Diabetes, Drug Treatment, and Mortality in COVID-19: A Multinational Retrospective Cohort Study
Tóm tắt
Patients with type 2 diabetes mellitus (T2DM) are at increased risk of severe coronavirus disease 2019 (COVID-19) outcomes possibly because of dysregulated inflammatory responses. Glucose-regulating medications, such as glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors, and pioglitazone, are known to have anti-inflammatory effects that may improve outcomes in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In a multinational retrospective cohort study, we used the TriNetX COVID-19 Research Network of 56 large health care organizations to examine these medications in relation to the incidence of hospital admissions, respiratory complications, and mortality within 28 days after a COVID-19 diagnosis. After matching for age, sex, race, ethnicity, BMI, and significant comorbidities, use of GLP-1R agonists and/or pioglitazone was associated with significant reductions in hospital admissions (GLP-1R: 15.7% vs. 23.5%, risk ratio [RR] 0.67 [95% CI 0.57–0.79; P < 0.001]; pioglitazone: 20.0% vs. 28.2%; RR 0.71 [95% CI 0.54–0.93; P = 0.01]). Use of GLP-1R agonists was also associated with reductions in respiratory complications (15.3% vs. 24.9%, RR 0.62 [95% CI 0.52–0.73]; P < 0.001) and incidence of mortality (1.9% vs. 3.3%, RR 0.58 [95% CI 0.35–0.97]; P = 0.04). Use of DPP-4 inhibitors was associated with a reduction in respiratory complications (24.0% vs. 29.2%, RR 0.82 [95% CI 0.74–0.90]; P < 0.001), and continued use of DPP-4 inhibitors after hospitalization was associated with a decrease in mortality compared with those who discontinued use (9% vs. 19%, RR 0.45 [95% CI 0.28–0.72]; P < 0.001). In conclusion, use of glucose-regulating medications, such as GLP-1R agonists, DPP-4 inhibitors, or pioglitazone, may improve COVID-19 outcomes for patients with T2DM; randomized clinical trials are needed to further investigate this possibility.
Từ khóa
Tài liệu tham khảo
Dong, 2020, An interactive web-based dashboard to track COVID-19 in real time, Lancet Infect Dis, 20, 533, 10.1016/S1473-3099(20)30120-1
Beigel, 2020, Remdesivir for the treatment of Covid-19–preliminary report. Reply, N Engl J Med, 383, 994, 10.1056/NEJMoa2007764
Beigel, 2020, Remdesivir for the treatment of Covid-19–final report, N Engl J Med, 383, 1813, 10.1056/NEJMoa2007764
World Health Organization . WHO Welcomes Preliminary Results About Dexamethasone Use in Treating Critically Ill COVID-19 Patients. Accessed 25 June 2020. Available from: https://www.who.int/news/item/16-06-2020-who-welcomes-preliminary-results-about-dexamethasne-use-in-treating- critically-ill-covid-19-patients
Aggarwal, 2020, Clinical and epidemiological features of SARS-CoV-2 patients in SARI ward of a tertiary care centre in New Delhi, J Assoc Physicians India, 68, 19
Chung, 2020, The risk of diabetes on clinical outcomes in patients with coronavirus disease 2019: a retrospective cohort study, Diabetes Metab J, 44, 405, 10.4093/dmj.2020.0105
Udwadia, 2020, Prognostic factors for adverse outcomes in COVID-19 infection, J Assoc Physicians India, 68, 62
Wu, 2020, Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention, JAMA, 323, 1239, 10.1001/jama.2020.2648
Barron, 2020, Associations of type 1 and type 2 diabetes with COVID-19-related mortality in England: a whole-population study, Lancet Diabetes Endocrinol, 8, 813, 10.1016/S2213-8587(20)30272-2
Guo, 2020, Diabetes is a risk factor for the progression and prognosis of COVID-19, Diabetes Metab Res Rev, 36, e3319, 10.1002/dmrr.3319
Sun, 2020, Cytokine storm intervention in the early stages of COVID-19 pneumonia, Cytokine Growth Factor Rev, 53, 38, 10.1016/j.cytogfr.2020.04.002
Montefusco, 2021, Acute and long-term disruption of glycometabolic control after SARS-CoV-2 infection, Nat Metab, 3, 774, 10.1038/s42255-021-00407-6
Bai, 2021, The active GLP-1 analogue liraglutide alleviates H9N2 influenza virus-induced acute lung injury in mice, Microb Pathog, 150, 104645, 10.1016/j.micpath.2020.104645
Fandiño, 2018, Liraglutide enhances the activity of the ACE-2/Ang(1-7)/Mas receptor pathway in lungs of male pups from food-restricted mothers and prevents the reduction of SP-A, Int J Endocrinol, 2018, 6920620, 10.1155/2018/6920620
Romaní-Pérez, 2015, Activation of the GLP-1 receptor by liraglutide increases ACE2 expression, reversing right ventricle hypertrophy, and improving the production of SP-A and SP-B in the lungs of type 1 diabetes rats, Endocrinology, 156, 3559, 10.1210/en.2014-1685
Sato, 2020, GLP-1 receptor signaling differentially modifies the outcomes of sterile vs viral pulmonary inflammation in male mice, Endocrinology, 161, bqaa201, 10.1210/endocr/bqaa201
Zhang, 2015, Preservation of glucagon-like peptide-1 level attenuates angiotensin II-Induced tissue fibrosis by altering AT1/AT 2 receptor expression and angiotensin-converting enzyme 2 activity in rat heart, Cardiovasc Drugs Ther, 29, 243, 10.1007/s10557-015-6592-7
