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1.
BMC Nephrol ; 23(1): 117, 2022 03 24.
Article in English | MEDLINE | ID: covidwho-1770497

ABSTRACT

BACKGROUND: Host factors such as angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease, serine-subtype-2 (TMPRSS2) are important factors for SARS-CoV-2 infection. Clinical and pre-clinical studies demonstrated that RAAS-blocking agents can be safely used during a SARS-CoV-2 infection but it is unknown if DPP-4 inhibitors or SGLT2-blockers may promote COVID-19 by increasing the host viral entry enzymes ACE2 and TMPRSS2. METHODS: We investigated telmisartan, linagliptin and empagliflozin induced effects on renal and cardiac expression of ACE2, TMPRSS2 and key enzymes involved in RAAS (REN, AGTR2, AGT) under high-salt conditions in a non-diabetic experimental 5/6 nephrectomy (5/6 Nx) model. In the present study, the gene expression of Ace2, Tmprss2, Ren, Agtr2 and Agt was assessed with qRT-PCR and the protein expression of ACE2 and TMPRSS2 with immunohistochemistry in the following experimental groups: Sham + normal diet (ND) + placebo (PBO); 5/6Nx + ND + PBO; 5/6Nx + high salt-diet (HSD) + PBO; 5/6Nx + HSD + telmisartan; 5/6Nx + HSD + linagliptin; 5/6Nx + HSD + empagliflozin. RESULTS: In the kidney, the expression of Ace2 was not altered on mRNA level under disease and treatment conditions. The renal TMPRSS2 levels (mRNA and protein) were not affected, whereas the cardiac level was significantly increased in 5/6Nx rats. Intriguingly, the elevated TMPRSS2 protein expression in the heart was significantly normalized after treatment with telmisartan, linagliptin and empagliflozin. CONCLUSIONS: Our study indicated that there is no upregulation regarding host factors potentially promoting SARS-CoV-2 virus entry into host cells when the SGLT2-blocker empagliflozin, telmisartan and the DPP4-inhibitor blocker linagliptin are used. The results obtained in a preclinical, experimental non-diabetic kidney failure model need confirmation in ongoing interventional clinical trials.


Subject(s)
COVID-19 , Dipeptidyl-Peptidase IV Inhibitors , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , Animals , COVID-19/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Humans , Kidney/metabolism , Nephrectomy , Rats , SARS-CoV-2 , Sodium-Glucose Transporter 2 , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
2.
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
3.
Endocrinol Diabetes Nutr (Engl Ed) ; 69(3): 209-218, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1693492

ABSTRACT

BACKGROUND: This consensus aims to clarify the role of Dipeptidyl Peptidase-4 inhibitors (iDPP-4) in managing patients with diabetes during the COVID-19 pandemic. MATERIALS AND METHODS: A PubMed bibliographic search was carried out (December 2019-February 2021). Oxford methodology was used for the evaluation of evidence and possible recommendations were established by consensus. RESULTS: Diabetes appears to be an independent factor in COVID-19 disease (evidence 2b). No increased risk of contagion with iDPP-4 is demonstrated (evidence 2b), and its use has been shown to be safe (evidence 2b). The use of this drug may present a specific benefit in reducing mortality, particularly in in-hospital use (evidence 2a), reducing admission to intensive care units (evidence 2b) and the need for mechanical ventilation (evidence 2b). CONCLUSIONS: The use of iDPP-4 appears to be safe in patients with COVID-19, and quality studies are needed to clarify their possible advantages further.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Consensus , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Humans , Pandemics
4.
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
5.
Arch Med Res ; 53(2): 186-195, 2022 02.
Article in English | MEDLINE | ID: covidwho-1347493

