{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T16:12:10Z","timestamp":1789229530861,"version":"build-2803163510"},"reference-count":40,"publisher":"American Diabetes Association","issue":"3","license":[{"start":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T00:00:00Z","timestamp":1613692800000},"content-version":"vor","delay-in-days":8,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["K08AG055670"],"award-info":[{"award-number":["K08AG055670"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,3,1]]},"abstract":"<jats:sec><jats:title>OBJECTIVE<\/jats:title><jats:p>Both sodium\u2013glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) demonstrated cardiovascular benefits in randomized controlled trials of patients with type 2 diabetes (T2D) generally &amp;lt;65 years old and mostly with cardiovascular disease. We aimed to evaluate the comparative effectiveness and safety of SGLT2i and GLP-1RA among real-world older adults.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESEARCH DESIGN AND METHODS<\/jats:title><jats:p>Using Medicare data (April 2013\u2013December 2016), we identified 90,094 propensity score\u2013matched (1:1) T2D patients \u226566 years old initiating SGLT2i or GLP-1RA. Primary outcomes were major adverse cardiovascular events (MACE) (i.e., myocardial infarction, stroke, or cardiovascular death) and hospitalization for heart failure (HHF). Other outcomes included diabetic ketoacidosis (DKA), genital infections, fractures, lower-limb amputations (LLA), acute kidney injury (AKI), severe urinary tract infections, and overall mortality. We estimated hazard ratios (HRs) and rate differences (RDs) per 1,000 person-years, controlling for 140 baseline covariates.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Compared with GLP-1RA, SGLT2i initiators had similar MACE risk (HR 0.98 [95% CI 0.87, 1.10]; RD \u22120.38 [95% CI \u22122.48, 1.72]) and reduced HHF risk (HR 0.68 [95% CI 0.57, 0.80]; RD \u22123.23 [95% CI \u22124.68, \u22121.77]), over a median follow-up of \u223c6 months. They also had 0.7 more DKA events (RD 0.72 [95% CI 0.02, 1.41]), 0.9 more LLA (RD 0.90 [95% CI 0.10, 1.70]), 57.1 more genital infections (RD 57.08 [95% CI 53.45, 60.70]), and 7.1 fewer AKI events (RD \u22127.05 [95% CI \u221210.27, \u22123.83]) per 1,000 person-years.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Among older adults, those taking SGLT2i had similar MACE risk, decreased HHF risk, and increased risk of DKA, LLA, and genital infections versus those taking GLP-1RA.<\/jats:p><\/jats:sec>","DOI":"10.2337\/dc20-1464","type":"journal-article","created":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T20:45:37Z","timestamp":1611607537000},"page":"826-835","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":107,"title":["Comparative Effectiveness and Safety of Sodium\u2013Glucose Cotransporter 2 Inhibitors Versus Glucagon-Like Peptide 1 Receptor Agonists in Older Adults"],"prefix":"10.2337","volume":"44","author":[{"given":"Elisabetta","family":"Patorno","sequence":"first","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8809-9898","authenticated-orcid":false,"given":"Ajinkya","family":"Pawar","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily G.","family":"Bessette","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae H.","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA"},{"name":"Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA"},{"name":"Division of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chintan","family":"Dave","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA"},{"name":"Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7160-9345","authenticated-orcid":false,"given":"Robert J.","family":"Glynn","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Medha N.","family":"Munshi","sequence":"additional","affiliation":[{"name":"Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA"},{"name":"Joslin Diabetes Center, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6917-4197","authenticated-orcid":false,"given":"Sebastian","family":"Schneeweiss","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J.","family":"Wexler","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Diabetes Center and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seoyoung C.","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2021,2,11]]},"reference":[{"key":"2022031309373429900_B1","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.2337\/dc12-1801","article-title":"Diabetes in older adults","volume":"35","author":"Kirkman","year":"2012","journal-title":"Diabetes Care"},{"key":"2022031309373429900_B2","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.2337\/dc06-1136","article-title":"Impact of recent increase in incidence on future diabetes burden: U.S., 2005-2050","volume":"29","author":"Narayan","year":"2006","journal-title":"Diabetes Care"},{"key":"2022031309373429900_B3","doi-asserted-by":"crossref","first-page":"487","DOI":"10.2337\/dci19-0066","article-title":"2019 update to: management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)","volume":"43","author":"Buse","year":"2020","journal-title":"Diabetes Care"},{"key":"2022031309373429900_B4","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1056\/NEJMoa1603827","article-title":"Liraglutide and cardiovascular outcomes in type 2 diabetes","volume":"375","author":"Marso","year":"2016","journal-title":"N Engl J Med"},{"key":"2022031309373429900_B5","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1056\/NEJMoa1607141","article-title":"Semaglutide and cardiovascular outcomes in patients with type 2 diabetes","volume":"375","author":"Marso","year":"2016","journal-title":"N Engl J