Abstract
OBJECTIVE To determine the respective associations of premorbid glucagon-like peptide-1 receptor agonist (GLP1-RA) and sodium–glucose cotransporter 2 inhibitor (SGLT2i) use, compared with premorbid dipeptidyl peptidase 4 inhibitor (DPP4i) use, with severity of outcomes in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RESEARCH DESIGN AND METHODS We analyzed observational data from SARS-CoV-2–positive adults in the National COVID Cohort Collaborative (N3C), a multicenter, longitudinal U.S. cohort (January 2018–February 2021), with a prescription for GLP1-RA, SGLT2i, or DPP4i within 24 months of positive SARS-CoV-2 PCR test. The primary outcome was 60day mortality, measured from positive SARS-CoV-2 test date. Secondary outcomes were total mortality during the observation period and emergency room visits, hospitalization, and mechanical ventilation within 14 days. Associations were quantified with odds ratios (ORs) estimated with targeted maximum likelihood estimation using a super learner approach, accounting for baseline characteristics. RESULTS The study included 12,446 individuals (53.4% female, 62.5% White, mean ± SD age 58.6 ± 13.1 years). The 60-day mortality was 3.11% (387 of 12,446), with 2.06% (138 of 6,692) for GLP1-RA use, 2.32% (85 of 3,665) for SGLT2i use, and 5.67% (199 of 3,511) for DPP4i use. Both GLP1-RA and SGLT2i use were associated with lower 60-day mortality compared with DPP4i use (OR 0.54 [95% CI 0.37–0.80] and 0.66 [0.50–0.86], respectively). Use of both medications was also associated with decreased total mortality, emergency room visits, and hospitalizations. CONCLUSIONS Among SARS-CoV-2–positive adults, premorbid GLP1-RA and SGLT2i use, compared with DPP4i use, was associated with lower odds of mortality and other adverse outcomes, although DPP4i users were older and generally sicker.
Original language | English (US) |
---|---|
Pages (from-to) | 1564-1572 |
Number of pages | 9 |
Journal | Diabetes care |
Volume | 44 |
Issue number | 7 |
DOIs | |
State | Published - 2021 |
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
- Advanced and Specialized Nursing
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Association between glucagonlike peptide 1 receptor agonist and sodium–glucose cotransporter 2 inhibitor use and covid-19 outcomes. / Kahkoska, Anna R.; Abrahamsen, Trine Julie; Alexander, G. Caleb et al.
In: Diabetes care, Vol. 44, No. 7, 2021, p. 1564-1572.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Association between glucagonlike peptide 1 receptor agonist and sodium–glucose cotransporter 2 inhibitor use and covid-19 outcomes
AU - Kahkoska, Anna R.
AU - Abrahamsen, Trine Julie
AU - Alexander, G. Caleb
AU - Bennett, Tellen D.
AU - Chute, Christopher G.
AU - Haendel, Melissa A.
AU - Klein, Klara R.
AU - Mehta, Hemalkumar
AU - Miller, Joshua D.
AU - Moffitt, Richard A.
AU - Stüurmer, Til
AU - Kvist, Kajsa
AU - Buse, John B.