ABSTRACT

BACKGROUND AND AIMS: During the current Coronavirus Disease 2019 (COVID-19) pandemic, patients with diabetes face disproportionately more. This study was performed to clarify anti-inflammatory effects of anti-diabetic agents on COVID-19 in patients with diabetes. METHODS AND RESULTS: Relevant literature was searched on 15 databases up to November 14, 2020 and was updated on April 13, 2021. The pooled ORs along with 95% CIs were calculated to evaluate combined effects. 31 studies with 66,914 patients were included in qualitative and quantitative synthesis. Meta-analysis showed that metformin was associated with a statistically significant lower mortality (pooled OR = 0.62, 95% CI, 0.50-0.76, p = 0.000) and poor composite outcomes (pooled OR = 0.83, 95% CI, 0.71-0.97, p = 0.022) in diabetic patients with COVID-19. Significance of slight lower mortality remained in sulfonylurea/glinides (pooled OR = 0.93, 95% CI, 0.89-0.98, p = 0.004), but of poor composite outcomes was not (pooled OR = 1.48, 95% CI, 0.61-3.60, p = 0.384). Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) were associated with statistically non-significant lower mortality (pooled OR = 0.95, 95% CI, 0.72-1.26, p = 0.739) or poor composite outcomes (pooled OR = 1.27, 95% CI, 0.91-1.77, p = 0.162) of COVID-19 in diabetic patients. CONCLUSION: Metformin might be beneficial in decreasing mortality and poor composite outcomes in diabetic patients infected with SARS-CoV-2. DPP-4 inhibitors, sulfonylurea/glinides, SGLT-2 inhibitors, and GLP-1RA would not seem to be adverse. There was insufficient evidence to conclude effects of other anti-diabetic agents. Limited by retrospective characteristics, with relative weak capability to verify causality, more prospective studies, especially RCTs are needed. REGISTRATION NUMBER: PROSPERO-CRD42020221951.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , COVID-19/drug therapy , Diabetes Mellitus, Type 2/complications , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Humans , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Prospective Studies , Retrospective Studies , SARS-CoV-2
6.
Endocrinol Metab (Seoul) ; 36(4): 904-908, 2021 08.
Article in English | MEDLINE | ID: covidwho-1328154

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic remains an unbeaten enemy. Unfortunately, no targeted treatment option is available. Patients with type 2 diabetes mellitus (T2DM) have increased odds for severe or fatal disease, as demonstrated in recent observational studies. There is an ongoing discussion regarding the impact of different antidiabetic drug classes on outcomes of interest among affected subjects. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been placed at the epicenter, since the DPP-4 enzyme seems to be implicated in the disease pathogenesis. Herein we present an updated meta-analysis of observational studies addressing the risk of COVID-19 death among patients with T2DM on prior DPP-4 inhibitor treatment. We pooled data from 10 observational studies, showing that DPP-4 inhibitors produce a non-significant decrease in the risk for COVID-19-related death. However, when administered in the inpatient setting, DPP-4 inhibitors decrease the risk for COVID-19-related death by 50%. Ongoing randomized controlled trials will shed further light.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/mortality , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Observational Studies as Topic/methods , COVID-19/blood , Diabetes Mellitus, Type 2/blood , Dipeptidyl Peptidase 4/blood , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Humans , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Mortality/trends
7.
Diabetes Metab Syndr ; 15(3): 777-782, 2021.
Article in English | MEDLINE | ID: covidwho-1163663

ABSTRACT

BACKGROUND AND AIMS: This study aims to synthesize evidence on dipeptidyl peptidase-4 (DPP-4) inhibitor and mortality in COVID-19 patients and factors affecting it. METHODS: We performed a systematic literature search from PubMed, Scopus, and Embase databases from inception of databases up until 7 March 2021. Studies that met all of the following criteria were included: 1) observational studies or randomized controlled trials that report COVID-19 patients, 2) reporting DPP-4 inhibitor use, 3) mortality, and 4) mortality based on DPP-4 inhibitor use. The exposure was DPP-4 inhibitor, defined as DPP-4 inhibitor use that started prior to COVID-19 hospitalization. The control group was patients with no exposure to DPP-4 inhibitor. The outcome was mortality. The pooled effect estimate was reported as risk ratio (RR). RESULTS: There were 4,477 patients from 9 studies in this systematic review and meta-analysis. 31% of (15%, 46%) the patients use DPP-4 inhibitor. Mortality occurs in 23% (15%, 31%) of the patients. DPP-4 inhibitor was associated with lower mortality in patients with COVID-19 (RR 0.76 [0.60, 0.97], p = 0.030, I2: 44.5%, p = 0.072). Meta-regression analysis showed that the association between DPP-4 inhibitor and mortality was significantly affected by metformin (RR 1.02 [1.00, 1.04], p = 0.048) and angiotensin converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB) use (RR 1.04 [1.01, 1.07], p = 0.006), but not age (p = 0.759), sex (reference: male, p = 0.148), and hypertension (p = 0.218). CONCLUSION: DPP-4 inhibitor use was associated with lower mortality in COVID-19 patients, and the association was weaker in patients who were also taking metformin and/or ACE inhibitors.


