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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

Mirani et al., Diabetes Care, doi:10.2337/dc20-1340
Oct 2020  
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Mortality 45% Improvement Relative Risk Metformin for COVID-19  Mirani et al.  Prophylaxis Is prophylaxis with metformin beneficial for COVID-19? Retrospective 90 patients in Italy (February - April 2020) Lower mortality with metformin (not stat. sig., p=0.097) c19early.org Mirani et al., Diabetes Care, October 2020 Favorsmetformin Favorscontrol 0 0.5 1 1.5 2+
Metformin for COVID-19
3rd treatment shown to reduce risk in July 2020
 
*, now with p < 0.00000000001 from 91 studies.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,300+ studies for 75 treatments. c19early.org
Retrospective 90 hospitalized COVID-19 patients with diabetes in Italy, showing lower mortality with metformin use, without statistical significance.
risk of death, 45.0% lower, HR 0.55, p = 0.10, treatment 25 of 69 (36.2%), control 13 of 21 (61.9%), NNT 3.9, adjusted per study, Cox proportional hazards.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Mirani et al., 6 Oct 2020, retrospective, Italy, peer-reviewed, median age 66.0, 8 authors, study period 20 February, 2020 - 9 April, 2020. Contact: mirani@humanitas.it.
This PaperMetforminAll
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
Marco Mirani, Giuseppe Favacchio, Flaminia Carrone, Nazarena Betella, Emilia Biamonte, Emanuela Morenghi, Gherardo Mazziotti, Andrea Gerardo Lania
doi:10.2337/figshare.12980015.
Diabetes may unfavorably influence the outcome of coronavirus disease 19 , but the determinants of this effect are still poorly understood. In this monocentric study, we aimed at evaluating the impact of type 2 diabetes, comorbidities, plasma glucose levels, and antidiabetes medications on the survival of COVID-19 patients. RESEARCH DESIGN AND METHODS This was a case series involving 387 COVID-19 patients admitted to a single center in the region of Lombardy, the epicenter of the severe acute respiratory syndrome coronavirus 2 pandemic in Italy, between 20 February and 9 April 2020. Medical history, pharmacological treatments, laboratory findings, and clinical outcomes of patients without diabetes and patients with type 2 diabetes were compared. Cox proportional hazards analysis was applied to investigate risk factors associated with mortality. RESULTS Our samples included 90 patients (23.3%) with type 2 diabetes, who displayed double the mortality rate of subjects without diabetes (42.3% vs. 21.7%, P < 0.001). In spite of this, after correction for age and sex, risk of mortality was significantly associated with a history of hypertension (adjusted hazard ratio [aHR] 1.84, 95% CI 1.15-2.95; P 5 0.011), coronary artery disease (aHR 1.56, 95% CI 1.04-2.35; P 5 0.031), chronic kidney disease (aHR 2.07, 95% CI 1.27-3.38; P 5 0.003), stroke (aHR 2.09, 95% CI 1.23-3.55; P 5 0.006), and cancer (aHR 1.57, 95% CI 1.08-2.42; P 5 0.04) but not with type 2 diabetes (P 5 0.170). In patients with diabetes, elevated plasma glucose (aHR 1.22, 95% CI 1.04-1.44, per mmol/L; P 5 0.015) and IL-6 levels at admission (aHR 2.47, 95% CI 1.28-4.78, per 1-SD increase; P 5 0.007) as well as treatment with insulin (aHR 3.05, 95% CI 1.57-5.95; P 5 0.001) and b-blockers (aHR 3.20, 95% CI 1.50-6.60; P 5 0.001) were independently associated with increased mortality, whereas the use of dipeptidyl peptidase 4 inhibitors was significantly and independently associated with a lower risk of mortality (aHR 0.13, 95% CI 0.02-0.92; P 5 0.042). CONCLUSIONS Plasma glucose levels at admission and antidiabetes drugs may influence the survival of COVID-19 patients affected by type 2 diabetes.