N1 - Funding Information: National Institutes of Health and the Patient-Centered Outcomes Research Institute. This work was supported, in part, by NCATS UL1 TR002535 and NCATS UL1 TR002535 03S2. The analyses described here were conducted with data or tools accessed through the NCATS N3C Data Enclave (https:// covid.cd2h.org) and supported by NCATS U24 TR002306. N3C is supported by the following grant sources: Carilion Clinic (UL1TR003015-02S2: Provision of Clinical Data to Support a Nationwide COVID-19 Cohort Collaborative), George Washington Children's Research Institute (UL1TR001876: Clinical and Translational Science Institute at Children's National), Duke University (UL1TR002553: Duke Clinical and Translational Science Award), Johns Hopkins University (UL1TR003098: Johns Hopkins Institute for Clinical and Translational Research), Mayo Clinic Rochester (UL1TR002377: Mayo Clinic Center for Clinical and Translational Science), Medical University of South Carolina (UL1TR001450: South Carolina Clinical & Translational Research Institute), Penn State Health Milton S. Hershey Medical Center (UL1TR002014: Penn State Clinical and Translational Science Institute), Rush University Medical Center (UL1TR002389: Institute for Translational Medicine), Stony Brook University (U24TR002306-04S1), The Ohio State University (UL1TR002733: The OSU Center for Clinical and Translational Science: Advancing Today's Discoveries to Improve Health), Tufts University (Boston, MA) (UL1TR002544-03S4: Tufts Clinical and Translational Science Institute N3C Supplement), University of Massachusetts Medical School (Worcester, MA) (UL1TR001453: University of Massachusetts Center for Clinical and Translational Science), University of Alabama at Birmingham (UL1TR003096: Center for Clinical and Translational Science), University of Arkansas for Medical Sciences (UL1TR003107: UAMS Translational Research Institute), The University of Chicago (UL1TR002389: ITM 2.0: Advancing Translational Science in Metropolitan Chicago), University of Colorado Denver (UL1TR002535-03S2: Colorado Clinical and Translational Sciences Institute Participation in the National COVID Cohort Collaborative N3C), University of Illinois at Chicago (UL1TR002003: Clinical and Translational Science Award), The University of Iowa (UL1TR002537: The University of Iowa Clinical and Translational Science Award), University of Kentucky (UL1TR001998-04S1: Kentucky Center for Clinical and Translational Science), Maine Medical Center (P20GM103423), University of Miami (UL1TR002736: Miami Clinical and Translational Science Institute), The University of Michigan at Ann Arbor (UL1TR002240: Michigan Institute for Clinical and Health Research), University of Minnesota (UL1TR002494: University of Minnesota Clinical and Translational Science Institute), University of Nebraska–Lincoln (U54GM115458: University of Nebraska Center for Clinical & Translational Research), University of North Carolina at Chapel Hill (UL1TR002489: NC Translational and Clinical Sciences Institute and the ICEES1 COVID-19 Open Infrastructure to Democratize and Accelerate Cross-Institutional Clinical Data Sharing and Research), Northwestern University (UL1TR001422), University of Southern California (UL1TR001855: Southern California Clinical and Translational Institute), The University of Texas Medical Branch at Galveston (UL1TR001439: UTMB Clinical and Translational Science Award), The University of Utah (UL1TR002538-03S3: Infrastructure Support for Participation in the N3C Data Repository), University of Washington (UL1TR002319: Institute of Translational Health Sciences), University of Wisconsin-Madison (UL1TR002373: Institutional Clinical and Translational Science Award), University of Virginia (UL1TR003015-02S2: Provision of Clinical Data to Support a Nationwide COVID-19 Cohort Collaborative), Virginia Commonwealth University (UL1TR002649-03S3: N3C & All of Us Research Program Collaborative Project), Wake Forest University Health Sciences (UL1TR001420: Wake Forest Clinical and Translational Science Award), Washington University in St. Louis (UL1TR002345: Washington University Institute of Clinical Translational Sciences), and West Virginia University (U54GM104942: West Virginia Clinical and Translational Science Institute). Duality of Interest. A.R.K. has received support from Novo Nordisk for travel to present data (June 2019). G.C.A. has served as a paid advisor to IQVIA; is a cofounding principal and equity holder in Monument Analytics, a health care consultancy whose clients include the life sciences industry as well as plaintiffs in opioid litigation; and is a member of OptumRx’s National P&T Committee. T.S. also receives salary support from the Center for Pharmacoepi-demiology (current members: GlaxoSmithKline, UCB BioSciences, Takeda, AbbVie, Boehringer Ingelheim); from Novo Nordisk and from a generous contribution by Dr. Nancy A. Dreyer (IQVIA, Chief Scientific Officer and Global Chief of Scientific Affairs) to the Department of Epidemiology, University of North Carolina at Chapel Hill. He owns stock in Novartis, Roche, and Novo Nordisk. J.B.B.’s contracted