Noninsulin‐based antihyperglycemic medications in patients with diabetes and COVID‐19: A systematic review and meta‐analysis
Mahmoud Nassar, Hazem Abosheaishaa, Awadhesh Kumar Singh, Anoop Misra, Zachary Bloomgarden
Journal of Diabetes, doi:10.1111/1753-0407.13359
Background: Patients with diabetes are more likely to suffer COVID-19 complications. Using noninsulin antihyperglycemic medications (AGMs) during COVID-19 infection has proved challenging. In this study, we evaluate different noninsulin AGMs in patients with COVID-19. Methods: We searched Medline, Embase, Web of Science, and Cochrane on 24 January 2022. We used the following keywords (COVID-19) AND (diabetes mellitus) AND (antihyperglycemic agent). The inclusion criteria were studies reporting one or more of the outcomes. We excluded non-English articles, case reports, and literature reviews. Study outcomes were mortality, hospitalization, and intensive care unit (ICU) admission. Results: The use of metformin rather than other glucose-lowering medications was associated with statistically significant lower mortality (risk ratio [RR]: 0.60, 95% confidence interval [CI]: 0.47, 0.77, p < .001). Dipeptidyl peptidase-4 inhibitor (DPP-4i) use was associated with statistically significantly higher hospitalization risk (RR: 1.44, 95% CI: 1.23, 1.68, p < .001) and higher risk of ICU admissions and/or mechanical ventilation vs nonusers (RR: 1.24, 95% CI: 1.04, 1.48, p < .02). There was a statistically significant decrease in hospitalization for SGLT-2i users vs nonusers (RR: 0.89, 95% CI: 0.84-0.95, p < .001). Glucagon-like peptide-1 receptor agonist (GLP-1RA) use was associated with a statistically significant decrease in mortality (RR: 0.56, 95% CI: 0.42, 073, p < 0.001), ICU admission, and/or mechanical
CONFLICT OF INTEREST There is no conflict of interest to declare.
ETHICAL STATEMENT No human or animal studies were involved in this study.
PATIENT AND PUBLIC INVOLVEMENT SUBSECTION Patients and the public were not involved in any way in this study.
SUPPORTING INFORMATION Additional supporting information can be found online in the Supporting Information section at the end of this article.
References
Belancic, Kresovic, Troskot, Glucagon-like peptide-1 receptor agonists in the era of COVID-19: friend or foe?, Clin Obes,
doi:info:doi/10.1111/cob.12439Bonora, Avogaro, Fadini, Disentangling conflicting evidence on DPP-4 inhibitors and outcomes of COVID-19: narrative review and meta-analysis, J Endocrinol Investig,
doi:info:doi/10.1007/s40618-021-01515-6Chen, Yang, Cheng, Clinical characteristics and outcomes of patients with diabetes and COVID-19 in association with glucose-lowering medication, Diabetes Care,
doi:info:doi/10.2337/dc20-0660Elibol, Eren, Erdogan, Factors influencing on development of COVID-19 pneumonia and association with oral anti-diabetic drugs in hospitalized patients with diabetes mellitus, Prim Care Diabetes,
doi:info:doi/10.1016/j.pcd.2021.08.001Emral, Haymana, Demirci, Lower COVID-19 mortality in patients with type 2 diabetes mellitus taking dipeptidyl peptidase-4 inhibitors: results from a Turkish nationwide study, Diabetes Ther,
doi:info:doi/10.1007/s13300-021-01133-8Fadini, Morieri, Longato, Exposure to dipeptidyl-peptidase-4 inhibitors and COVID-19 among people with type 2 diabetes: a case-control study, Diabetes Obes Metab
Gabery, Salinas, Paulsen, Semaglutide lowers body weight in rodents via distributed neural pathways, JCI Insight
Ghany, Palacio, Dawkins, Metformin is associated with lower hospitalizations, mortality and severe coronavirus infection among elderly medicare minority patients in 8 states in USA, Diabetes Metab Syndr,
doi:info:doi/10.1016/j.dsx.2021.02.022Israelsen, Pottegard, Sandholdt, Madsbad, Thomsen et al., Comparable COVID-19 outcomes with current use of GLP-1 receptor agonists, DPP-4 inhibitors or SGLT-2 inhibitors among patients with diabetes who tested positive for SARS-CoV-2, Diabetes Obes Metab,
doi:info:doi/10.1111/dom.14329Jiang, Chen, Liu, Association of metformin with mortality or ARDS in patients with COVID-19 and type 2 diabetes: A retrospective cohort study, Diabetes Res Clin Pract,
doi:info:doi/10.1016/j.diabres.2020.108619Kahkoska, Abrahamsen, Alexander, Association between glucagon-like peptide 1 receptor agonist and sodiumglucose cotransporter 2 inhibitor use and COVID-19 outcomes, Diabetes Care,