Sánchez-Aguilar, 2019, Rosiglitazone, a ligand to PPARγ, improves blood pressure and vascular function through renin-angiotensin system regulation, PPAR Res, 2019, 1371758, 10.1155/2019/1371758
Zhang, 2014, Pioglitazone upregulates angiotensin converting enzyme 2 expression in insulin-sensitive tissues in rats with high-fat diet-induced nonalcoholic steatohepatitis, ScientificWorldJournal, 2014, 603409
Akhtar, 2020, Pharmacotherapy in COVID-19 patients: a review of ACE2-raising drugs and their clinical safety, J Drug Target, 28, 683, 10.1080/1061186X.2020.1797754
Lim, 2020, Diabetes drugs and stroke risk: intensive versus conventional glucose-lowering strategies, and implications of recent cardiovascular outcome trials, Diabetes Obes Metab, 22, 6, 10.1111/dom.13850
Williams, 2020, Diabetes and novel coronavirus infection: implications for treatment, Diabetes Ther, 11, 1915, 10.1007/s13300-020-00858-2
Carboni, 2020, Can pioglitazone be potentially useful therapeutically in treating patients with COVID-19?, Med Hypotheses, 140, 109776, 10.1016/j.mehy.2020.109776
Ciavarella, 2020, Pharmacological (or synthetic) and nutritional agonists of PPAR-γ as candidates for cytokine storm modulation in COVID-19 disease, Molecules, 25, E2076, 10.3390/molecules25092076
Iacobellis, 2020, COVID-19 and diabetes: can DPP4 inhibition play a role?, Diabetes Res Clin Pract, 162, 108125, 10.1016/j.diabres.2020.108125
Montastruc, 2020, Pharmacological characteristics of patients infected with SARS-Cov-2 admitted to intensive care unit in south of France, Therapie, 75, 381, 10.1016/j.therap.2020.05.005
Katsiki, 2020, Anti-inflammatory properties of antidiabetic drugs: a “promised land” in the COVID-19 era?, J Diabetes Complications, 34, 107723, 10.1016/j.jdiacomp.2020.107723
Solerte, 2020, Dipeptidyl peptidase-4 (DPP4) inhibition in COVID-19, Acta Diabetol, 57, 779, 10.1007/s00592-020-01539-z
Prasad-Reddy, 2015, A clinical review of GLP-1 receptor agonists: efficacy and safety in diabetes and beyond, Drugs Context, 4, 212283, 10.7573/dic.212283
Wadden, 2013, Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study, Int J Obes, 37, 1443, 10.1038/ijo.2013.120
Zaccardi, 2016, Benefits and harms of once-weekly glucagon-like peptide-1 receptor agonist treatments: a systematic review and network meta-analysis, Ann Intern Med, 164, 102, 10.7326/M15-1432
Andersen, 2018, Glucagon-like peptide 1 in health and disease, Nat Rev Endocrinol, 14, 390, 10.1038/s41574-018-0016-2
Bramante, Non-alcoholic fatty liver disease (NAFLD) and risk of hospitalization for Covid-19, 10.1101/2020.09.01.20185850
Hussein, 2018, Efficacy and safety of sodium-glucose cotransporter 2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in patients with type 2 diabetes: a systematic review and network meta-analysis study protocol, BMJ Open, 8, e023206, 10.1136/bmjopen-2018-023206
Hussein, 2019, Cardiovascular efficacy and safety of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists: a systematic review and network meta-analysis, Diabet Med, 36, 444, 10.1111/dme.13898
Li, 2018, Glucagon-like peptide-1 receptor agonists and cardiovascular risk reduction in type 2 diabetes mellitus: is it a class effect?, Curr Cardiol Rep, 20, 113, 10.1007/s11886-018-1051-2
Savchenko, 2019, Liraglutide exerts an anti-inflammatory action in obese patients with type 2 diabetes, Rom J Intern Med, 57, 233
Li, 2020, Semaglutide attenuates excessive exercise-induced myocardial injury through inhibiting oxidative stress and inflammation in rats, Life Sci, 250, 117531, 10.1016/j.lfs.2020.117531
Tan, 2019, Liraglutide and semaglutide attenuate inflammatory cytokines interferongamma, tumor necrosis factor-alpha, and interleukin-6: possible mechanism of decreasing cardiovascular risk in diabetes mellitus, J Am Coll Cardiol, 73, 1866, 10.1016/S0735-1097(19)32472-6
Raj, 2013, Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC, Nature, 495, 251, 10.1038/nature12005
Lebovitz, 2001, Insulin resistance and its treatment by thiazolidinediones, Recent Prog Horm Res, 56, 265, 10.1210/rp.56.1.265
Stacey, 2017, Using EHR data extraction to streamline the clinical trial process, Clin Res (Alex), 4, 2
Stapff, 2017, Use of electronic health data in clinical development, Pharm Ind, 79, 204
Kumar, 2020, Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis, Diabetes Metab Syndr, 14, 535, 10.1016/j.dsx.2020.04.044
Alberti, 2004, Type 2 diabetes in the young: the evolving epidemic: the International Diabetes Federation consensus workshop, Diabetes Care, 27, 1798, 10.2337/diacare.27.7.1798
Williamson, 2020, Factors associated with COVID-19-related death using OpenSAFELY, Nature, 584, 430, 10.1038/s41586-020-2521-4
Guan, 2020, Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis, Eur Respir J, 55, 2000547, 10.1183/13993003.00547-2020
Solerte, 2020, Sitagliptin Treatment at the time of hospitalization was associated with reduced mortality in patients with type 2 diabetes and COVID-19: a multicenter, case-control, retrospective, observational study, Diabetes Care, 43, 2999, 10.2337/dc20-1521