consulting fees and travel support for contracted activities are paid to the University of North Carolina at Chapel Hill by Adocia, AstraZeneca, Dance Bio-pharm, Dexcom, Eli Lilly, Fractyl, GI Dynamics, Intarcia Therapeutics, Lexicon, MannKind, Meta-vention, NovaTarg, Novo Nordisk, Orexigen, PhaseBio, Sanofi, Senseonics, vTv Therapeutics, and Zafgen; he reports grant support from AstraZeneca, Eli Lilly, Intarcia Therapeutics, Johnson & Johnson, Lexicon, Medtronic, Nova-Targ, Novo Nordisk, Sanofi, Theracos, Tolerion, and vTv Therapeutics; he is a consultant to Cirius Therapeutics, CSL Behring, Fortress Biotech, Mellitus Health, Moderna, Neurimmune AG, Pendulum Therapeutics, Praetego, Stability Health, and Zealand Pharma; and he holds stock/options in Mellitus Health, Pendulum Therapeutics, PhaseBio, and Stability Health. M.A.H. is a founder of Pryzm Health. No other potential conflicts of interest relevant to this article were reported. Funding Information: Acknowledgments. The authors are grateful for the vision of the National Center for Advancing Translational Science (NCATS) in supporting the development of N3C as a freely available resource, for the dozens of health care system leaders who generously agreed to participate in this audacious effort by sharing data, to the hundreds of people who enabled the data sharing, to the thousands of health care workers and their supporters who collected the data, and to the millions of patients and their families whose peril in this pandemic is reflected herein. This research was possible because of the patients whose information is included within the data and the organizations (see covid.cd2h.org) and scientists who have contributed to the ongoing development of this community resource (19). The authors thank Vibeke Kildegaard Knudsen, PhD, and Heidi Sørensen, PhD (Novo Nordisk A/S), for medical writing assistance. Funding. A.R.K. is supported by National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), under award F30DK113728. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. J.B.B.’s effort was supported by grants from the NCATS (UL1TR002489) and National Institute of Diabetes and Digestive and Kidney Diseases (P30DK124723), NIH. T.S. receives investigator-initiated research funding and support from the National Institute on Aging, NIH, as Principal Investigator (R01 AG056479) and as Co-Investigator (R01 HL118255, R01MD011680). T.D.B. receives research funding from NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development and NIH/NCATS. G.C.A. formerly served as Chair of the U.S. Food and Drug Administration’s Peripheral and Central Nervous System Advisory Committee. T.S. receives salary support as Director of Comparative Effectiveness Research (CER), NC TraCS Institute, and from UNC Clinical and Translational Science Award UL1TR002489. J.B. B. is supported by grants from the National Institutes of Health, American Diabetes Association, and the Patient-Centered Outcomes Research Institute. M.A.H. is supported by grants from the Funding Information: A.R.K. is supported by National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), under award F30DK113728. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. J.B.B.’s effort was supported by grants from the NCATS (UL1TR002489) and National Institute of Diabetes and Digestive and Kidney Diseases (P30DK124723), NIH. T.S. receives investigator-initiated research funding and support from the National Institute on Aging, NIH, as Principal Investigator (R01 AG056479) and as Co-Investigator (R01 HL118255, R01MD011680). T.D.B. receives research funding from NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development and NIH/NCATS. G.C.A. formerly served as Chair of the U.S. Food and Drug Administration’s Peripheral and Central Nervous System Advisory Committee. T.S. receives salary support as Director of Comparative Effectiveness Research (CER), NC TraCS Institute, and from UNC Clinical and Translational Science Award UL1TR002489. J.B. B. is supported by grants from the National Institutes of Health, American Diabetes Association, and the Patient-Centered Outcomes Research Institute. M.A.H. is supported by grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute. This work was supported, in part, by NCATS UL1 TR002535 and NCATS UL1 TR002535 03S2. The analyses described here were conducted with data or tools accessed through the NCATS N3C Data Enclave (https:// covid.cd2h.org) and supported by NCATS U24 TR002306. N3C is supported by the following grant sources: Carilion Clinic (UL1TR003015-02S2: Provision of Clinical Data to Support a Nationwide COVID-19 Cohort Collaborative), George Washington Children's Research Institute (UL1TR001876: Clinical and Translational Science Institute at Children's National), Duke University (UL1TR002553: Duke Clinical and Translational Science Award), Johns Hopkins University (UL1TR003098: Johns Hopkins Institute for Clinical and Translational Research), Mayo Clinic Rochester (UL1TR002377: Mayo Clinic Center for Clinical and Translational Science), Medical University of South Carolina (UL1TR001450: South Carolina