{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T23:57:16Z","timestamp":1788479836110,"version":"build-2803163510"},"reference-count":42,"publisher":"American Diabetes Association","issue":"3","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"vor","delay-in-days":226,"URL":"http:\/\/www.diabetesjournals.org\/site\/license"}],"funder":[{"DOI":"10.13039\/100005205","name":"Janssen Research & Development, LLC","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Janssen Global Services, LLC"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,3,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>This study assessed the efficacy\/safety of canagliflozin (CANA), a sodium\u2013glucose cotransporter 2 (SGLT2) inhibitor, plus metformin extended-release (MET) initial therapy in drug-na\u00efve type 2 diabetes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>This 26-week, double-blind, phase 3 study randomized 1,186 patients to CANA 100 mg (CANA100)\/MET, CANA 300 mg (CANA300)\/MET, CANA100, CANA300, or MET. Primary end point was change in HbA1c at week 26 for combinations versus monotherapies. Secondary end points included noninferiority in HbA1c lowering with CANA monotherapy versus MET; changes in fasting plasma glucose, body weight, and blood pressure; and proportion of patients achieving HbA1c &amp;lt;7.0% (&amp;lt;53 mmol\/mol).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>From mean baseline HbA1c of 8.8% (73 mmol\/mol), CANA100\/MET and CANA300\/MET significantly lowered HbA1c versus MET (median dose, 2,000 mg\/day) by \u20131.77%, \u20131.78%, and \u20131.30% (\u201319.3, \u201319.5, and \u201314.2 mmol\/mol; differences of \u22120.46% and \u20130.48% [\u20135.0 and \u20135.2 mmol\/mol]; P = 0.001) and versus CANA100 and CANA300 by \u20131.37% and \u20131.42% (\u201315.0 and \u201315.5 mmol\/mol; differences of \u20130.40% and \u20130.36% [\u20134.4 and \u20133.9 mmol\/mol]; P = 0.001). CANA100 and CANA300 monotherapy met noninferiority for HbA1c lowering and had significantly more weight loss versus MET (\u20132.8, \u20133.7, and \u20131.9 kg [\u20133.0%, \u20133.9%, and \u20132.1%]; P = 0.016 and P = 0.002). Greater attainment of HbA1c &amp;lt;7.0% (50%, 57%, and 43%) and significantly more weight loss (\u20133.2, \u20133.9, and \u20131.9 kg [\u20133.5%, \u20134.2%, and \u20132.1%]; P = 0.001) occurred with CANA100\/MET and CANA300\/MET versus MET. The incidence of adverse events (AEs) related to SGLT2 inhibition (genital mycotic infections, osmotic diuresis\u2013 and volume depletion\u2013related AEs) was higher in the CANA arms (0.4\u20134.4%) versus MET (0\u20130.8%). AE-related discontinuation rates were 1.3\u20133.0% across groups. The incidence of hypoglycemia was 3.0\u20135.5% in the CANA arms and 4.6% with MET.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Initial therapy with CANA plus MET was more effective and generally well tolerated versus each monotherapy in drug-na\u00efve type 2 diabetes. CANA monotherapy demonstrated noninferior HbA1c lowering versus MET.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc15-1736","type":"journal-article","created":{"date-parts":[[2016,1,20]],"date-time":"2016-01-20T03:38:08Z","timestamp":1453261088000},"page":"353-362","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":123,"title":["Initial Combination Therapy With Canagliflozin Plus Metformin Versus Each Component as Monotherapy for Drug-Na\u00efve Type 2 Diabetes"],"prefix":"10.2337","volume":"39","author":[{"given":"Julio","family":"Rosenstock","sequence":"first","affiliation":[{"name":"Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard","family":"Chuck","sequence":"additional","affiliation":[{"name":"Diablo Clinical Research, Walnut Creek, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Gonz\u00e1lez-Ortiz","sequence":"additional","affiliation":[{"name":"Institute of Experimental and Clinical Therapeutics, Physiology Department, Health Science University Center, University of Guadalajara, Guadalajara, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Merton","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC, Raritan, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagriti","family":"Craig","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC, Raritan, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Capuano","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC, Raritan, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Qiu","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC, Raritan, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2016,1,19]]},"reference":[{"key":"2022031301070207700_B1","doi-asserted-by":"crossref","first-page":"140","DOI":"10.2337\/dc14-2441","article-title":"Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes","volume":"38","author":"Inzucchi","year":"2015","journal-title":"Diabetes Care"},{"key":"2022031301070207700_B2","first-page":"S1","volume":"38","author":"American Diabetes Association","year":"2015","journal-title":"Diabetes Care"},{"key":"2022031301070207700_B3","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/S0140-6736(98)07019-6","article-title":"Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)","volume":"352","author":"UK Prospective Diabetes Study (UKPDS) Group","year":"1998","journal-title":"Lancet"},{"key":"2022031301070207700_B4","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1136\/bmj.321.7258.405","article-title":"Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study","volume":"321","author":"Stratton","year":"2000","journal-title":"BMJ"},{"key":"2022031301070207700_B5","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1503\/cmaj.1031414","article-title":"Oral antihyperglycemic therapy for type 2 diabetes mellitus","volume":"172","author":"Cheng","year":"2005","journal-title":"CMAJ"},{"key":"2022031301070207700_B6","doi-asserted-by":"crossref","first-page":"429","DOI":"10.4093\/dmj.2013.37.6.429","article-title":"Metformin based dual-combination therapies in drug na\u00efve type 2 diabetic patients","volume":"37","author":"Kim","year":"2013","journal-title":"Diabetes Metab J"},{"key":"2022031301070207700_B7","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.1016\/j.amjmed.2010.11.003","article-title":"Initial combination therapy for type 2 diabetes mellitus: is it ready for prime time","volume":"124","author":"Zinman","year":"2011","journal-title":"Am J Med"},{"key":"2022031301070207700_B8","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.jcjd.2013.01.009","article-title":"Canadian Diabetes Association 2013 clinical practice guidelines for the prevention and management of diabetes in Canada. 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