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1.
Med Hypotheses ; 158: 110739, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1560835

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an infectious diseases caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Now, it is pandemic over the world. SARS-CoV-2 often causes a "cytokine storm" in people with COVID-19, causing inflammatory lung damage and pneumonia, which eventually leads to death. Glucagon like peptide-1 (GLP-1) is well known as an incretin hormone responsible for regulation of blood glucose through its receptor. Beyond glycemic control, GLP-1 receptor agonists (GLP-1RAs) have promising anti-inflammatory actions in human and rodent pathological models. Recent studies proved that GLP-1RAs attenuate pulmonary inflammation, reduce cytokine production, and preserve lung function in mice and rats with experimental lung injury. Moreover, a thickened pulmonary vascular wall, an important characteristic of pulmonary arterial hypertension (PAH) was observed in the autopsy lung tissue of a COVID-19 patient. Thus GLP-1RAs may be a novel therapeutic strategy for combating this pandemic specifically for patient characteristics of PHA after COVID-19 infection.


Subject(s)
COVID-19 , Glucagon-Like Peptide-1 Receptor/agonists , Pulmonary Arterial Hypertension , Animals , COVID-19/complications , Humans , Lung , Mice , Pulmonary Arterial Hypertension/drug therapy , Pulmonary Arterial Hypertension/virology , Rats
3.
Diabetes Care ; 44(7): 1564-1572, 2021 07.
Article in English | MEDLINE | ID: covidwho-1405389

ABSTRACT

OBJECTIVE: To determine the respective associations of premorbid glucagon-like peptide-1 receptor agonist (GLP1-RA) and sodium-glucose cotransporter 2 inhibitor (SGLT2i) use, compared with premorbid dipeptidyl peptidase 4 inhibitor (DPP4i) use, with severity of outcomes in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RESEARCH DESIGN AND METHODS: We analyzed observational data from SARS-CoV-2-positive adults in the National COVID Cohort Collaborative (N3C), a multicenter, longitudinal U.S. cohort (January 2018-February 2021), with a prescription for GLP1-RA, SGLT2i, or DPP4i within 24 months of positive SARS-CoV-2 PCR test. The primary outcome was 60-day mortality, measured from positive SARS-CoV-2 test date. Secondary outcomes were total mortality during the observation period and emergency room visits, hospitalization, and mechanical ventilation within 14 days. Associations were quantified with odds ratios (ORs) estimated with targeted maximum likelihood estimation using a super learner approach, accounting for baseline characteristics. RESULTS: The study included 12,446 individuals (53.4% female, 62.5% White, mean ± SD age 58.6 ± 13.1 years). The 60-day mortality was 3.11% (387 of 12,446), with 2.06% (138 of 6,692) for GLP1-RA use, 2.32% (85 of 3,665) for SGLT2i use, and 5.67% (199 of 3,511) for DPP4i use. Both GLP1-RA and SGLT2i use were associated with lower 60-day mortality compared with DPP4i use (OR 0.54 [95% CI 0.37-0.80] and 0.66 [0.50-0.86], respectively). Use of both medications was also associated with decreased total mortality, emergency room visits, and hospitalizations. CONCLUSIONS: Among SARS-CoV-2-positive adults, premorbid GLP1-RA and SGLT2i use, compared with DPP4i use, was associated with lower odds of mortality and other adverse outcomes, although DPP4i users were older and generally sicker.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Glucagon-Like Peptide-1 Receptor/agonists , Sodium-Glucose Transporter 2 Inhibitors , Adult , Aged , COVID-19/diagnosis , Diabetes Mellitus, Type 2/drug therapy , Female , Humans , Longitudinal Studies , Male , Middle Aged , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , United States
4.
Expert Opin Drug Saf ; 20(11): 1309-1315, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1366929

ABSTRACT

INTRODUCTION: A number of anti-diabetic treatments have been favored during the continuing spread of the current SARS-CoV-2 pandemic. Glucagon like peptide-1 receptor agonists (GLP1-RAs) are a group of antidiabetic drugs, the glucose reducing effect of which is founded on augmenting glucose-dependent insulin secretion with concomitant reduction of glucagon secretion and delayed gastric emptying. Apart from their glucose lowering effects, GLP1-RAs also exert a plethora of pleiotropic activities in the form of anti-inflammatory, anti-thrombotic and anti-obesogenic properties, with beneficial cardiovascular and renal impact. All these make this class of drugs a preferred option for managing patients with type 2 diabetes (T2D), and potentially helpful in those with SARS-CoV2 infection. AREAS COVERED: In the present article we propose a hypothetical molecular mechanism by which GLP1-RAs may interact with SARS-CoV-2 activity. EXPERT OPINION: The beneficial properties of GLP1-RAs may be of specific importance during COVID-19 infection for the most fragile patients with chronic comorbid conditions such as T2D, and those at higher cardiovascular and renal disease risk. Yet, further studies are needed to confirm our hypothesis and preliminary findings available in the literature.