Subject(s)
COVID-19/mortality , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/complications , COVID-19/epidemiology , Comorbidity , Diabetes Mellitus/drug therapy , Diabetes Mellitus/epidemiology , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Female , Humans , Hypertension/drug therapy , Hypertension/epidemiology , Male , Metformin/therapeutic use , Mortality , Regression Analysis , SARS-CoV-2/drug effects , SARS-CoV-2/physiology
8.
Biochem Pharmacol ; 188: 114517, 2021 06.
Article in English | MEDLINE | ID: covidwho-1128904

ABSTRACT

Dipeptidyl peptidase (DPP)-4 inhibitors are a class of orally available, small molecule inhibitors that prolong the insulinotropic activity of the incretin hormone glucagon-like peptide-1 (GLP-1) and are highly effective for the treatment of Type-2 diabetes. DPP4 can also cleave several immunoregulatory peptides including chemokines. Emerging evidence continues to implicate DPP4 inhibitors as immunomodulators, with recent findings suggesting DPP4 inhibitors modify specific aspects of innate immunity. This review summarises recent insights into how DPP4 inhibitors could be implicated in endothelial, neutrophil and monocyte/macrophage mediated immunity. Additionally, this review highlights additional avenues of research with DPP4 inhibitors in the context of the COVID-19 pandemic.


Subject(s)
COVID-19/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Immunity, Innate/drug effects , SARS-CoV-2/drug effects , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , COVID-19/immunology , Dipeptidyl-Peptidase IV Inhibitors/chemistry , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Glucagon-Like Peptide 1/immunology , Humans , Immunity, Innate/immunology , Neutrophils/drug effects , Neutrophils/immunology , SARS-CoV-2/immunology
9.
Endocr Rev ; 41(3)2020 06 01.
Article in English | MEDLINE | ID: covidwho-1110054

ABSTRACT

Individuals with diabetes are at increased risk for bacterial, mycotic, parasitic, and viral infections. The severe acute respiratory syndrome (SARS)-CoV-2 (also referred to as COVID-19) coronavirus pandemic highlights the importance of understanding shared disease pathophysiology potentially informing therapeutic choices in individuals with type 2 diabetes (T2D). Two coronavirus receptor proteins, angiotensin-converting enzyme 2 (ACE2) and dipeptidyl peptidase-4 (DPP4) are also established transducers of metabolic signals and pathways regulating inflammation, renal and cardiovascular physiology, and glucose homeostasis. Moreover, glucose-lowering agents such as the DPP4 inhibitors, widely used in subjects with T2D, are known to modify the biological activities of multiple immunomodulatory substrates. Here, we review the basic and clinical science spanning the intersections of diabetes, coronavirus infections, ACE2, and DPP4 biology, highlighting clinical relevance and evolving areas of uncertainty underlying the pathophysiology and treatment of T2D in the context of coronavirus infection.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Pneumonia, Viral/complications , Angiotensin-Converting Enzyme 2 , Animals , COVID-19 , Coronavirus Infections/metabolism , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 2/metabolism , Dipeptidyl Peptidase 4/metabolism , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Gastrointestinal Tract/metabolism , Humans , Insulin/therapeutic use , Lung/metabolism , Obesity/complications , Obesity/metabolism , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/metabolism , Receptors, Coronavirus , Receptors, Virus/metabolism , Risk Factors , SARS-CoV-2 , Serine Endopeptidases/metabolism
10.
Arch Immunol Ther Exp (Warsz) ; 69(1): 1, 2021 Feb 02.
Article in English | MEDLINE | ID: covidwho-1059378

ABSTRACT

A novel coronavirus disease, COVID-19, has emerged as a global public health issue. Clinical course of disease significantly correlates with the occurrence of some comorbidities, among them type 2 diabetes. According to recent structural studies the dipeptidyl peptidase 4, a key molecule in the pathophysiology of diabetes, may influence the course of COVID-19. Since DPP4 inhibitors, gliptins, are widely used in diabetes patients, the exact role of DPP4 modulation in SARS-CoV-2 infection, at least in that group, urgently needs to be clarified. In this short review, we discuss this issue with more detail.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Diabetes Mellitus, Type 2/complications , Dipeptidyl Peptidase 4/metabolism , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , SARS-CoV-2/drug effects , Antiviral Agents/pharmacology , COVID-19/complications , COVID-19/enzymology , COVID-19/metabolism , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Humans
11.
Therapie ; 75(4): 327-333, 2020.
Article in English | MEDLINE | ID: covidwho-1005621