Med"},{"key":"2022031309373429900_B6","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1016\/S0140-6736(18)32261-X","article-title":"Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial","volume":"392","author":"Hernandez","year":"2018","journal-title":"Lancet"},{"key":"2022031309373429900_B7","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0140-6736(19)31149-3","article-title":"Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial","volume":"394","author":"Gerstein","year":"2019","journal-title":"Lancet"},{"key":"2022031309373429900_B8","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1056\/NEJMoa1504720","article-title":"Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes","volume":"373","author":"Zinman","year":"2015","journal-title":"N Engl J Med"},{"key":"2022031309373429900_B9","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1056\/NEJMoa1611925","article-title":"Canagliflozin and cardiovascular and renal events in type 2 diabetes","volume":"377","author":"Neal","year":"2017","journal-title":"N Engl J Med"},{"key":"2022031309373429900_B10","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1056\/NEJMoa1612917","article-title":"Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes","volume":"377","author":"Holman","year":"2017","journal-title":"N Engl J Med"},{"key":"2022031309373429900_B11","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1056\/NEJMoa1812389","article-title":"Dapagliflozin and cardiovascular outcomes in type 2 diabetes","volume":"380","author":"Wiviott","year":"2019","journal-title":"N Engl J Med"},{"key":"2022031309373429900_B12","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1056\/NEJMoa1515920","article-title":"Empagliflozin and progression of kidney disease in type 2 diabetes","volume":"375","author":"Wanner","year":"2016","journal-title":"N Engl J Med"},{"key":"2022031309373429900_B13","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1056\/NEJMoa1811744","article-title":"Canagliflozin and renal outcomes in type 2 diabetes and nephropathy","volume":"380","author":"Perkovic","year":"2019","journal-title":"N Engl J Med"},{"key":"2022031309373429900_B14","unstructured":"U.S. Food and Drug Administration . FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections, 2015. Accessed 15 June 2020. Available from https:\/\/www.fda.gov\/drugs\/drug-safety-and-availability\/fda-drug-safety-communication-fda-revises-labels-sglt2-inhibitors-diabetes-include-warnings-about"},{"key":"2022031309373429900_B15","unstructured":"U.S. Food and Drug Administration . FDA revises label of diabetes drug canagliflozin (Invokana, Invokamet) to include updates on bone fracture risk and new information on decreased bone mineral density, 2015. Accessed 15 June 2020. Available from https:\/\/www.fda.gov\/drugs\/drug-safety-and-availability\/fda-drug-safety-communication-fda-revises-label-diabetes-drug-canagliflozin-invokana-invokamet"},{"key":"2022031309373429900_B16","unstructured":"U.S. Food and Drug Administration . FDA confirms increased risk of leg and foot amputations with the diabetes medicine canagliflozin (Invokana, Invokamet, Invokamet XR), 2017. Accessed 15 June 2020. Available from https:\/\/www.fda.gov\/media\/104870\/download"},{"key":"2022031309373429900_B17","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ahj.2004.02.013","article-title":"Accuracy of Medicare claims-based diagnosis of acute myocardial infarction: estimating positive predictive value on the basis of review of hospital records","volume":"148","author":"Kiyota","year":"2004","journal-title":"Am Heart J"},{"key":"2022031309373429900_B18","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1002\/pds.1924","article-title":"Validation of claims-based diagnostic and procedure codes for cardiovascular and gastrointestinal serious adverse events in a commercially-insured population","volume":"19","author":"Wahl","year":"2010","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"2022031309373429900_B19","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1161\/01.STR.0000032240.28636.BD","article-title":"Validating administrative data in stroke research","volume":"33","author":"Tirschwell","year":"2002","journal-title":"Stroke"},{"key":"2022031309373429900_B20","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/pds.2313","article-title":"A systematic review of validated methods for identifying heart failure using administrative data","volume":"21","author":"Saczynski","year":"2012","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"2022031309373429900_B21","doi-asserted-by":"crossref","first-page":"e004966","DOI":"10.1161\/JAHA.116.004966","article-title":"Comparison of expert adjudicated coronary heart disease and cardiovascular disease mortality with the national death index: results from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study","volume":"6","author":"Olubowale","year":"2017","journal-title":"J Am Heart Assoc"},{"key":"2022031309373429900_B22","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/1471-2288-11-157","article-title":"Positive predictive value of automated database records for diabetic ketoacidosis (DKA) in children and youth exposed to antipsychotic drugs or control medications: a Tennessee Medicaid Study","volume":"11","author":"Bobo","year":"2011","journal-title":"BMC Med Res Methodol"},{"key":"2022031309373429900_B23","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0895-4356(98)00161-9","article-title":"The use of automated data to identify complications and comorbidities of diabetes: a validation study","volume":"52","author":"Newton","year":"1999","journal-title":"J Clin Epidemiol"},{"key":"2022031309373429900_B24","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/0895-4356(92)90047-Q","article-title":"Identification of fractures from computerized Medicare files","volume":"45","author":"Ray","year":"1992","journal-title":"J