Clinical & Translational Research Institute), Penn State Health Milton S. Hershey Medical Center (UL1TR002014: Penn State Clinical and Translational Science Institute), Rush University Medical Center (UL1TR002389: Institute for Translational Medicine), Stony Brook University (U24TR002306-04S1), The Ohio State University (UL1TR002733: The OSU Center for Clinical and Translational Science: Advancing Today's Discoveries to Improve Health), Tufts University (Boston, MA) (UL1TR002544-03S4: Tufts Clinical and Translational Science Institute N3C Supplement), University of Massachusetts Medical School (Worcester, MA) (UL1TR001453: University of Massachusetts Center for Clinical and Translational Science), University of Alabama at Birmingham (UL1TR003096: Center for Clinical and Translational Science), University of Arkansas for Medical Sciences (UL1TR003107: UAMS Translational Research Institute), The University of Chicago (UL1TR002389: ITM 2.0: Advancing Translational Science in Metropolitan Chicago), University of Colorado Denver (UL1TR002535-03S2: Colorado Clinical and Translational Sciences Institute Participation in the National COVID Cohort Collaborative N3C), University of Illinois at Chicago (UL1TR002003: Clinical and Translational Science Award), The University of Iowa (UL1TR002537: The University of Iowa Clinical and Translational Science Award), University of Kentucky (UL1TR001998-04S1: Kentucky Center for Clinical and Translational Science), Maine Medical Center (P20GM103423), University of Miami (UL1TR002736: Miami Clinical and Translational Science Institute), The University of Michigan at Ann Arbor (UL1TR002240: Michigan Institute for Clinical and Health Research), University of Minnesota (UL1TR002494: University of Minnesota Clinical and Translational Science Institute), University of Nebraska–Lincoln (U54GM115458: University of Nebraska Center for Clinical & Translational Research), University of North Carolina at Chapel Hill (UL1TR002489: NC Translational and Clinical Sciences Institute and the ICEES+ COVID-19 Open Infrastructure to Democratize and Accelerate Cross-Institutional Clinical Data Sharing and Research), Northwestern University (UL1TR001422), University of Southern California (UL1TR001855: Southern California Clinical and Translational Institute), The University of Texas Medical Branch at Galveston (UL1TR001439: UTMB Clinical and Translational Science Award), The University of Utah (UL1TR002538-03S3: Infrastructure Support for Participation in the N3C Data Repository), University of Washington (UL1TR002319: Institute of Translational Health Sciences), University of Wisconsin-Madison (UL1TR002373: Institutional Clinical and Translational Science Award), University of Virginia (UL1TR003015-02S2: Provision of Clinical Data to Support a Nationwide COVID-19 Cohort Collaborative), Virginia Commonwealth University (UL1TR002649-03S3: N3C & All of Us Research Program Collaborative Project), Wake Forest University Health Sciences (UL1TR001420: Wake Forest Clinical and Translational Science Award), Washington University in St. Louis (UL1TR002345: Washington University Institute of Clinical Translational Sciences), and West Virginia University (U54GM104942: West Virginia Clinical and Translational Science Institute). Duality of Interest. A.R.K. has received support from Novo Nordisk for travel to present data (June 2019). G.C.A. has served as a paid advisor to IQVIA; is a cofounding principal and equity holder in Monument Analytics, a health care consultancy whose clients include the life sciences industry as well as plaintiffs in opioid litigation; and is a member of OptumRx’s National P&T Committee. T.S. also receives salary support from the Center for Pharmacoepidemiology (current members: GlaxoSmithKline, UCB BioSciences, Takeda, AbbVie, Boehringer Ingelheim); from Novo Nordisk and from a generous contribution by Dr. Nancy A. Dreyer (IQVIA, Chief Scientific Officer and Global Chief of Scientific Affairs) to the Department of Epidemiology, University of North Carolina at Chapel Hill. He owns stock in Novartis, Roche, and Novo Nordisk. J.B.B.’s contracted consulting fees and travel support for contracted activities are paid to the University of North Carolina at Chapel Hill by Adocia, AstraZeneca, Dance Biopharm, Dexcom, Eli Lilly, Fractyl, GI Dynamics, Intarcia Therapeutics, Lexicon, MannKind, Metavention, NovaTarg, Novo Nordisk, Orexigen, PhaseBio, Sanofi, Senseonics, vTv Therapeutics, and Zafgen; he reports grant support from AstraZeneca, Eli Lilly, Intarcia Therapeutics, Johnson & Johnson, Lexicon, Medtronic, NovaTarg, Novo Nordisk, Sanofi, Theracos, Tolerion, and vTv Therapeutics; he is a consultant to Cirius Therapeutics, CSL Behring, Fortress Biotech, Mellitus Health, Moderna, Neurimmune AG, Pendulum Therapeutics, Praetego, Stability Health, and Zealand Pharma; and he holds stock/options in Mellitus Health, Pendulum Therapeutics, PhaseBio, and Stability Health. M.A.H. is a founder of Pryzm Health. No other potential conflicts of interest relevant to this article were reported. Publisher Copyright: © 2021 by the American Diabetes Association.
