{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:41:11Z","timestamp":1791268871706,"version":"4.1.0"},"reference-count":31,"publisher":"American Diabetes Association","issue":"3","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,3,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>There are limited data about the effects of sodium\u2013glucose cotransporter 2 inhibitors when used with insulin. We report the efficacy and safety of canagliflozin in patients with type 2 diabetes using insulin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>The CANagliflozin CardioVascular Assessment Study is a double-blind, placebo-controlled study that randomized participants to placebo, canagliflozin 100 mg, or canagliflozin 300 mg once daily, added to a range of therapies. The primary end point of this substudy was the change in HbA1c from baseline at 18 weeks among patients using insulin; 52-week effects were also examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Individuals receiving insulin at baseline were randomized to receive placebo (n = 690), canagliflozin 100 mg (n = 692), or canagliflozin 300 mg (n = 690). These individuals were 66% male and had a median age of 63 years, mean HbA1c of 8.3% (67 mmol\/mol), BMI of 33.1 kg\/m2, estimated glomerular filtration rate of 75 mL\/min\/1.73 m2, fasting plasma glucose of 9.2 mmol\/L, and a median daily insulin dose of 60 IU. Most individuals were using basal\/bolus insulin. Reductions in HbA1c with canagliflozin 100 and 300 mg versus placebo were \u22120.62% (95% CI \u22120.69, \u22120.54; \u22126.8 mmol\/mol [95% CI \u22127.5, \u22125.9]; P &amp;lt; 0.001) and \u22120.73% (95% CI \u22120.81, \u22120.65; \u22128.0 mmol\/mol [95% CI \u22128.9, \u22127.1]; P &amp;lt; 0.001) at 18 weeks and \u22120.58% (95% CI \u22120.68, \u22120.48; \u22126.3 mmol\/mol [95% CI \u22127.4, \u22125.2]) and \u22120.73% (95% CI \u22120.83, \u22120.63; \u22128.0 mmol\/mol [95% CI \u22129.1, \u22126.9]) at 52 weeks. There were significant falls in fasting plasma glucose, body weight, and blood pressure at both time points and there was a greater incidence of hypoglycemia, genital mycotic infections, and hypovolemia with both canagliflozin doses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>Canagliflozin added to insulin therapy improved glycemic control and decreased body weight. There was a greater frequency of several anticipated side effects, although few led to discontinuation of treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/dc14-1237","type":"journal-article","created":{"date-parts":[[2014,12,3]],"date-time":"2014-12-03T01:11:43Z","timestamp":1417569103000},"page":"403-411","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":196,"title":["Efficacy and Safety of Canagliflozin, an Inhibitor of Sodium\u2013Glucose Cotransporter 2, When Used in Conjunction With Insulin Therapy in Patients With Type 2 Diabetes"],"prefix":"10.2337","volume":"38","author":[{"given":"Bruce","family":"Neal","sequence":"first","affiliation":[{"name":"The George Institute for Global Health, The University of Sydney and the Royal Prince Alfred Hospital, Sydney, 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Canagliflozin as an adjunctive treatment to diet and exercise alone or coadministered with other antihyperglycemic agents to improve glycemic control in adults with type 2 diabetes mellitus. JNJ-28431754 (Canagliflozin). NDA 204042 [Internet], 2013. Available from http:\/\/www.fda.gov\/downloads\/advisorycommittees\/committeesmeetingmaterials\/drugs\/endocrinologicandmetabolicdrugsadvisorycommittee\/ucm334551.pdf. 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