ABSTRACT

According to previous reports, diabetes seems to be a risk factor which worsens the serious clinical events caused by COVID-19. But is diabetes per se a risk factor that increases the probability of getting the virus? This paper will discuss this point. There are not many research data on antidiabetic drugs in this context. The potential influence of glucose-lowering agents on the severity of COVID-19 has not been described yet. Dipeptidylpeptidase-4 (DPP-4) is a cell surface protein ubiquitously expressed in many tissues and it is also a soluble molecule found in serum/plasma fluids. DPP-4 is involved in infection of cells by some viruses. This paper reviews data about the use of DPP-4 inhibitors and others diabetes drugs on COVID-19 patients. As such, no available evidence has yet suggested that glucose-lowering drugs - including those targeting DPP4-related pathways - produce any significant harm or benefit in the context of human infections. However, insulin must remain the first-choice agent in the management of critically ill-hospitalized patients, while it is recommended to suspend other agents in unstable patients. This paper provides related French and international recommendations for people with diabetes who got infected by COVID-19 and upholds that infections may alter glucose control and may require additional vigilance.


Subject(s)
Coronavirus Infections/epidemiology , Diabetes Mellitus/epidemiology , Hypoglycemic Agents/administration & dosage , Pneumonia, Viral/epidemiology , Animals , COVID-19 , Coronavirus Infections/physiopathology , Diabetes Mellitus/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/administration & dosage , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Humans , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/pharmacology , Insulin/administration & dosage , Pandemics , Pneumonia, Viral/physiopathology , Risk Factors , Severity of Illness Index
12.
Diabetes Metab Syndr ; 15(1): 159-167, 2021.
Article in English | MEDLINE | ID: covidwho-987529

ABSTRACT

BACKGROUND & AIMS: Several observational studies have recently reported the outcomes of non-insulin anti-diabetic agents (ADA) in patients with T2DM and coronavirus disease 2019 (COVID-19). We sought to review the literature to appraise the clinicians on these outcomes. METHODS: A literature search using the specific keywords was carried out in the database of PubMed, MedRxiv and Google Scholar up till December 11, 2020 applying Boolean method. Full text of all the relevant articles that reported the outcomes of ADA in patients with T2DM and COVID-19 were retrieved. Subsequently, an appraisal of literature report was narratively presented. RESULTS: Available studies that reported the outcomes of ADA are either case series or retrospective cohorts or prospective observational studies, in absence of the randomized controlled trials (RCTs). Results from these observational studies suggest that amongst all the non-insulin ADA, metformin users prior to the hospitalization had improved outcomes compared to the non-users. Data for dipeptidyl-peptidase-4 inhibitors (DPP-4i) are encouraging although inconsistent. No documentation of any harm or benefit has been observed for sulfonylureas (SUs), sodium glucose co-transporter-2 inhibitors (SGLT-2i) and glucagon-like peptide receptor agonists (GLP-1RAs). No data is yet available for pioglitazone. CONCLUSION: Metformin and DPP-4i should be continued in patients with T2DM until hospitalization or unless contraindicated. No evidence of harm suggests that SUs, SGLT-2i or GLP-1RAs may not be stopped unless very sick, hospitalized or contraindicated. The results from RCTs are needed to claim any meaningful benefit with either metformin or DPP-4i in patients with T2DM and COVID-19.


Subject(s)
COVID-19/drug therapy , COVID-19/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Hypoglycemic Agents/therapeutic use , Blood Glucose/drug effects , Blood Glucose/metabolism , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Humans , Hypoglycemic Agents/pharmacology , Metformin/pharmacology , Metformin/therapeutic use , Prospective Studies , Retrospective Studies , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
14.
Diabetes Metab Syndr ; 15(1): 33-38, 2021.
Article in English | MEDLINE | ID: covidwho-957019

