibility to hyperinflammation, and cytokine storm may make these patients susceptible to a more severe course of COVID-19 disease. Metabolic changes induced by diabetes, especially hyperglycemia, can directly affect the immunometabolism of lymphocytes in part by affecting the activity of the mTOR protein kinase signaling pathway. High mTOR activity can enhance the progression of diabetes due to the activation of effector proinflammatory subpopulations of lymphocytes and, conversely, low activity promotes the differentiation of T-regulatory cells. Interestingly, metformin, an extensively used antidiabetic drug, inhibits mTOR by affecting the activity of AMPK. Therefore, activation of AMPK and/or inhibition of the mTOR-mediated signaling pathway may be an important new target for drug therapy in COVID-19 cases mostly by reducing the level of pro-inflammatory signaling and cytokine storm. These suggestions have been partially confirmed by several retrospective analyzes of patients with diabetes mellitus hospitalized for severe COVID-19.


Subject(s)
COVID-19/drug therapy , Diabetes Mellitus/drug therapy , Hypoglycemic Agents/therapeutic use , Immunity, Cellular/drug effects , Metformin/therapeutic use , Severity of Illness Index , COVID-19/epidemiology , COVID-19/immunology , COVID-19/metabolism , Diabetes Mellitus/epidemiology , Diabetes Mellitus/immunology , Diabetes Mellitus/metabolism , Humans , Hypoglycemic Agents/pharmacology , Immunity, Cellular/physiology , Lymphocytes/drug effects , Lymphocytes/immunology , Lymphocytes/metabolism , Metformin/pharmacology , Mortality/trends , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , TOR Serine-Threonine Kinases/antagonists & inhibitors , TOR Serine-Threonine Kinases/immunology , TOR Serine-Threonine Kinases/metabolism
15.
Expert Rev Endocrinol Metab ; 17(1): 1-19, 2022 01.
Article in English | MEDLINE | ID: covidwho-1500934

ABSTRACT

INTRODUCTION: While the main mode of transmission of coronavirus disease 2019 (COVID-19) is close contact with other individuals, the presence of chronic underlying diseases such as Diabetes Mellitus (DM) increases the chance of hospitalization and mortality rate due to infection. AREAS COVERED: To investigate the effects of COVID-19 infection in DM patients, we reviewed literature from Google Scholar search engine and PubMed database from '2013 to 2020' using the terms "COVID-19; SARS-CoV-2; Diabetes mellitus; obesity; Angiotensin-converting enzyme 2; ACE2; Insulin and Metformin. Evidence suggests that COVID-19 exacerbates the course of diabetes. Presence of pro-inflammatory conditions, increased expression of receptors, and more difficult control of glucose levels in diabetics COVID-19 patients are some of the problems that diabetic patients may face. Also, psychological problems caused by the COVID-19 epidemic in diabetic patients is one of the most important problems in these patients, which is less covered. EXPERT OPINION: DM is a strong and independent risk factor with a poor prognosis, which increases the risk of COVID-19 infection, the need for emergency services, the rate of hospitalization in the intensive care unit and also increases the mortality rate of COVID-19 patients.


Subject(s)
COVID-19 , Diabetes Mellitus , Metformin , Humans , Obesity/complications , SARS-CoV-2
16.
Geroscience ; 43(3): 1093-1112, 2021 06.
Article in English | MEDLINE | ID: covidwho-1499503

ABSTRACT

We are in the midst of the global pandemic. Though acute respiratory coronavirus (SARS-COV2) that leads to COVID-19 infects people of all ages, severe symptoms and mortality occur disproportionately in older adults. Geroscience interventions that target biological aging could decrease risk across multiple age-related diseases and improve outcomes in response to infectious disease. This offers hope for a new host-directed therapeutic approach that could (i) improve outcomes following exposure or shorten treatment regimens; (ii) reduce the chronic pathology associated with the infectious disease and subsequent comorbidity, frailty, and disability; and (iii) promote development of immunological memory that protects against relapse or improves response to vaccination. We review the possibility of this approach by examining available evidence in metformin: a generic drug with a proven safety record that will be used in a large-scale multicenter clinical trial. Though rigorous translational research and clinical trials are needed to test this empirically, metformin may improve host immune defenses and confer protection against long-term health consequences of infectious disease, age-related chronic diseases, and geriatric syndromes.


Subject(s)
COVID-19 , Communicable Diseases , Metformin , Aged , Communicable Diseases/drug therapy , Humans , Metformin/therapeutic use , Multicenter Studies as Topic , RNA, Viral , SARS-CoV-2
17.
Ir J Med Sci ; 191(2): 569-575, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1491362