Subject(s)
COVID-19/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide-1 Receptor/agonists , Hypoglycemic Agents/therapeutic use , Incretins/therapeutic use , Animals , COVID-19/epidemiology , COVID-19/metabolism , COVID-19/virology , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/metabolism , Glucagon-Like Peptide-1 Receptor/metabolism , Humans , Hypoglycemic Agents/adverse effects , Incretins/adverse effects , Signal Transduction , Treatment Outcome
5.
Expert Rev Anti Infect Ther ; 20(3): 373-381, 2022 03.
Article in English | MEDLINE | ID: covidwho-1341075

ABSTRACT

INTRODUCTION: Understanding the pathogenesis and risk factors to control the coronavirus disease 2019 (COVID-19) is necessary. Due to the importance of the inflammatory pathways in the pathogenesis of COVID-19 patients, evaluating the effects of anti-inflammatory medications is important. Glucagon-like peptide 1 receptor agonist (GLP-1 RA) is awell-known glucose-lowering agent with anti-inflammatory effects. AREAS COVERED: Resources were extracted from the PubMed database, using keywords such as glucagon-like peptide-1, GLP-1 RA, SARS-CoV-2, COVID-19, inflammation, in April2021. In this review, the effects of GLP-1RA in reducing inflammation and modifying risk factors of COVID-19 severe complications are discussed. However, GLP-1 is degraded by DPP-4 with aplasma half-life of about 2-5 minutes, which makes it difficult to measure GLP-1 plasma level in clinical settings. EXPERT OPINION: Since no definitive treatment is available for COVID-19 so far, determining promising targets to design and/or repurpose effective medications is necessary.


Subject(s)
COVID-19 , Glucagon-Like Peptide 1 , Glucagon-Like Peptide-1 Receptor/agonists , Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Glucagon-Like Peptide 1/blood , Humans , SARS-CoV-2
7.
Int J Mol Sci ; 22(14)2021 Jul 16.
Article in English | MEDLINE | ID: covidwho-1314668

ABSTRACT

COVID-19 infection poses an important clinical therapeutic problem, especially in patients with coexistent diseases such as type 2 diabetes. Potential pathogenetic links between COVID-19 and diabetes include inflammation, effects on glucose homeostasis, haemoglobin deoxygenation, altered immune status and activation of the renin-angiotensin-aldosterone system (RAAS). Moreover, drugs often used in the clinical care of diabetes (dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, metformin and insulin) may influence the course of SARS-CoV-2 infection, so it is very important to verify their effectiveness and safety. This review summarises the new advances in diabetes therapy and COVID-19 and provides clinical recommendations that are essential for medical doctors and for patients suffering from type 2 diabetes.


Subject(s)
COVID-19/therapy , Diabetes Mellitus, Type 2/therapy , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/complications , COVID-19/epidemiology , COVID-19/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/virology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Glucagon-Like Peptide-1 Receptor/agonists , Humans , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Metformin/therapeutic use , SARS-CoV-2/isolation & purification , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
8.
Cell Metab ; 33(4): 692-699, 2021 04 06.
Article in English | MEDLINE | ID: covidwho-1298657

ABSTRACT

Marking insulin's centennial, we share stories of researchers and clinicians whose seminal work has advanced our understanding of insulin, islet biology, insulin resistance, and diabetes. The past century of pursuing the "hormone of hormones" and advancing diabetes therapies is replete with stories of collaboration, perseverance, and triumph.