ABSTRACT

BACKGROUND AND AIMS: There is limited data about the prognosis and impact of COVID-19 pneumonia on patients with diabetes mellitus (DM). We aimed to assess blood indices, ECG markers of sudden death and malignant arrhythmias on admission, and diabetes lowering drugs as possible predictors of adverse in-hospital outcome and COVID-19 pneumonia recovery status. METHODS: A retrospective study included patients with newly diagnosed COVID-19 pneumonia from August 20, to October 5, 2020. RESULTS: A total of 192 patients with COVID-19 pneumonia were included in the present study, of whom 67 patients had DM. Low lymphocytes % [0.4(0.1-0.9), P = .011] and QTc interval prolongation [0.4(0.1-0.8), P = .022] were associated with increased length of ICU stay. On the other hand, metformin use [0.3(0.2-4), P = .032] and DPP-4 inhibitors use [0.3(0.2-3), P = .040] were associated with decreased length of ICU stay. QTc interval prolongation [0.4(0.1-0.9), P = .017] was associated with increased length of hospital stay, while using metformin [0.4(0.2-3), P = .022] was associated with decreased length of hospital stay. Low lymphocytes % [0.5(0.4-1.6), P = .001], insulin use [0.4(0.3-5), P = .003], and old age [0.5(0.1-2.3), P = .025] were associated with extensive lung injury. The risk for in-hospital death was associated with high neutrophil% [1(1-1.4), P = .045], while metformin use was associated with decreased risk for in-hospital death [0.1(0.1-0.6), P = .025]. Insulin use [0.3(0.2-4), P = .013] was associated with partial recovery following acute COVID pneumonia. CONCLUSIONS: Metformin and DPP-4 inhibitors use were associated with favorable in-hospital outcomes, while insulin use was associated with extensive lung injury and post-acute COVID-19 pneumonia partial recovery.


Subject(s)
COVID-19/diagnosis , COVID-19/epidemiology , Diabetes Mellitus/diagnosis , Diabetes Mellitus/epidemiology , Hospitalization/trends , Recovery of Function/physiology , Adult , Aged , COVID-19/drug therapy , Diabetes Mellitus/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Humans , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Iraq , Metformin/pharmacology , Metformin/therapeutic use , Middle Aged , Prognosis , Recovery of Function/drug effects , Retrospective Studies , Treatment Outcome
15.
Acta Pharm ; 71(2): 175-184, 2021 Jun 01.
Article in English | MEDLINE | ID: covidwho-910385

ABSTRACT

Recently, an outbreak of a fatal coronavirus, SARS-CoV-2, has emerged from China and is rapidly spreading worldwide. Possible interaction of SARS-CoV-2 with DPP4 peptidase may partly contribute to the viral pathogenesis. An integrative bioinformatics approach starting with mining the biomedical literature for high confidence DPP4-protein/gene associations followed by functional analysis using network analysis and pathway enrichment was adopted. The results indicate that the identified DPP4 networks are highly enriched in viral processes required for viral entry and infection, and as a result, we propose DPP4 as an important putative target for the treatment of COVID-19. Additionally, our protein-chemical interaction networks identified important interactions between DPP4 and sitagliptin. We conclude that sitagliptin may be beneficial for the treatment of COVID-19 disease, either as monotherapy or in combination with other therapies, especially for diabetic patients and patients with pre-existing cardiovascular conditions who are already at higher risk of COVID-19 mortality.


Subject(s)
Coronavirus Infections/drug therapy , Dipeptidyl Peptidase 4/drug effects , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Pneumonia, Viral/drug therapy , Sitagliptin Phosphate/pharmacology , Sitagliptin Phosphate/therapeutic use , COVID-19 , Cardiovascular Diseases/complications , Cardiovascular Diseases/drug therapy , Computational Biology , Coronavirus Infections/complications , Crystallography, X-Ray , Data Mining , Diabetes Complications/drug therapy , Drug Delivery Systems , Drug Repositioning , Gene Regulatory Networks , Humans , Molecular Structure , Pandemics , Pneumonia, Viral/complications
16.
J Chin Med Assoc ; 83(8): 710-711, 2020 08.
Article in English | MEDLINE | ID: covidwho-733327

ABSTRACT

The pandemic infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is widely increasing the patients affiliated with coronavirus disease 2019 (COVID-19) from last December of 2019. It is reported that the entry receptor of SARS-CoV-2 has been confirmed to be angiotensin-converting enzyme 2 (ACE2). Notably, whether the ACE-related inhibitors or drugs modulated ACE2 activity in affecting the viral activity and disease severity of SARS-CoV-2 is still an open question. Dipeptidyl peptidase-4 (DDP-4), a well-known anti-diabetic drug, has been widely used to control the glycemic condition in patients with diabetes. In this article, we are focusing on the impact of ACE inhibitors (ACEI) and DPP4 inhibitors used on SARS-CoV-2 activity and discussions about those drugs that may be related to infectious condition of COVID-19 diseases.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/etiology , Diabetes Mellitus/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Pneumonia, Viral/etiology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , COVID-19 , Humans , Pandemics , SARS-CoV-2
17.
J Cell Mol Med ; 24(18): 10274-10278, 2020 09.
Article in English | MEDLINE | ID: covidwho-670250