doi:info:doi/10.2337/dc21-0065Katsiki, Gomez-Huelgas, Mikhailidis, Perez-Martinez, Narrative review on clinical considerations for patients with diabetes and COVID-19: more questions than answers, Int J Clin Pract,
doi:info:doi/10.1111/ijcp.14833Klemann, Wagner, Horsten, Cut to the chase: a review of CD26/dipeptidyl peptidase-4's (DPP4) entanglement in the immune system, Clin Exp Immunol,
doi:info:doi/10.1111/cei.12781Kosiborod, Esterline, Furtado, Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebocontrolled, phase 3 trial, Lancet Diabetes Endocrinol,
doi:info:doi/10.1016/S2213-8587(21)00180-7Luk, Yip, Zhang, Glucose-lowering drugs and outcome from COVID-19 among patients with type 2 diabetes mellitus: a population-wide analysis in Hong Kong, BMJ Open,
doi:info:doi/10.1136/bmjopen-2021-052310Luo, Qiu, Liu, Metformin treatment was associated with decreased mortality in COVID-19 patients with diabetes in a retrospective analysis, Am J Trop Med Hyg,
doi:info:doi/10.4269/ajtmh.20-0375Meijer, Hoekstra, Van Den Oever, Treatment with a DPP-4 inhibitor at time of hospital admission for COVID-19 is not associated with improved clinical outcomes: data from the COVID-PREDICT cohort study in The Netherlands, J Diabetes Metab Disord,
doi:info:doi/10.1007/s40200-021-00833-zMirani, Favacchio, Carrone, Impact of comorbidities and glycemia at admission and dipeptidyl peptidase 4 inhibitors in patients with type 2 diabetes with COVID-19: a case series from an academic hospital in Lombardy Italy, Diabetes Care
Movaqar, Abdoli, Aryan, Jazaeri, Meshkat, Metformin promotes autophagy activity and constrains HSV-1 replication in neuroblastoma cells, Gene Rep
Noh, Oh, Jeong, Filion, Yu et al., Association between DPP-4 inhibitors and COVID-19-related outcomes among patients with type 2 diabetes, Diabetes Care
Nyland, Raja-Khan, Bettermann, Diabetes, drug treatment, and mortality in COVID-19: a multinational retrospective cohort study, Diabetes,
doi:info:doi/10.2337/db21-0385Ong, Tan, Canete, Lim, Robles, Association between metformin use and mortality among patients with type 2 diabetes mellitus hospitalized for COVID-19 infection, J ASEAN Fed Endocr Soc,
doi:info:doi/10.15605/jafes.036.02.20Patoulias, Doumas, Dipeptidyl Peptidase-4 inhibitors and COVID-19-related deaths among patients with type 2 diabetes mellitus: a meta-analysis of observational studies, Endocrinol Metab,
doi:info:doi/10.3803/EnM.2021.1048Patoulias, Papadopoulos, Boulmpou, Doumas, Metaanalysis of the hallmark cardiovascular and renal outcome trials addressing the risk for respiratory tract infections with sodium-glucose co-transporter-2 inhibitors: implications for the COVID-19 pandemic, Diabetes Obes Metab,
doi:info:doi/10.1111/dom.14359Perez-Belmonte, Torres-Pena, Lopez-Carmona, Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study, BMC Med,
doi:info:doi/10.1186/s12916-020-01832-2Popovic, Papanas, Stoian, Rizvi, Janez et al., Use of novel antidiabetic agents in patients with type 2 diabetes and COVID-19: a critical review, Diabetes Ther,
doi:info:doi/10.1007/s13300-021-01170-3Rakhmat, Kusmala, Handayani, Dipeptidyl peptidase-4 (DPP-4) inhibitor and mortality in coronavirus disease 2019 (COVID-19) -a systematic review, meta-analysis, and meta-regression, Diabetes Metab Syndr,
doi:info:doi/10.1016/j.dsx.2021.03.027Ramos-Rinc On, Pérez-Belmonte, Carrasco, Fj, Cardiometabolic therapy and mortality in very old patients with diabetes hospitalized due to COVID-19, J Gerontol A Biol Sci Med Sci,
doi:info:doi/10.1093/gerona/glab124Shafiee, Athar, Nassar, Comparison of COVID-19 outcomes in patients with type 1 and type 2 diabetes: a systematic review and meta-analysis, Diabetes Metab Syndr,
doi:info:doi/10.1016/j.dsx.2022.102512Shang, Zhang, Leng, Assessment of diabetic cardiomyopathy by cardiovascular magnetic resonance T1 mapping: correlation with left-ventricular diastolic dysfunction and diabetic duration, J Diabetes Res,
doi:info:doi/10.1155/2017/9584278Silverii, Monami, Cernigliaro, Are diabetes and its medications risk factors for the development of COVID-19? Data from a population-based study in Sicily, Nutr Metab Cardiovasc Dis,