ABSTRACT

BACKGROUND: The effect of preadmission metformin usage (PMU) on the mortality of coronavirus disease-2019 (COVID-19) patients with diabetes is conflicting. Most studies have focused on in-hospital mortality; however, mortality after discharge also increases in COVID-19 patients. AIMS: Examining the effect of PMU on all-cause mortality, including the post-discharge period. METHODS: Patients with diabetes who were hospitalised in 2020 due to COVID-19 were included in the study. They were divided into two groups: those with a history of metformin use (MF( +)) and those without such history (MF( -)). Propensity score matching (PSM) was performed at a ratio of 1:1 for age and sex. COX regression analyses were used to demonstrate risk factors for mortality. RESULTS: We investigated 4103 patients hospitalised for COVID-19. After excluding those without diabetes or with chronic liver/kidney disease, we included the remaining 586 patients, constituting 293 women (50%) with an overall mean age of 66 ± 11.9 years. After PSM analysis, the in-hospital and post-discharge mortality rates were higher in the MF( -) group though not significantly different. However, overall mortality was higher in the MF( -) group (51 (42.5%) vs. 35 (29.2%), p = 0.031). For overall mortality, the adjusted HR was 0.585 (95% CI: 0.371 - 0.920, p = 0.020) in the MF( +) group. CONCLUSION: PMU is associated with reducing all-cause mortality. This effect starts from the in-hospital period and becomes more significant with the post-discharge period. The main limitations were the inability to evaluate the compliance with metformin and the effects of other medications due to retrospective nature.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Metformin , Aftercare , Aged , COVID-19/drug therapy , Cohort Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Female , Humans , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Middle Aged , Patient Discharge , Retrospective Studies
18.
Drug Saf ; 43(7): 657-660, 2020 07.
Article in English | MEDLINE | ID: covidwho-1482335

ABSTRACT

INTRODUCTION: Hydroxychloroquine was recently promoted in patients infected with COVID-19 infection. A recent experimental study has suggested an increased toxicity of hydroxychloroquine in association with metformin in mice. OBJECTIVE: The present study was undertaken to investigate the reality of this putative drug-drug interaction between hydroxychloroquine and metformin using pharmacovigilance data. METHODS: Using VigiBase®, the WHO pharmacovigilance database, we performed a disproportionality analysis (case/non-case study). Cases were reports of fatal outcomes with the drugs of interest and non-cases were all other reports for these drugs registered between 1 January 2000 and 31 December 2019. Data with hydroxychloroquine (or metformin) alone were compared with the association hydroxychloroquine + metformin. Results are reported as ROR (reporting odds ratio) with their 95% confidence interval. RESULTS: Of the 10,771 Individual Case Safety Reports (ICSR) involving hydroxychloroquine, 52 were recorded as 'fatal outcomes'. In comparison with hydroxychloroquine alone, hydroxychloroquine + metformin was associated with an ROR value of 57.7 (23.9-139.3). In comparison with metformin alone, hydroxychloroquine + metformin was associated with an ROR value of 6.0 (2.6-13.8). CONCLUSION: Our study identified a signal for the association hydroxychloroquine + metformin that appears to be more at risk of fatal outcomes (particularly by completed suicides) than one of the two drugs when given alone.


Subject(s)
Coronavirus Infections , Drug Interactions , Drug Therapy, Combination , Hydroxychloroquine , Metformin , Pandemics , Pneumonia, Viral , Adult , Adverse Drug Reaction Reporting Systems/statistics & numerical data , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Drug Therapy, Combination/adverse effects , Drug Therapy, Combination/mortality , Female , Humans , Hydroxychloroquine/pharmacokinetics , Hydroxychloroquine/therapeutic use , Hypoglycemic Agents/pharmacokinetics , Hypoglycemic Agents/therapeutic use , Male , Metformin/pharmacokinetics , Metformin/therapeutic use , Middle Aged , Pharmacovigilance , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , SARS-CoV-2
19.
BMJ Open ; 11(10): e052310, 2021 10 20.
Article in English | MEDLINE | ID: covidwho-1476607

ABSTRACT

OBJECTIVES: To investigate the association between baseline use of glucose-lowering drugs and serious clinical outcome among patients with type 2 diabetes. DESIGN: Territory-wide retrospective cohort of confirmed cases of COVID-19 between January 2020 and February 2021. SETTING: All public health facilities in Hong Kong. PARTICIPANTS: 1220 patients with diabetes who were admitted for confirmed COVID-19. PRIMARY AND SECONDARY OUTCOME MEASURES: Composite clinical endpoint of intensive care unit admission, requirement of invasive mechanical ventilation and/or in-hospital death. RESULTS: In this cohort (median age 65.3 years, 54.3% men), 737 (60.4%) patients were treated with metformin, 385 (31.6%) with sulphonylureas, 199 (16.3%) with dipeptidyl peptidase-4 (DPP-4) inhibitors and 273 (22.4%) with insulin prior to admission. In multivariate Cox regression, use of metformin and DPP-4 inhibitors was associated with reduced incidence of the composite endpoint relative to non-use, with respective HRs of 0.51 (95% CI 0.34 to 0.77, p=0.001) and 0.46 (95% CI 0.29 to 0.71, p<0.001), adjusted for age, sex, diabetes duration, glycated haemoglobin (HbA1c), smoking, comorbidities and drugs. Use of sulphonylureas (HR 1.55, 95% CI 1.07 to 2.24, p=0.022) and insulin (HR 6.34, 95% CI 3.72 to 10.78, p<0.001) were both associated with increased hazards of the composite endpoint. CONCLUSIONS: Users of metformin and DPP-4 inhibitors had fewer adverse outcomes from COVID-19 compared with non-users, whereas insulin and sulphonylurea might predict a worse prognosis.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Metformin , Pharmaceutical Preparations , Aged , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Female , Glucose , Hong Kong/epidemiology , Hospital Mortality , Humans , Hypoglycemic Agents/therapeutic use , Male , Metformin/therapeutic use , Retrospective Studies , SARS-CoV-2
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