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{ 'indexed': {'date-parts': [[2023, 8, 30]], 'date-time': '2023-08-30T14:40:47Z', 'timestamp': 1693406447588}, 'reference-count': 42, 'publisher': 'American Diabetes Association', 'issue': '12', 'license': [ { 'start': { 'date-parts': [[2020, 11, 20]], 'date-time': '2020-11-20T00:00:00Z', 'timestamp': 1605830400000}, 'content-version': 'vor', 'delay-in-days': 45, 'URL': 'https://www.diabetesjournals.org/content/license'}], 'content-domain': {'domain': ['diabetesjournals.org'], 'crossmark-restriction': True}, 'published-print': {'date-parts': [[2020, 12, 1]]}, 'abstract': '<jats:sec>\n' ' <jats:title>OBJECTIVE</jats:title>\n' ' <jats:p>Diabetes may unfavorably influence the outcome of coronavirus ' 'disease 19 (COVID-19), but the determinants of this effect are still poorly understood. In ' 'this monocentric study, we aimed at evaluating the impact of type 2 diabetes, comorbidities, ' 'plasma glucose levels, and antidiabetes medications on the survival of COVID-19 ' 'patients.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>RESEARCH DESIGN AND METHODS</jats:title>\n' ' <jats:p>This was a case series involving 387 COVID-19 patients admitted to ' 'a single center in the region of Lombardy, the epicenter of the severe acute respiratory ' 'syndrome coronavirus 2 pandemic in Italy, between 20 February and 9 April 2020. Medical ' 'history, pharmacological treatments, laboratory findings, and clinical outcomes of patients ' 'without diabetes and patients with type 2 diabetes were compared. Cox proportional hazards ' 'analysis was applied to investigate risk factors associated with mortality.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>RESULTS</jats:title>\n' ' <jats:p>Our samples included 90 patients (23.3%) with type 2 diabetes, who ' 'displayed double the mortality rate of subjects without diabetes (42.3% vs. 21.7%, P &amp;lt; ' '0.001). In spite of this, after correction for age and sex, risk of mortality was ' 'significantly associated with a history of hypertension (adjusted hazard ratio [aHR] 1.84, ' '95% CI 1.15–2.95; P = 0.011), coronary artery disease (aHR 1.56, 95% CI 1.04–2.35; P = ' '0.031), chronic kidney disease (aHR 2.07, 95% CI 1.27–3.38; P = 0.003), stroke (aHR 2.09, 95% ' 'CI 1.23–3.55; P = 0.006), and cancer (aHR 1.57, 95% CI 1.08–2.42; P = 0.04) but not with type ' '2 diabetes (P = 0.170). In patients with diabetes, elevated plasma glucose (aHR 1.22, 95% CI ' '1.04–1.44, per mmol/L; P = 0.015) and IL-6 levels at admission (aHR 2.47, 95% CI 1.28–4.78, ' 'per 1-SD increase; P = 0.007) as well as treatment with insulin (aHR 3.05, 95% CI 1.57–5.95; ' 'P = 0.001) and β-blockers (aHR 3.20, 95% CI 1.50–6.60; P = 0.001) were independently ' 'associated with increased mortality, whereas the use of dipeptidyl peptidase 4 inhibitors was ' 'significantly and independently associated with a lower risk of mortality (aHR 0.13, 95% CI ' '0.02–0.92; P = 0.042).</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>CONCLUSIONS</jats:title>\n' ' <jats:p>Plasma glucose levels at admission and antidiabetes drugs may ' 'influence the survival of COVID-19 patients affected by type 2 diabetes.</jats:p>\n' ' </jats:sec>', 'DOI': '10.2337/dc20-1340', 'type': 'journal-article', 'created': {'date-parts': [[2020, 10, 7]], 'date-time': '2020-10-07T04:00:11Z', 'timestamp': 1602043211000}, 'page': '3042-3049', 'update-policy': 'http://dx.doi.org/10.2337/ada-journal-policies', 'source': 'Crossref', 'is-referenced-by-count': 106, 'title': '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', 'prefix': '10.2337', 'volume': '43', 'author': [ { 'given': 'Marco', 'family': 'Mirani', 'sequence': 'first', 'affiliation': [ { 'name': 'Endocrinology and Diabetology Unit, Humanitas Clinical and ' 'Research Center, IRCCS, Milan, Italy'}]}, { 'ORCID': 'http://orcid.org/0000-0002-4187-5378', 'authenticated-orcid': False, 'given': 'Giuseppe', 'family': 'Favacchio', 'sequence': 'additional', 'affiliation': [ { 'name': 'Endocrinology and Diabetology Unit, Humanitas Clinical and ' 'Research Center, IRCCS, Milan, Italy'}]}, { 'given': 'Flaminia', 'family': 'Carrone', 'sequence': 'additional', 'affiliation': [ { 'name': 'Endocrinology and Diabetology Unit, Humanitas Clinical and ' 'Research Center, IRCCS, Milan, Italy'}]}, { 'given': 'Nazarena', 