Clin Epidemiol"},{"key":"2022031309373429900_B25","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.jclinepi.2012.10.004","article-title":"The validity of administrative data to identify hip fractures is high--a systematic review","volume":"66","author":"Hudson","year":"2013","journal-title":"J Clin Epidemiol"},{"key":"2022031309373429900_B26","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1681\/ASN.2006010073","article-title":"Validity of International Classification of Diseases, Ninth Revision, Clinical Modification codes for acute renal failure","volume":"17","author":"Waikar","year":"2006","journal-title":"J Am Soc Nephrol"},{"key":"2022031309373429900_B27","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1111\/dom.13531","article-title":"Comparative risk of genital infections associated with sodium-glucose co-transporter-2 inhibitors","volume":"21","author":"Dave","year":"2019","journal-title":"Diabetes Obes Metab"},{"key":"2022031309373429900_B28","doi-asserted-by":"crossref","first-page":"248","DOI":"10.7326\/M18-3136","article-title":"Sodium-glucose cotransporter-2 inhibitors and the risk for severe urinary tract infections: a population-based cohort study","volume":"171","author":"Dave","year":"2019","journal-title":"Ann Intern Med"},{"key":"2022031309373429900_B29","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1093\/gerona\/glx229","article-title":"Measuring frailty in Medicare data: development and validation of a claims-based frailty index","volume":"73","author":"Kim","year":"2018","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"2022031309373429900_B30","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.1002\/sim.3697","article-title":"Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples","volume":"28","author":"Austin","year":"2009","journal-title":"Stat Med"},{"key":"2022031309373429900_B31","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/cpt.329","article-title":"Transparency and reproducibility of observational cohort studies using large healthcare databases","volume":"99","author":"Wang","year":"2016","journal-title":"Clin Pharmacol Ther"},{"key":"2022031309373429900_B32","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.jclinepi.2010.10.004","article-title":"A combined comorbidity score predicted mortality in elderly patients better than existing scores","volume":"64","author":"Gagne","year":"2011","journal-title":"J Clin Epidemiol"},{"key":"2022031309373429900_B33","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1161\/CIRCULATIONAHA.118.038868","article-title":"Comparison of the effects of glucagon-like peptide receptor agonists and sodium-glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular and renal outcomes in type 2 diabetes mellitus","volume":"139","author":"Zelniker","year":"2019","journal-title":"Circulation"},{"key":"2022031309373429900_B34","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(18)32590-X","article-title":"SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials","volume":"393","author":"Zelniker","year":"2019","journal-title":"Lancet"},{"key":"2022031309373429900_B35","doi-asserted-by":"crossref","first-page":"k4365","DOI":"10.1136\/bmj.k4365","article-title":"Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study","volume":"363","author":"Ueda","year":"2018","journal-title":"BMJ"},{"key":"2022031309373429900_B36","doi-asserted-by":"crossref","first-page":"155","DOI":"10.7326\/M18-0567","article-title":"Fracture risk after initiation of use of canagliflozin: a cohort study","volume":"170","author":"Fralick","year":"2019","journal-title":"Ann Intern Med"},{"key":"2022031309373429900_B37","doi-asserted-by":"crossref","first-page":"m2812","DOI":"10.1136\/bmj.m2812","article-title":"Risk of amputation with canagliflozin across categories of age and cardiovascular risk in three US nationwide databases: cohort study","volume":"370","author":"Fralick","year":"2020","journal-title":"BMJ"},{"key":"2022031309373429900_B38","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.2337\/dc20-0267","article-title":"Sodium-glucose cotransporter 2 inhibitors and the risk of below-knee amputation: a multicenter observational study","volume":"43","author":"Yu","year":"2020","journal-title":"Diabetes Care"},{"key":"2022031309373429900_B39","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1111\/dom.13184","article-title":"Claims-based studies of oral glucose-lowering medications can achieve balance in critical clinical variables only observed in electronic health records","volume":"20","author":"Patorno","year":"2018","journal-title":"Diabetes Obes Metab"},{"key":"2022031309373429900_B40","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1111\/dom.12926","article-title":"Safety issues with glucagon-like peptide-1 receptor agonists (pancreatitis, pancreatic cancer and cholelithiasis): data from randomized controlled trials","volume":"19","author":"Monami","year":"2017","journal-title":"Diabetes Obes Metab"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/care.diabetesjournals.org\/syndication\/doi\/10.2337\/dc20-1464","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/44\/3\/826\/632093\/dc201464.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/44\/3\/826\/632093\/dc201464.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T04:03:41Z","timestamp":1697688221000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/44\/3\/826\/138588\/Comparative-Effectiveness-and-Safety-of-Sodium"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,11]]},"references-count":40,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,2,11]]},"published-print":{"date-parts":[[2021,3,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc20-1464","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,11]]}}}