PY - 2021
Y1 - 2021
N2 - OBJECTIVE To determine the respective associations of premorbid glucagon-like peptide-1 receptor agonist (GLP1-RA) and sodium–glucose cotransporter 2 inhibitor (SGLT2i) use, compared with premorbid dipeptidyl peptidase 4 inhibitor (DPP4i) use, with severity of outcomes in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RESEARCH DESIGN AND METHODS We analyzed observational data from SARS-CoV-2–positive adults in the National COVID Cohort Collaborative (N3C), a multicenter, longitudinal U.S. cohort (January 2018–February 2021), with a prescription for GLP1-RA, SGLT2i, or DPP4i within 24 months of positive SARS-CoV-2 PCR test. The primary outcome was 60day mortality, measured from positive SARS-CoV-2 test date. Secondary outcomes were total mortality during the observation period and emergency room visits, hospitalization, and mechanical ventilation within 14 days. Associations were quantified with odds ratios (ORs) estimated with targeted maximum likelihood estimation using a super learner approach, accounting for baseline characteristics. RESULTS The study included 12,446 individuals (53.4% female, 62.5% White, mean ± SD age 58.6 ± 13.1 years). The 60-day mortality was 3.11% (387 of 12,446), with 2.06% (138 of 6,692) for GLP1-RA use, 2.32% (85 of 3,665) for SGLT2i use, and 5.67% (199 of 3,511) for DPP4i use. Both GLP1-RA and SGLT2i use were associated with lower 60-day mortality compared with DPP4i use (OR 0.54 [95% CI 0.37–0.80] and 0.66 [0.50–0.86], respectively). Use of both medications was also associated with decreased total mortality, emergency room visits, and hospitalizations. CONCLUSIONS Among SARS-CoV-2–positive adults, premorbid GLP1-RA and SGLT2i use, compared with DPP4i use, was associated with lower odds of mortality and other adverse outcomes, although DPP4i users were older and generally sicker.
AB - OBJECTIVE To determine the respective associations of premorbid glucagon-like peptide-1 receptor agonist (GLP1-RA) and sodium–glucose cotransporter 2 inhibitor (SGLT2i) use, compared with premorbid dipeptidyl peptidase 4 inhibitor (DPP4i) use, with severity of outcomes in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RESEARCH DESIGN AND METHODS We analyzed observational data from SARS-CoV-2–positive adults in the National COVID Cohort Collaborative (N3C), a multicenter, longitudinal U.S. cohort (January 2018–February 2021), with a prescription for GLP1-RA, SGLT2i, or DPP4i within 24 months of positive SARS-CoV-2 PCR test. The primary outcome was 60day mortality, measured from positive SARS-CoV-2 test date. Secondary outcomes were total mortality during the observation period and emergency room visits, hospitalization, and mechanical ventilation within 14 days. Associations were quantified with odds ratios (ORs) estimated with targeted maximum likelihood estimation using a super learner approach, accounting for baseline characteristics. RESULTS The study included 12,446 individuals (53.4% female, 62.5% White, mean ± SD age 58.6 ± 13.1 years). The 60-day mortality was 3.11% (387 of 12,446), with 2.06% (138 of 6,692) for GLP1-RA use, 2.32% (85 of 3,665) for SGLT2i use, and 5.67% (199 of 3,511) for DPP4i use. Both GLP1-RA and SGLT2i use were associated with lower 60-day mortality compared with DPP4i use (OR 0.54 [95% CI 0.37–0.80] and 0.66 [0.50–0.86], respectively). Use of both medications was also associated with decreased total mortality, emergency room visits, and hospitalizations. CONCLUSIONS Among SARS-CoV-2–positive adults, premorbid GLP1-RA and SGLT2i use, compared with DPP4i use, was associated with lower odds of mortality and other adverse outcomes, although DPP4i users were older and generally sicker.
UR - http://www.scopus.com/inward/record.url?scp=85114459486&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85114459486&partnerID=8YFLogxK
U2 - 10.2337/dc21-0065
DO - 10.2337/dc21-0065
M3 - Article
C2 - 34135013
AN - SCOPUS:85114459486
VL - 44
SP - 1564
EP - 1572
JO - Diabetes Care
JF - Diabetes Care
SN - 1935-5548
IS - 7
ER -