'family': 'Betella', 'sequence': 'additional', 'affiliation': [ { 'name': 'Endocrinology and Diabetology Unit, Humanitas Clinical and ' 'Research Center, IRCCS, Milan, Italy'}]}, { 'given': 'Emilia', 'family': 'Biamonte', 'sequence': 'additional', 'affiliation': [ { 'name': 'Endocrinology and Diabetology Unit, Humanitas Clinical and ' 'Research Center, IRCCS, Milan, Italy'}]}, { 'given': 'Emanuela', 'family': 'Morenghi', 'sequence': 'additional', 'affiliation': [ { 'name': 'Biostatistics Unit, Humanitas Clinical and Research Center, ' 'IRCCS, Milan, Italy'}]}, { 'given': 'Gherardo', 'family': 'Mazziotti', 'sequence': 'additional', 'affiliation': [ { 'name': 'Endocrinology and Diabetology Unit, Humanitas Clinical and ' 'Research Center, IRCCS, Milan, Italy'}, { 'name': 'Department of Biomedical Sciences, Humanitas University, Milan, ' 'Italy'}]}, { 'given': 'Andrea Gerardo', 'family': 'Lania', 'sequence': 'additional', 'affiliation': [ { 'name': 'Endocrinology and Diabetology Unit, Humanitas Clinical and ' 'Research Center, IRCCS, Milan, Italy'}, { 'name': 'Department of Biomedical Sciences, Humanitas University, Milan, ' 'Italy'}]}], 'member': '1167', 'published-online': {'date-parts': [[2020, 10, 6]]}, 'reference': [ { 'key': '2022031220332739900_B1', 'doi-asserted-by': 'crossref', 'first-page': '507', 'DOI': '10.1016/S0140-6736(20)30211-7', 'article-title': 'Epidemiological and clinical characteristics of 99 cases of 2019 novel ' 'coronavirus pneumonia in Wuhan, China: a descriptive study', 'volume': '395', 'author': 'Chen', 'year': '2020', 'journal-title': 'Lancet'}, { 'key': '2022031220332739900_B2', 'unstructured': 'World Health Organization\n' " . 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Edition 2.0, 13 ' 'March 2020', 'volume-title': 'Infez Med', 'author': 'Lombardy Section Italian Society Infectious And Tropical Diseases', 'year': '2020'}, { 'key': '2022031220332739900_B26', 'doi-asserted-by': 'crossref', 'first-page': '249', 'DOI': '10.1007/s00592-018-1222-z', 'article-title': 'The efficacy and safety of dipeptidyl peptidase-4 inhibitors for type 2 ' 'diabetes: a Bayesian network meta-analysis of 58 randomized controlled ' 'trials', 'volume': '56', 'author': 'Ling', 'year': '2019', 'journal-title': 'Acta Diabetol'}, { 'key': '2022031220332739900_B27', 'article-title': 'Impact of diabetes on COVID-19-related in-hospital mortality: a ' 'retrospective study from Northern Italy', 'author': 'Ciardullo', 'journal-title': 'J Endocrinol Invest'}, { 'key': '2022031220332739900_B28', 'doi-asserted-by': 'crossref', 'first-page': '366', 'DOI': '10.1161/HYPERTENSIONAHA.120.15324', 'article-title': 'Age and multimorbidity predict death among COVID-19 patients: results ' 'of the SARS-RAS study of the Italian Society of Hypertension', 'volume': '76', 'author': 'Iaccarino', 'year': '2020', 'journal-title': 'Hypertension'}, { 'key': '2022031220332739900_B29', 'doi-asserted-by': 'crossref', 'first-page': 'e2012270', 'DOI': '10.1001/jamanetworkopen.2020.12270', 'article-title': 'Clinical characteristics and morbidity associated with coronavirus ' 'disease 2019 in a series of patients in metropolitan Detroit', 'volume': '3', 'author': 'Suleyman', 'year': '2020', 'journal-title': 'JAMA Netw Open'}, { 'key': '2022031220332739900_B30', 'first-page': '2052', 'article-title': 'Presenting characteristics, comorbidities, and outcomes among 5700 ' 'patients hospitalized with COVID-19 in the New York City area ' '[published correction appears in JAMA 2020;323:2098]', 'volume-title': 'JAMA', 'author': 'Richardson', 'year': '2020'}, { 'key': '2022031220332739900_B31', 'article-title': 'The relationship between diabetes and clinical outcomes in COVID-19: a ' 'single-center retrospective analysis', 'author': 'Fox', 'journal-title': 'Acta Diabetol'}, { 'key': '2022031220332739900_B32', 'doi-asserted-by': 'crossref', 'first-page': '2345', 'DOI': '10.2337/dc20-1380', 'article-title': 'Hyperglycemia at hospital admission is associated with severity of the ' 'prognosis in patients hospitalized for COVID-19: the Pisa COVID-19 ' 'Study', 'volume': '43', 'author': 'Coppelli', 'year': '2020', 'journal-title': 'Diabetes Care'}, { 'key': '2022031220332739900_B33', 'doi-asserted-by': 'crossref', 'first-page': '276', 'DOI': '10.1097/SHK.0000000000000778', 'article-title': 'Diabetes mellitus and sepsis: a