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1.
BMJ Open Diabetes Res Care ; 10(2)2022 Apr.
Article in English | MEDLINE | ID: covidwho-1779347

ABSTRACT

INTRODUCTION: This post hoc pooled analysis of four real-world studies (SURE Canada, Denmark/Sweden, Switzerland and UK) aimed to characterize the use of once-weekly (OW) semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), in patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: The Semaglutide Real-world Evidence (SURE) studies had a duration of ~30 weeks. Changes in glycated hemoglobin (HbA1c) and body weight (BW) were analyzed for the overall population and the following baseline subgroups: GLP-1RA-naïve/GLP-1RA switchers; body mass index <25/≥25-<30/≥30-<35/≥35 kg/m2; age <65/≥65 years; HbA1c <7%/≥7-≤8%/>8-≤9%/>9%; T2D duration <5/≥5-<10/≥10 years. Data for patients achieving treatment targets were analyzed in the overall population and the baseline HbA1c ≥7% subgroup. RESULTS: Of 1212 patients, 960 were GLP-1RA-naïve and 252 had switched to semaglutide from another GLP-1RA. In the overall population, HbA1c was reduced from baseline to end of study (EOS) by -1.1% point and BW by -4.7 kg; changes were significant for all subgroups. There were significantly larger reductions of HbA1c and BW in GLP-1RA-naïve versus GLP-1RA switchers and larger reductions in HbA1c for patients with higher versus lower baseline HbA1c. At EOS, 52.6% of patients in the overall population achieved HbA1c <7%. No new safety concerns were identified in any of the completed SURE studies. CONCLUSIONS: In this pooled analysis, patients with T2D initiating OW semaglutide showed significant improvements from baseline to EOS in HbA1c and BW across various baseline subgroups, including patients previously treated with a GLP-1RA other than semaglutide, supporting OW semaglutide use in clinical practice. TRAIL REGISTRATION NUMBERS: NCT03457012; NCT03631186; NCT03648281; NCT03876015.


Subject(s)
Diabetes Mellitus, Type 2 , Aged , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Glucagon-Like Peptides/therapeutic use , Glycated Hemoglobin A/analysis , Humans , Hypoglycemic Agents/therapeutic use
2.
Sci Rep ; 12(1): 5553, 2022 Apr 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
4.
BMC Pediatr ; 22(1): 48, 2022 01 19.
Article in English | MEDLINE | ID: covidwho-1633014

ABSTRACT

BACKGROUND: Between March 18th and May 13th 2020, the COVID-19 pandemic outbreak in Finland resulted in the closure of schools and the limitation of daycare (i.e. lockdown). Social distancing changed the daily routines of children with type 1 diabetes (T1D). Healthcare professionals were forced to adapt to the pandemic by replacing physical outpatient visits with virtual visits. However, the influence of the lockdown on glycemic control in these patients remained unknown. METHODS: In this retrospective register study from a pediatric diabetes outpatient clinic, we analyzed the glycemic data of T1D patients (n = 245; aged 4 to 16 years) before and under the lockdown. All the participants used continuous glucose monitoring (rtCGM or iCGM), two-thirds were on insulin pumps (CSII), and one-third on multiple daily insulin injections (MDI) therapy. RESULTS: In our patient cohort, time in range (TIR, n = 209) and mean glucose levels (n = 214) were similar prior to and under the lockdown (mean change 0.44% [95%CI: -1.1-2.0], p = 0.56 and -0.13 mmol/mol [95%CI: -0.3-0.1], p = 0.17, respectively). However, children treated with CSII improved their glycemic control significantly during the lockdown: TIR improved on average 2.4% [0.6-4.2] (p = 0.010) and mean blood glucose level decreased -0.3 mmol/mol [-0.6-(-0.1)] (p = 0.008). The difference was more pronounced in girls, adolescents and patients using conventional insulin pumps. CONCLUSIONS: The glycemic control in T1D children did not deteriorate under the lockdown, and patients on CSII even improved their control, which suggests that social distancing might have allowed families to use the insulin pump more accurately as out-of-home activities were on hold.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 1 , Adolescent , Blood Glucose , Blood Glucose Self-Monitoring , Child , Communicable Disease Control , Diabetes Mellitus, Type 1/drug therapy , Female , Glycemic Control , Humans , Hypoglycemic Agents/therapeutic use , Pandemics , Retrospective Studies , SARS-CoV-2
5.
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
6.
Curr Med Res Opin ; 38(3): 357-364, 2022 03.
Article in English | MEDLINE | ID: covidwho-1612282

