Infection Rates and Impact of Glucose Lowering Medications on the Clinical Course of COVID-19 in People with Type 2 Diabetes: A Retrospective Observational Study
Francesca Mannucci, Giacomo Vitturi, Luca Benacchio, Luca Gino Sbrogiò, Francesca Bano, Annunziata Lapolla, Francesco Piarulli, Maria Cecilia Giron, Angelo Avogaro, Gian Paolo Fadini
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, doi:10.2147/dmso.s385646
Diabetes is a risk factor for COVID-19 severity, but the role played by glucose lowering medications (GLM) is still unclear. The aim of this study was to assess infection rates and outcomes of COVID-19 (hospitalization and mortality) in adults with diabetes assisted by the Local Health Unit of Padua (North-East Italy) according to the ongoing GLM. Patients and Methods: People with diabetes were identified using administrative claims, while those with SARS-CoV-2 infection were detected by cross referencing with the local COVID-19 surveillance registry. A multivariate logistic regression model was used to verify the association between GLM classes and the outcome. Results: SARS-CoV-2 infection rates were marginally but significantly higher in individuals with diabetes as compared to those without diabetes (RR 1.04, p = 0.043), though such relative 4% increase may be irrelevant from a clinical and epidemiological perspective. 1923 individuals with GLM-treated diabetes were diagnosed with COVID-19; 456 patients were hospitalized and 167 died. Those treated with insulin had a significantly higher risk of hospitalizations for COVID-19 (OR 1.48 p < 0.01) as were those treated with sulphonylureas/glinides (OR 1.34, p = 0.02). Insulin use was also significantly associated with higher mortality (OR 1.90, p < 0.01). Use of metformin was significantly associated with lower death rates (OR 0.62, p = 0.02). The association of other GLM classes with the outcome was not significant. Conclusion: Diabetes does not appear to modify the risk of SARS-CoV-2 infection in a clinically meaningful way, but strongly increases the rates of hospitalization and death. Insulin use was associated with worse outcomes, whereas metformin use was associated with lower mortality.
References
Bonora, Fedeli, Schievano, SARS-CoV-2 and COVID-19 in diabetes mellitus. Population-based study on ascertained infections, hospital admissions and mortality in an Italian region with ~5 million inhabitants and~250,000 diabetic people, Nutr Metab Cardiovasc Dis,
doi:10.1016/j.numecd.2021.06.010Boye, Erdemir, Zimmerman, Risk factors associated with COVID-19 hospitalization and mortality: a large claims-based analysis among people with type 2 diabetes mellitus in the United States, Diabetes Ther,
doi:10.1007/s13300-021-01110-1Bramante, Huling, Tignanelli, Randomized trial of metformin, ivermectin, and fluvoxamine for Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2201662Diabetes, None, Metabolic Syndrome and Obesity: Targets and Therapy
Fadini, Morieri, Longato, Avogaro, Prevalence and impact of diabetes among people infected with SARS-CoV-2, J Endocrinol Invest,
doi:10.1007/s40618-020-01236-2Fadini, Morieri, Longato, Exposure to dipeptidyl-peptidase-4 inhibitors and COVID -19 among people with type 2 diabetes: a casecontrol study, Diabetes Obes Metab,
doi:10.1111/dom.14097Goldstein, Lee, Demographic perspectives on the mortality of COVID-19 and other epidemics, Proc Natl Acad Sci U S A,
doi:10.1073/pnas.2006392117Hui, Azhar, Madani, The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health -the latest 2019 novel coronavirus outbreak in Wuhan, China, Int J Infect Dis,
doi:10.1016/j.ijid.2020.01.009Khunti, Knighton, Zaccardi, Prescription of glucose-lowering therapies and risk of COVID-19 mortality in people with type 2 diabetes: a nationwide observational study in England, Lancet Diabetes Endocrinol,
doi:10.1016/S2213-8587(21)00050-4Kumar, Arora, Sharma, Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis, Diabetes Metab Syndr,
doi:10.1016/j.dsx.2020.04.044Lukito, Pranata, Henrina, Lim, Lawrensia et al., The effect of metformin consumption on mortality in hospitalized COVID-19 patients: a systematic review and meta-analysis, Diabetes Metab Syndr,