doi:info:doi/10.1016/j.numecd.2020.09.028Singh, Gillies, Singh, Prevalence of comorbidities and their association with mortality in patients with COVID-19: a systematic review and meta-analysis, Diabetes Obes Metab,
doi:info:doi/10.1111/dom.14124Solerte, 'addio, Trevisan, 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,
doi:info:doi/10.2337/dc20-1521Sourij, Aziz, Bräuer, COVID-19 fatality prediction in people with diabetes and prediabetes using a simple score upon hospital admission, Diabetes Obes Metab,
doi:info:doi/10.1111/dom.14256Valencia, Peiro, Lorenzo, Sanchez-Ferrer, Eckel et al., DPP4 and ACE2 in diabetes and COVID-19: therapeutic targets for cardiovascular complications?, Front Pharmacol,
doi:info:doi/10.3389/fphar.2020.01161Vankadari, Wilce, Emerging WuHan (COVID-19) coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26, Emerg Microbes Infect,
doi:info:doi/10.1080/22221751.2020.1739565Viby, Isidor, Buggeskov, Poulsen, Hansen et al., Glucagon-like peptide-1 (GLP-1) reduces mortality and improves lung function in a model of experimental obstructive lung disease in female mice, Endocrinology,
doi:info:doi/10.1210/en.2013-1666Wargny, Potier, Gourdy, Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study, Diabetologia,
doi:info:doi/10.1007/s00125-020-05351-wWong, Lui, Lui, Use of DPP4i reduced odds of clinical deterioration and hyperinflammatory syndrome in COVID-19 patients with type 2 diabetes: propensity score analysis of a territory-wide cohort in Hong Kong, Diabetes Metab,
doi:info:doi/10.1016/j.diabet.2021.101307Worldometers, Worldometers-Real Time World Statistics
Zhang, Dong, Martin, AMP-activated protein kinase phosphorylation of angiotensin-converting enzyme 2 in endothelium mitigates pulmonary hypertension, Am J Respir Crit Care Med,
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'abstract': '<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Patients '
'with diabetes are more likely to suffer COVID‐19 complications. Using noninsulin '
'antihyperglycemic medications (AGMs) during COVID‐19 infection has proved challenging. In '
'this study, we evaluate different noninsulin AGMs in patients with '
'COVID‐19.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We searched '
'Medline, Embase, Web of Science, and Cochrane on 24 January 2022. We used the following '
'keywords (COVID‐19) AND (diabetes mellitus) AND (antihyperglycemic agent). The inclusion '
'criteria were studies reporting one or more of the outcomes. We excluded non‐English '
'articles, case reports, and literature reviews. Study outcomes were mortality, '
'hospitalization, and intensive care unit (ICU) '
'admission.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The use of '
'metformin rather than other glucose‐lowering medications was associated with statistically '
'significant lower mortality (risk ratio [RR]: 0.60, 95% confidence interval [CI]: 0.47, 0.77, '
'<jats:italic>p</jats:italic>\xa0<\u2009.001). Dipeptidyl peptidase‐4 inhibitor (DPP‐4i) '
'use was associated with statistically significantly higher hospitalization risk (RR: 1.44, '
'95% CI: 1.23, 1.68, <jats:italic>p</jats:italic>\xa0<\u2009.001) and higher risk of ICU '
'admissions and/or mechanical ventilation vs nonusers (RR: 1.24, 95% CI: 1.04, 1.48, '
'<jats:italic>p</jats:italic>\xa0<\u2009.02). There was a statistically significant '
'decrease in hospitalization for SGLT‐2i users vs nonusers (RR: 0.89, 95% CI: 0.84–0.95, '
'<jats:italic>p</jats:italic>\xa0<\u2009.001). Glucagon‐like peptide‐1 receptor agonist '
'(GLP‐1RA) use was associated with a statistically significant decrease in mortality (RR: '
'0.56, 95% CI: 0.42, 073, <jats:italic>p</jats:italic>\xa0<\u20090.001), ICU admission, '
'and/or mechanical ventilation (RR: 0.79, 95% CI: 0.69–0.89, <jats:italic>p</jats:italic>\xa0'
'<\u2009.001), and hospitalization (RR: 0.73, 95% CI: 0.54, 0.98, '
'<jats:italic>p</jats:italic>\xa0=\u2009'
'.04).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>AGM use was '
'not associated with increased mortality. However, metformin and GLP‐1RA use reduced mortality '
'risk statistically significantly. DPP‐4i use was associated with a statistically significant '
'increase in the risk of hospitalization and admission to the ICU.</jats:p></jats:sec>',
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