ABSTRACT

Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are antidiabetic drugs with numerous pleiotropic and positive clinical effects, particularly regarding a reno-cardiovascular protective effect. More recent studies, including from our laboratory, have highlighted some novel anti-inflammatory activity of SGLT-2 inhibitors. This may confer a theoretical advantage in mitigating excessive cytokine production and inflammatory response associated with serious COVID-19 infection. Specifically, earlier research has demonstrated that SGLT-2 inhibitors are associated with a notable decrease in inflammatory indicators, for example, C-reactive protein, ferritin, and interleukin-6. Furthermore, SGLT-2 inhibitors exhibit a favourable impact on the vascular endothelium function; this could pertinence the prophylaxis of the thrombotic issues that arise in SARS-CoV-2. This review provides an overview of the COVID-19 indirect immune response mechanisms impacting the cardiovascular system and the possible effect of SGLT-2 inhibitors on the management of COVID-19.


Subject(s)
COVID-19 , Inflammation , Sodium-Glucose Transporter 2 Inhibitors , COVID-19/drug therapy , Glucose , Humans , Hypoglycemic Agents/therapeutic use , Inflammation/drug therapy , Inflammation/virology , SARS-CoV-2 , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
8.
Arch Pediatr ; 29(1): 27-29, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1561682

ABSTRACT

AIM: The COVID-19 pandemic has forced governments to impose lockdown policies, thus impacting patients with chronic diseases, such as type 1 diabetes. The aim of this study was to evaluate the impact of lockdown on glycemic control in type 1 diabetes patients. PATIENTS AND METHODS: We retrospectively evaluated patients using a continuous subcutaneous insulin infusion device during the nationwide lockdown. Children and adolescents aged 2-18 years followed up at the Pediatric Endocrinology Unit of Hospitalar São João in Portugal were included in the study. We collected data on the age, weight, insulin doses, and glycemic control of the patients before and after the restrictions. RESULTS: The study included 100 patients, 59 males, with a mean age of 12.5 years. Baseline data showed a suboptimal glycemic control with a median HbA1c of 7.9%. The lockdown was associated with an increase in the body mass index (BMI) of all patients (p = 0.009), particularly girls and older teenagers. Metabolic control deteriorated in the 10-13 age group (p = 0.03), with a 0.4% increase in HbA1c. CONCLUSION: To date, this is the largest study on the impact of lockdown on type 1 diabetes in patients using an insulin pump. The results highlight the importance of physical activity, parental supervision, and continuation of healthcare assistance through telemedicine in young individuals with type 1 diabetes.


Subject(s)
COVID-19/prevention & control , Diabetes Mellitus, Type 1/drug therapy , Glycemic Control/methods , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Pandemics/prevention & control , Quarantine , Adolescent , Blood Glucose , COVID-19/epidemiology , Child , Communicable Disease Control/methods , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/epidemiology , Female , Glycated Hemoglobin A/analysis , Glycated Hemoglobin A/metabolism , Humans , Hypoglycemic Agents/therapeutic use , Infusions, Subcutaneous , Insulin Infusion Systems/adverse effects , Male , Portugal/epidemiology , Retrospective Studies , SARS-CoV-2
11.
Am J Physiol Endocrinol Metab ; 322(1): E44-E53, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1518165