ABSTRACT

With the outbreak of a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the public healthcare systems are facing great challenges. Coronavirus disease 2019 (COVID-19) could develop into severe pneumonia, acute respiratory distress syndrome and multi-organ failure. Remarkably, in addition to the respiratory symptoms, some COVID-19 patients also suffer from cardiovascular injuries. Dipeptidyl peptidase-4 (DPP-4) is a ubiquitous glycoprotein which could act both as a cell membrane-bound protein and a soluble enzymatic protein after cleavage and release into the circulation. Despite angiotensin-converting enzyme 2 (ACE2), the recently recognized receptor of SARS-CoV and SARS-CoV-2, which facilitated their entries into the host, DPP-4 has been identified as the receptor of middle east respiratory syndrome coronavirus (MERS-CoV). In the current review, we discussed the potential roles of DPP-4 in COVID-19 and the possible effects of DPP-4 inhibitors on cardiovascular system in patients with COVID-19.


Subject(s)
COVID-19/drug therapy , Cardiovascular Diseases/enzymology , Dipeptidyl Peptidase 4/metabolism , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Cardiovascular Diseases/virology , Host-Pathogen Interactions , Humans , SARS-CoV-2/physiology , Virus Internalization
18.
J Cardiovasc Pharmacol Ther ; 25(6): 494-496, 2020 11.
Article in English | MEDLINE | ID: covidwho-630976

ABSTRACT

The current coronavirus disease 2019 (COVID-19) pandemic has led the scientific community to breach new frontiers in the understanding of human physiology and disease pathogenesis. It has been hypothesized that the human dipeptidyl peptidase 4 (DPP4) enzyme receptor may be a functional target for the spike proteins of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Since DPP4-inhibitors are currently used for the treatment of patients with type-2 diabetes (T2DM), there is currently high interest in the possibility that these agents, or incretin-based therapies (IBTs) in general, may be of benefit against the new coronavirus infection. Diabetes is associated with increased COVID-19 severity and mortality, and accumulating evidence suggests that IBTs may favorably alter the clinical course of SARS-CoV-2 infection due to their inherent mechanisms of action. Further research into prognostic variables associated with various antidiabetic treatment regimens, and in particular the IBT, in patients with T2DM affected by the COVID-19 pandemic is therefore warranted.


Subject(s)
Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Incretins/therapeutic use , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Betacoronavirus , COVID-19 , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Glucagon-Like Peptide-1 Receptor/metabolism , Humans , Hypoglycemic Agents , Incretins/pharmacology , Inflammation Mediators/metabolism , Pandemics , SARS-CoV-2 , Severity of Illness Index
20.
Acta Diabetol ; 57(7): 779-783, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-549301

ABSTRACT

AIMS: SARS-CoV-2 causes severe respiratory syndrome (COVID-19) with high mortality due to a direct cytotoxic viral effect and a severe systemic inflammation. We are herein discussing a possible novel therapeutic tool for COVID-19. METHODS: Virus binds to the cell surface receptor ACE2; indeed, recent evidences suggested that SARS-CoV-2 may be using as co-receptor, when entering the cells, the same one used by MERS-Co-V, namely the DPP4/CD26 receptor. The aforementioned observation underlined that mechanism of cell entry is supposedly similar among different coronavirus, that the co-expression of ACE2 and DPP4/CD26 could identify those cells targeted by different human coronaviruses and that clinical complications may be similar. RESULTS: The DPP4 family/system was implicated in various physiological processes and diseases of the immune system, and DPP4/CD26 is variously expressed on epithelia and endothelia of the systemic vasculature, lung, kidney, small intestine and heart. In particular, DPP4 distribution in the human respiratory tract may facilitate the entrance of the virus into the airway tract itself and could contribute to the development of cytokine storm and immunopathology in causing fatal COVID-19 pneumonia. CONCLUSIONS: The use of DPP4 inhibitors, such as gliptins, in patients with COVID-19 with, or even without, type 2 diabetes, may offer a simple way to reduce the virus entry and replication into the airways and to hamper the sustained cytokine storm and inflammation within the lung in patients diagnosed with COVID-19 infection.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Dipeptidyl Peptidase 4/metabolism , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Lung/metabolism , Pneumonia, Viral/drug therapy , COVID-19 , Coronavirus Infections/enzymology , Dipeptidyl Peptidase 4/drug effects , Humans , Pandemics , Pneumonia, Viral/enzymology , SARS-CoV-2
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