Subject(s)
Diabetes Mellitus/drug therapy , Insulin/therapeutic use , Biomedical Research/history , Cell- and Tissue-Based Therapy , Drug Delivery Systems , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptide-1 Receptor/metabolism , History, 20th Century , History, 21st Century , Humans , Insulin/chemistry , Insulin/metabolism , Insulin Resistance , Insulin-Secreting Cells/cytology , Insulin-Secreting Cells/metabolism
9.
Diabetes Obes Metab ; 23(4): 910-915, 2021 04.
Article in English | MEDLINE | ID: covidwho-1028904

ABSTRACT

AIM: To estimate the proportion of individuals with type 2 diabetes mellitus (T2DM) undergoing changes in glucose-lowering therapy in 2019 and 2020. METHOD: Individuals with T2DM who had at least one consultation in one of 940 general (including diabetologist) practices in Germany between January and July 2019 (N = 79 268) and between January and July 2020 (N = 85 046) were included. Therapy changes were defined as the prescription of new glucose-lowering drugs, with or without the discontinuation of previous treatments (therapy switch and add-on therapy, respectively). The number of T2DM patients with at least one medication regimen change was calculated for the periods 1 January to 14 March in 2019 and 2020, and for the periods 15 March to 31 July in 2019 and 2020. March 2020 corresponded to the beginning of the lockdown in Germany. RESULTS: Overall, there was a decrease in the number of patients with at least one medication regimen change in the period 15 March to 31 July 2019 compared with 15 March to 31 July 2020 (dipeptidyl peptidase-4 inhibitors: -15%; sodium-glucose co-transporter-2 inhibitors: -3%; glucagon-like peptide-1 receptor agonists: 0%; other oral glucose-lowering drugs: -6%; and insulin: -21%). CONCLUSIONS: The coronavirus disease-2019 (COVID-2019) pandemic had a strong impact on glucose-lowering drug use in T2DM patients in Germany. More research is warranted to further investigate the treatment and management of T2DM individuals during the COVID-19 era in Germany and elsewhere.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Drug Substitution/trends , Drug Therapy, Combination/trends , Female , Germany , Glucagon-Like Peptide-1 Receptor/agonists , Humans , Insulin/therapeutic use , Male , Middle Aged , SARS-CoV-2 , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Young Adult
10.
Clin Obes ; 11(2): e12439, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1015529

ABSTRACT

The aim of the present manuscript is to discuss on potential pros and cons of glucagon-like peptide-1 receptor agonists (GLP-1RAs) as glucose-lowering agents during COVID-19 pandemic, and what is more to evaluate them as potential candidates for the treatment of patients, affected by COVID-19 infection, with or even without diabetes mellitus type 2. Besides being important glucose-lowering agents, GLP-1RAs pose promising anti-inflammatory and anti-obesogenic properties, pulmonary protective effects, as well as beneficial impact on gut microbiome composition. Hence, taking everything previously mentioned into consideration, GLP-1RAs seem to be potential candidates for the treatment of patients, affected by COVID-19 infection, with or even without type 2 diabetes mellitus, as well as excellent antidiabetic (glucose-lowering) agents during COVID-19 pandemic times.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Glucagon-Like Peptide-1 Receptor/agonists , Hypoglycemic Agents/pharmacology , Obesity , COVID-19/drug therapy , COVID-19/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Drug Repositioning/methods , Humans , Obesity/drug therapy , Obesity/metabolism , Protective Agents/pharmacology , SARS-CoV-2
11.
J Diabetes Complications ; 34(12): 107723, 2020 12.
Article in English | MEDLINE | ID: covidwho-731824

ABSTRACT

Inflammation is implicated in the development and severity of the coronavirus disease 2019 (COVID-19), as well as in the pathophysiology of diabetes. Diabetes, especially when uncontrolled, is also recognized as an important risk factor for COVID-19 morbidity and mortality. Furthermore, certain inflammatory markers [i.e. C-reactive protein (CRP), interleukin-6 (IL-6) and ferritin] were reported as strong predictors of worse outcomes in COVID-19 positive patients. The same biomarkers have been associated with poor glycemic control. Therefore, achieving euglycemia in patients with diabetes is even more important in the era of the COVID-19 pandemic. Based on the above, it is clinically interesting to elucidate whether antidiabetic drugs may reduce inflammation, thus possibly minimizing the risk for COVID-19 development and severity. The present narrative review discusses the potential anti-inflammatory properties of certain antidiabetic drugs (i.e. metformin, pioglitazone, sitagliptin, linagliptin, vildagliptin, alogliptin, saxagliptin, liraglutide, dulaglutide, exenatide, lixisenatide, semaglutide, empagliflozin, dapagliflozin, canagliflozin), with a focus on CRP, IL-6 and ferritin.