ABSTRACT

In December 2019, a pandemic emerged due to a new coronavirus that imposed various uncertainties and discoveries. It has been reported that diabetes is a risk factor for worst outcomes of COVID-19 and also that SARS-CoV-2 infection was correlated with the occurrence of diabetic ketoacidosis (DKA) in patients. The aim of this work is to discuss this correlation emphasizing the main case reports from 2020 while exploring the management of DKA during the course of COVID-19. Web of Science, PubMed, and Scopus databases were searched using two sets of Medical Subject Heading (MeSH) search terms or Title/Abstract words: Coronavirus Infections (Coronavirus Infections, Middle East Respiratory Syndrome, COVID-19) and Diabetic Ketoacidosis (Diabetic Ketoacidosis, Diabetic Acidosis, Diabetic Ketosis). There is a clear correlation between COVID-19 and DKA. The SARS-Cov-2 infection may precipitate both a hyperglycemic state and ketoacidosis occurrence in patients with diabetes and nondiabetic patients, which may lead to fatal outcomes. DKA in patients with COVID-19 may increase risk and worse outcomes. Hence, the SARS-Cov-2 infection presents a new perspective toward the management of glycemia and acidosis in patients with diabetes and nondiabetic patients, highlighting the need for rapid interventions to minimize the complications from COVID-19 while reducing its spreading.


Subject(s)
COVID-19/complications , Diabetic Ketoacidosis/complications , Blood Glucose/analysis , Blood Glucose Self-Monitoring , COVID-19/metabolism , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Diabetic Ketoacidosis/drug therapy , Diabetic Ketoacidosis/metabolism , Humans , Hyperglycemia/complications , Hyperglycemia/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin/administration & dosage , Insulin/therapeutic use , Prognosis , Risk Factors , Telemedicine
12.
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
13.
J Endocrinol Invest ; 45(4): 763-772, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1516940

ABSTRACT

INTRODUCTION: Several studies have shown that COVID-19 pandemic has a negative impact on type 2 diabetic mellitus (T2DM) patients' quality of life (QoL). However, very few studies were performed in Middle Eastern countries. AIM: The aim of the current study was to assess, the QoL and diabetes-specific QoL, treatment satisfaction and psychological distress of Lebanese patients with T2DMs using: the Audit of Diabetes-Dependent Quality of Life (ADDQoL), Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) and Kessler 10 (K10) questionnaires and to compare results to those obtained during the pre-COVID-19 period. RESULTS: 461 patients with T2DM participated in the study; 52.6% men, 47.4% women; median age 59 years old. The respective median ADDQoL and DTSQs scores were - 2.2 (interval interquartile range (IQR) - 3.9, - 0.8) (range from - 9 maximum negative impact to + 3 maximum positive impact) and 30(IQR22-36) (range from 0 maximum dissatisfaction to 36 maximum satisfaction). K10 median score was 26(IQR18-35) (range from minimum score of 10 indicating no distress to maximum score of 50 indicating severe distress). Rural dwelling, lack of exercise, current smoking, diabetic complications, injectable diabetes treatment, and previous COVID-19 infection were all associated with significantly worse ADDQoL, DTSQs, and K10 score indicating greater distress. A significant worsening of ADDQoL scores followed onset of the pandemic with no significant change in DTSQs scores. CONCLUSION: During the COVID-19 pandemic, T2DM Lebanese patients experienced more negative impact of diabetes on QoL and mental health. Those infected with COVID-19 also reported worse QoL, treatment satisfaction and mental health. This highlights the need for community and individual support.


Subject(s)
COVID-19/psychology , Diabetes Mellitus, Type 2/psychology , Mental Health , Psychological Distress , Quality of Life/psychology , Diabetes Mellitus, Type 2/drug therapy , Female , Humans , Hypoglycemic Agents/therapeutic use , Lebanon , Male , Middle Aged , Pandemics , Patient Reported Outcome Measures , Patient Satisfaction
14.
Lancet ; 398(10313): 1837-1850, 2021 11 13.
Article in English | MEDLINE | ID: covidwho-1510434

ABSTRACT

Type 1 diabetes is on the rise globally; however, the burden of mortality remains disproportionate in low-income and middle-income countries (LMICs). As 2021 marks 100 years since the discovery of insulin, we revisit progress, global burden of type 1 diabetes trends, and understanding of the pathogenesis and management practices related to the disease. Despite much progress, inequities in access and availability of insulin formulations persist and are reflected in differences in survival and morbidity patterns related to the disease. Some of these inequities have also been exacerbated by health-system challenges during the COVID-19 pandemic. There is a clear opportunity to improve access to insulin and related essential technologies for improved management of type 1 diabetes in LMICs, especially as a part of universal health coverage. These improvements will require concerted action and investments in human resources, community engagement, and education for the timely diagnosis and management of type 1 diabetes, as well as adequate health-care financing. Further research in LMICs, especially those in Africa, is needed to improve our understanding of the burden, risk factors, and implementation strategies for managing type 1 diabetes.