doi:10.1016/j.dsx.2020.11.006Montopoli, Zumerle, Vettor, Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532), Ann Oncol,
doi:10.1016/j.annonc.2020.04.479Schlesinger, Neuenschwander, Lang, Risk phenotypes of diabetes and association with COVID-19 severity and death: a living systematic review and meta-analysis, Diabetologia,
doi:10.1007/s00125-021-05458-8Solerte, '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, Dia Care,
doi:10.2337/dc20-1521Varikasuvu, Dutt, Thangappazham, Varshney, Diabetes and COVID-19: a pooled analysis related to disease severity and mortality, Prim Care Diabetes,
doi:10.1016/j.pcd.2020.08.015Wiersinga, Rhodes, Cheng, Peacock, Prescott, Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review, JAMA,
doi:10.1001/jama.2020.12839Yu, Li, Sun, Wang, Insulin treatment is associated with increased mortality in patients with COVID-19 and type 2 diabetes, Cell Metab,
doi:10.1016/j.cmet.2020.11.014{ 'indexed': { 'date-parts': [[2022, 10, 10]],
'date-time': '2022-10-10T06:12:27Z',
'timestamp': 1665382347448},
'reference-count': 22,
'publisher': 'Informa UK Limited',
'license': [ { 'start': { 'date-parts': [[2022, 10, 1]],
'date-time': '2022-10-01T00:00:00Z',
'timestamp': 1664582400000},
'content-version': 'unspecified',
'delay-in-days': 0,
'URL': 'https://creativecommons.org/licenses/by-nc/3.0/'}],
'content-domain': {'domain': [], 'crossmark-restriction': False},
'DOI': '10.2147/dmso.s385646',
'type': 'journal-article',
'created': { 'date-parts': [[2022, 10, 10]],
'date-time': '2022-10-10T05:55:10Z',
'timestamp': 1665381310000},
'page': '3093-3101',
'source': 'Crossref',
'is-referenced-by-count': 0,
'title': 'Infection Rates and Impact of Glucose Lowering Medications on the Clinical Course of COVID-19 in '
'People with Type 2 Diabetes: A Retrospective Observational Study',
'prefix': '10.2147',
'volume': 'Volume 15',
'author': [ {'given': 'Francesca', 'family': 'Mannucci', 'sequence': 'first', 'affiliation': []},
{'given': 'Giacomo', 'family': 'Vitturi', 'sequence': 'additional', 'affiliation': []},
{'given': 'Luca', 'family': 'Benacchio', 'sequence': 'additional', 'affiliation': []},
{'given': 'Luca Gino', 'family': 'Sbrogiò', 'sequence': 'additional', 'affiliation': []},
{'given': 'Francesca', 'family': 'Bano', 'sequence': 'additional', 'affiliation': []},
{'given': 'Annunziata', 'family': 'Lapolla', 'sequence': 'additional', 'affiliation': []},
{'given': 'Francesco', 'family': 'Piarulli', 'sequence': 'additional', 'affiliation': []},
{'given': 'Maria Cecilia', 'family': 'Giron', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-1177-0516',
'authenticated-orcid': True,
'given': 'Angelo',
'family': 'Avogaro',
'sequence': 'additional',
'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-6510-2097',
'authenticated-orcid': True,
'given': 'Gian Paolo',
'family': 'Fadini',
'sequence': 'additional',
'affiliation': []}],
'member': '301',
'published-online': {'date-parts': [[2022, 10]]},
'reference': [ { 'key': 'ref1',
'doi-asserted-by': 'publisher',
'first-page': '264',
'DOI': '10.1016/j.ijid.2020.01.009',
'volume': '91',
'author': 'Hui',
'year': '2020',
'journal-title': 'Int J Infect Dis'},
{ 'key': 'ref2',
'doi-asserted-by': 'publisher',
'first-page': '181',
'DOI': '10.1038/s41579-018-0118-9',
'volume': '17',
'author': 'Cui',
'year': '2019',
'journal-title': 'Nat Rev Microbiol'},
{ 'key': 'ref3',
'doi-asserted-by': 'publisher',
'first-page': '782',
'DOI': '10.1001/jama.2020.12839',
'volume': '324',
'author': 'Wiersinga',
'year': '2020',
'journal-title': 'JAMA'},
{ 'key': 'ref4',
'doi-asserted-by': 'publisher',
'first-page': '1100',
'DOI': '10.1016/j.it.2020.10.004',
'volume': '41',
'author': 'Harrison',
'year': '2020',
'journal-title': 'Trends Immunol'},
{ 'key': 'ref5',
'doi-asserted-by': 'publisher',
'first-page': '549',
'DOI': '10.1152/physiolgenomics.00089.2020',
'volume': '52',
'author': 'Pollard',
'year': '2020',
'journal-title': 'Physiol Genomics'},
{ 'key': 'ref6',
'doi-asserted-by': 'publisher',
'first-page': '22035',