challenging association', 'volume': '47', 'author': 'Trevelin', 'year': '2017', 'journal-title': 'Shock'}, { 'key': '2022031220332739900_B34', 'doi-asserted-by': 'crossref', 'first-page': '588', 'DOI': '10.1097/MCC.0000000000000153', 'article-title': 'Sepsis-induced acute kidney injury revisited: pathophysiology, ' 'prevention and future therapies', 'volume': '20', 'author': 'Zarbock', 'year': '2014', 'journal-title': 'Curr Opin Crit Care'}, { 'key': '2022031220332739900_B35', 'doi-asserted-by': 'crossref', 'first-page': '1582', 'DOI': '10.3389/fimmu.2020.01582', 'article-title': 'The effects of type 2 diabetes mellitus on organ metabolism and the ' 'immune system', 'volume': '11', 'author': 'Daryabor', 'year': '2020', 'journal-title': 'Front Immunol'}, { 'key': '2022031220332739900_B36', 'doi-asserted-by': 'crossref', 'first-page': '934', 'DOI': '10.1001/jamainternmed.2020.0994', 'article-title': 'Risk factors associated with acute respiratory distress syndrome and ' 'death in patients with coronavirus disease 2019 pneumonia in Wuhan, ' 'China', 'volume': '180', 'author': 'Wu', 'year': '2020', 'journal-title': 'JAMA Intern Med'}, { 'key': '2022031220332739900_B37', 'doi-asserted-by': 'crossref', 'first-page': '420', 'DOI': '10.1016/S2213-2600(20)30076-X', 'article-title': 'Pathological findings of COVID-19 associated with acute respiratory ' 'distress syndrome', 'volume': '8', 'author': 'Xu', 'year': '2020', 'journal-title': 'Lancet Respir Med'}, { 'key': '2022031220332739900_B38', 'doi-asserted-by': 'crossref', 'first-page': 'S98', 'DOI': '10.2337/dc20-S009', 'article-title': '9. Pharmacologic approaches to glycemic treatment: Standards of Medical ' 'Care in Diabetes—2020', 'volume': '43', 'author': 'American Diabetes Association', 'year': '2020', 'journal-title': 'Diabetes Care'}, { 'key': '2022031220332739900_B39', 'doi-asserted-by': 'crossref', 'first-page': '601', 'DOI': '10.1080/22221751.2020.1739565', 'article-title': 'Emerging WuHan (COVID-19) coronavirus: glycan shield and structure ' 'prediction of spike glycoprotein and its interaction with human CD26', 'volume': '9', 'author': 'Vankadari', 'year': '2020', 'journal-title': 'Emerg Microbes Infect'}, { 'key': '2022031220332739900_B40', 'doi-asserted-by': 'crossref', 'first-page': '1444', 'DOI': '10.1126/science.abb2762', 'article-title': 'Structural basis for the recognition of SARS-CoV-2 by full-length human ' 'ACE2', 'volume': '367', 'author': 'Yan', 'year': '2020', 'journal-title': 'Science'}, { 'key': '2022031220332739900_B41', 'doi-asserted-by': 'crossref', 'first-page': '108125', 'DOI': '10.1016/j.diabres.2020.108125', 'article-title': 'COVID-19 and diabetes: can DPP4 inhibition play a role', 'volume': '162', 'author': 'Iacobellis', 'year': '2020', 'journal-title': 'Diabetes Res Clin Pract'}, { 'key': '2022031220332739900_B42', 'doi-asserted-by': 'crossref', 'first-page': '108216', 'DOI': '10.1016/j.diabres.2020.108216', 'article-title': 'Is DPP4 inhibition a comrade or adversary in COVID-19 infection', 'volume': '164', 'author': 'Dalan', 'year': '2020', 'journal-title': 'Diabetes Res Clin Pract'}], 'container-title': 'Diabetes Care', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://diabetesjournals.org/care/article-pdf/43/12/3042/530950/dc201340.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'syndication'}, { 'URL': 'https://diabetesjournals.org/care/article-pdf/43/12/3042/530950/dc201340.pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 3, 12]], 'date-time': '2022-03-12T22:37:56Z', 'timestamp': 1647124676000}, 'score': 1, 'resource': { 'primary': { 'URL': 'https://diabetesjournals.org/care/article/43/12/3042/30894/Impact-of-Comorbidities-and-Glycemia-at-Admission'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2020, 10, 6]]}, 'references-count': 42, 'journal-issue': { 'issue': '12', 'published-online': {'date-parts': [[2020, 10, 6]]}, 'published-print': {'date-parts': [[2020, 12, 1]]}}, 'URL': 'http://dx.doi.org/10.2337/dc20-1340', 'relation': {}, 'ISSN': ['0149-5992', '1935-5548'], 'subject': [ 'Advanced and Specialized Nursing', 'Endocrinology, Diabetes and Metabolism', 'Internal Medicine'], 'published': {'date-parts': [[2020, 10, 6]]}}
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Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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