Subject(s)
Developing Countries , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 1/pathology , Diabetes Mellitus, Type 1/therapy , Global Burden of Disease/trends , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Adolescent , Child , Child, Preschool , Disease Management , History, 20th Century , History, 21st Century , Humans , Hypoglycemic Agents/economics , Hypoglycemic Agents/history , Insulin/economics , Insulin/history , Life Expectancy , Universal Health Insurance
15.
Br J Community Nurs ; 26(11): 544-552, 2021 Nov 02.
Article in English | MEDLINE | ID: covidwho-1506202

ABSTRACT

Type 1 diabetes is a lifelong condition which affects all age ranges, for reasons unknown, and the UK has one of the highest incidences of this complex condition in the world. Type 1 diabetes is caused by autoimmune damage to the insulin-producing ß-cells found in the pancreatic islet cells, leading to severe insulin deficiency. People with diabetes need to achieve a target glyosylated haemoglobin level to avoid macro- and microvascular complications, but there is the associated risk of hypoglycaemic events. These can vary in severity and consequences but will likely always cause worry for the person living with diabetes. There are many risk factors and reasons to be explored when looking at hypoglycaemia. This case study explores the nursing interventions that can be safely worked through and prioritised, within the community setting, to allow people with diabetes to be safe from severe hypoglycaemia, thus improving their quality of life and safety, as well as reducing costs for the NHS.


Subject(s)
Blood Glucose Self-Monitoring/methods , Diabetes Mellitus, Type 1/nursing , Glycated Hemoglobin A/analysis , Hypoglycemia/prevention & control , Hypoglycemic Agents/administration & dosage , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/drug therapy , Humans , Hypoglycemia/etiology , Hypoglycemia/nursing , Hypoglycemic Agents/therapeutic use , Quality of Life
16.
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.
Front Endocrinol (Lausanne) ; 12: 731974, 2021.
Article in English | MEDLINE | ID: covidwho-1485049

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a worldwide epidemic. It spreads very fast and hits people of all ages, especially patients with underlying diseases such as diabetes. In this review, we focus on the influences of diabetes on the outcome of SARS-CoV-2 infection and the involved mechanisms including lung dysfunction, immune disorder, abnormal expression of angiotensin-converting enzyme 2 (ACE2), overactivation of mechanistic target of rapamycin (mTOR) signaling pathway, and increased furin level. On the other hand, SARS-CoV-2 may trigger the development of diabetes. It causes the damage of pancreatic ß cells, which is probably mediated by ACE2 protein in the islets. Furthermore, SARS-CoV-2 may aggravate insulin resistance through attacking other metabolic organs. Of note, certain anti-diabetic drugs (OADs), such as peroxisome proliferator-activated receptor γ (PPARγ) activator and glucagon-like peptide 1 receptor (GLP-1R) agonist, have been shown to upregulate ACE2 in animal models, which may increase the risk of SARS-CoV-2 infection. However, Metformin, as a first-line medicine for the treatment of type 2 diabetes mellitus (T2DM), may be a potential drug benefiting diabetic patients with SARS-CoV-2 infection, probably via a suppression of mTOR signaling together with its anti-inflammatory and anti-fibrosis function in lung. Remarkably, another kind of OADs, dipeptidyl Peptidase 4 (DPP4) inhibitor, may also exert beneficial effects in this respect, probably via a prevention of SARS-CoV-2 binding to cells. Thus, it is of significant to identify appropriate OADs for the treatment of diabetes in the context of SARS-CoV-2 infections.


Subject(s)
COVID-19/epidemiology , COVID-19/metabolism , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/metabolism , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Humans , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Lung/drug effects , Lung/metabolism , T-Lymphocytes/drug effects , T-Lymphocytes/metabolism , TOR Serine-Threonine Kinases/antagonists & inhibitors , TOR Serine-Threonine Kinases/metabolism
19.
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
20.
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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