'DOI': '10.1073/pnas.2006392117',
'volume': '117',
'author': 'Goldstein',
'year': '2020',
'journal-title': 'Proc Natl Acad Sci U S A'},
{ 'key': 'ref7',
'doi-asserted-by': 'publisher',
'first-page': '867',
'DOI': '10.1007/s40618-020-01236-2',
'volume': '43',
'author': 'Fadini',
'year': '2020',
'journal-title': 'J Endocrinol Invest'},
{ 'key': 'ref8',
'doi-asserted-by': 'publisher',
'first-page': '24',
'DOI': '10.1016/j.pcd.2020.08.015',
'volume': '15',
'author': 'Varikasuvu',
'year': '2021',
'journal-title': 'Prim Care Diabetes'},
{ 'key': 'ref9',
'doi-asserted-by': 'publisher',
'first-page': '11',
'author': 'Sun',
'year': '2021',
'journal-title': 'Front Pharmacol',
'DOI': '10.3389/fphar.2020.592439'},
{ 'key': 'ref10',
'doi-asserted-by': 'publisher',
'first-page': '201',
'DOI': '10.1016/j.amjms.2015.11.011',
'volume': '351',
'author': 'Jafar',
'year': '2016',
'journal-title': 'Am J Med Sci'},
{ 'key': 'ref11',
'doi-asserted-by': 'publisher',
'first-page': '2177',
'DOI': '10.1016/j.dsx.2020.11.006',
'volume': '14',
'author': 'Lukito',
'year': '2020',
'journal-title': 'Diabetes Metab Syndr'},
{ 'key': 'ref12',
'doi-asserted-by': 'publisher',
'first-page': '2999',
'DOI': '10.2337/dc20-1521',
'volume': '43',
'author': 'Solerte',
'year': '2020',
'journal-title': 'Dia Care'},
{ 'key': 'ref13',
'doi-asserted-by': 'publisher',
'first-page': '1946',
'DOI': '10.1111/dom.14097',
'volume': '22',
'author': 'Fadini',
'year': '2020',
'journal-title': 'Diabetes Obes Metab'},
{ 'key': 'ref14',
'doi-asserted-by': 'publisher',
'first-page': '1480',
'DOI': '10.1007/s00125-021-05458-8',
'volume': '64',
'author': 'Schlesinger',
'year': '2021',
'journal-title': 'Diabetologia'},
{ 'key': 'ref15',
'doi-asserted-by': 'publisher',
'first-page': '2612',
'DOI': '10.1016/j.numecd.2021.06.010',
'volume': '31',
'author': 'Bonora',
'year': '2021',
'journal-title': 'Nutr Metab Cardiovasc Dis'},
{ 'key': 'ref16',
'doi-asserted-by': 'publisher',
'first-page': '2054',
'DOI': '10.1038/s41591-021-01618-w',
'volume': '27',
'author': 'Webster',
'year': '2021',
'journal-title': 'Nat Med'},
{ 'key': 'ref17',
'doi-asserted-by': 'publisher',
'first-page': '535',
'DOI': '10.1016/j.dsx.2020.04.044',
'volume': '14',
'author': 'Kumar',
'year': '2020',
'journal-title': 'Diabetes Metab Syndr'},
{ 'key': 'ref18',
'doi-asserted-by': 'publisher',
'first-page': '65',
'DOI': '10.1016/j.cmet.2020.11.014',
'volume': '33',
'author': 'Yu',
'year': '2021',
'journal-title': 'Cell Metab'},
{ 'key': 'ref19',
'doi-asserted-by': 'publisher',
'first-page': '2223',
'DOI': '10.1007/s13300-021-01110-1',
'volume': '12',
'author': 'Boye',
'year': '2021',
'journal-title': 'Diabetes Ther'},
{ 'key': 'ref20',
'doi-asserted-by': 'publisher',
'first-page': '293',
'DOI': '10.1016/S2213-8587(21)00050-4',
'volume': '9',
'author': 'Khunti',
'year': '2021',
'journal-title': 'Lancet Diabetes Endocrinol'},
{ 'key': 'ref21',
'doi-asserted-by': 'publisher',
'first-page': '599',
'DOI': '10.1056/NEJMoa2201662',
'volume': '387',
'author': 'Bramante',
'year': '2022',
'journal-title': 'N Engl J Med'},
{ 'key': 'ref22',
'doi-asserted-by': 'publisher',
'first-page': '1040',
'DOI': '10.1016/j.annonc.2020.04.479',
'volume': '31',
'author': 'Montopoli',
'year': '2020',
'journal-title': 'Ann Oncol'}],
'container-title': 'Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://www.dovepress.com/getfile.php?fileID=84551',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://www.dovepress.com/getfile.php?fileID=84551',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2022, 10, 10]],
'date-time': '2022-10-10T05:55:12Z',
'timestamp': 1665381312000},
'score': 1,
'resource': { 'primary': { 'URL': 'https://www.dovepress.com/infection-rates-and-impact-of-glucose-lowering-medications-on-the-clin-peer-reviewed-fulltext-article-DMSO'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2022, 10]]},
'references-count': 22,
'URL': 'http://dx.doi.org/10.2147/DMSO.S385646',
'relation': {},
'ISSN': ['1178-7007'],
'subject': ['Pharmacology', 'Internal Medicine'],
'container-title-short': 'DMSO',
'published': {'date-parts': [[2022, 10]]}}