Subject(s)
COVID-19/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Hypoglycemic Agents/therapeutic use , Inflammation/prevention & control , SARS-CoV-2 , Anti-Inflammatory Agents , COVID-19/physiopathology , COVID-19/prevention & control , Comorbidity , Diabetes Mellitus, Type 2/physiopathology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Glucagon-Like Peptide-1 Receptor/agonists , Humans , Metformin/therapeutic use , Pioglitazone/therapeutic use , Risk Factors , Sitagliptin Phosphate/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
12.
J Diabetes Investig ; 11(5): 1104-1114, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-724172

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a global pandemic that is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus-2. Data from several countries have shown higher morbidity and mortality among individuals with chronic metabolic diseases, such as diabetes mellitus. In this review, we explore the contributing factors for poorer prognosis in these individuals. As a significant proportion of patients with COVID-19 also have diabetes mellitus, this adds another layer of complexity to their management. We explore potential interactions between antidiabetic medications and renin-angiotensin-aldosterone system inhibitors with COVID-19. Suggested recommendations for the use of antidiabetic medications for COVID-19 patients with diabetes mellitus are provided. We also review pertinent clinical considerations in the management of diabetic ketoacidosis in COVID-19 patients. In addition, we aim to increase clinicians' awareness of the metabolic effects of promising drug therapies for COVID-19. Finally, we highlight the importance of timely vaccinations for patients with diabetes mellitus.


Subject(s)
COVID-19/immunology , Diabetes Complications/immunology , Diabetes Mellitus/immunology , Obesity/immunology , Antibodies, Monoclonal, Humanized/therapeutic use , Antiviral Agents/therapeutic use , Blood Glucose/metabolism , COVID-19/complications , COVID-19/drug therapy , COVID-19/metabolism , COVID-19 Vaccines/therapeutic use , Chloroquine/therapeutic use , Comorbidity , Diabetes Complications/drug therapy , Diabetes Complications/metabolism , Diabetes Complications/physiopathology , Diabetes Mellitus/drug therapy , Diabetes Mellitus/metabolism , Diabetes Mellitus/physiopathology , Diabetic Ketoacidosis/complications , Diabetic Ketoacidosis/therapy , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Drug Combinations , Glucagon-Like Peptide-1 Receptor/agonists , Glycemic Control , Humans , Hydroxychloroquine/therapeutic use , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Insulin Resistance , Insulin Secretion , Interferon Type I/therapeutic use , Lopinavir/therapeutic use , Lung/physiopathology , Metformin/therapeutic use , Obesity/complications , Obesity/metabolism , Obesity/physiopathology , Pancreas/metabolism , Ritonavir/therapeutic use , Severity of Illness Index , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sulfonylurea Compounds/therapeutic use , Thiazolidinediones/therapeutic use
13.
Cardiovasc Diabetol ; 19(1): 115, 2020 07 22.
Article in English | MEDLINE | ID: covidwho-662457

ABSTRACT

The coronavirus disease 2019 (COVID-19) has been declared as pandemic by the World Health Organization and is causing substantial morbidity and mortality all over the world. Type 2 diabetes, hypertension, and cardiovascular disease significantly increase the risk for hospitalization and death in COVID-19 patients. Hypoglycemia and hyperglycemia are both predictors for adverse outcomes in hospitalized patients. An optimized glycemic control should be pursued in patients with diabetes and SARS-CoV-2 infection in order to reduce the risk of severe COVID-19 course. Both insulin and GLP-1RAs have shown optimal glucose-lowering and anti-inflammatory effects in type 2 diabetic patients and may represent a valid therapeutic option to treat asymptomatic and non-critically ill COVID-19 diabetic patients.


Subject(s)
Betacoronavirus/pathogenicity , Blood Glucose/drug effects , Coronavirus Infections/therapy , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/administration & dosage , Incretins/administration & dosage , Insulin/administration & dosage , Pneumonia, Viral/therapy , Biomarkers/blood , Blood Glucose/metabolism , COVID-19 , Clinical Decision-Making , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Glucagon-Like Peptide-1 Receptor/agonists , Host Microbial Interactions , Humans , Hypoglycemic Agents/adverse effects , Incretins/adverse effects , Insulin/adverse effects , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Risk Assessment , Risk Factors , SARS-CoV-2 , Treatment Outcome
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