Canagliflozin in Conjunction With Sulfonylurea Maintains Glycemic Control and Weight Loss Over 52 Weeks: A Randomized, Controlled Trial in Patients With Type 2 Diabetes Mellitus.

PURPOSE: Our aim was to investigate the long-term efficacy and safety of canagliflozin, a sodium-glucose co-transporter 2 inhibitor, added to background sulfonylurea (SU) monotherapy for patients with type 2 diabetes mellitus. METHODS: The CANagliflozin cardioVascularAssessment Study (CANVAS) was a double-blind, placebo-controlled cardiovascular outcomes study that randomly assigned participants to receive placebo or canagliflozin 100 or 300 mg once daily in addition to routine therapy. CANVAS included a prespecified SU substudy of patients taking background doses of SU monotherapy; data from the primary efficacy evaluation at 18 weeks have been published previously. We performed a retrospective analysis of the SU substudy at 52 weeks to measure long-term efficacy and safety of canagliflozin used with an SU. The primary objective of the long-term extension was to assess the change from baseline to 52 weeks in glycosylated hemoglobin (HbA1c). FINDINGS: A total of 215 patients were included in the 52-week extension study. Patients receiving both 100-mg and 300-mg doses of canagliflozin achieved a sustained reduction in HbA1c relative to patients receiving placebo (-0.61% [95% CI, -0.941% to -0.282%] and -0.66% [95% CI, -0.993% to -0.332%], respectively), regardless of baseline HbA1c, duration of diabetes, SU dose, estimated glomerular filtration rate, or body mass index. A sustained reduction in fasting plasma glucose was also found in both 100-mg and 300-mg groups, relative to the placebo group (-2.04 mmol/L [95% CI, -2.778 to -1.299 mmol/L] and -1.88 mmol/L [95% CI, -2.623 to -1.146 mmol/L], respectively). Weight was reduced significantly at 52 weeks in both 100-mg and 300-mg groups, relative to placebo (-1.9% [95% CI, -3.2% to -0.7%] and -2.0% [95% CI, -3.2% to -0.7%], respectively). Reduction in systolic blood pressure was also reported for both dose groups relative to the placebo group, but there was no clear difference in HDL-C, LDL-C, or triglyceride levels. Canagliflozin was generally well tolerated. While documented hypoglycemia occurred in 14% of patients on placebo, the frequency of hypoglycemia with the addition of canagliflozin was similar. There was an increased frequency of genital mycotic infections in both men (5.1%) and women (10.4%) in both canagliflozin groups combined, relative to the placebo group (0%), and their frequency increased in the higher-dose group. There was a slightly higher rate of renal impairment in those treated with canagliflozin versus placebo (2.1% vs 0%). IMPLICATIONS: After 52 weeks, patients receiving canagliflozin added to background SU had sustained reductions in HbA1c and fasting plasma glucose, without increasing hypoglycemia and body weight; safety findings were generally consistent with the known safety profile of the drug. ClinicalTrials.gov identifier: NCT01032629.

Giant cell aortitis: clinical presentation and outcomes in 40 patients consecutively operated on.

OBJECTIVES: Giant cell arteritis (GCA) may affect mid-size and large-size arteries. Although temporal arteritis is a well-characterized clinical entity, GCA of the thoracic aorta remains ill defined. The aim of the study was to evaluate the clinical presentation, surgical and mid-term outcomes in patients operated for GCA of the thoracic aorta. METHODS: A retrospective review of patients operated for GCA of the thoracic aorta was conducted. The diagnosis of GCA was established by the pathology report. RESULTS: Forty consecutive patients (mean age of 66.6 ± 9.1 years) with a diagnosis of GCA of the thoracic aorta were operated on. A history of polymyalgia rheumatica or temporal arteritis was positive in 22.5% of patients. Emergency surgery was performed in 10% of patients (3 'type A' dissections and 1 'type B'). Mega-aorta syndrome was present in 10% of patients. Involvement of the ascending aorta was present in 100% of patients. One patient had a previous branched thoracic endovascular replacement (TEVAR) with a type I proximal endoleak. In 4 patients, the thoracic aorta was totally replaced. Eighty-five percent of patients had an arch replacement; 79.4% a hemiarch and 20.6% a full arch. The mean circulatory arrest time was 16.3 ± 12.3 min. Eighty percent of patients had an aortic valve procedure; aortic valve replacement was performed in 50% of them and Bentall-De Bono/valve sparing in 50%. Cerebrovascular accident occurred in 2.5% of patients. No patient died during hospitalization. The mean hospital stay was 8.7 ± 3.0 days. The mean postoperative follow-up time was 4.2 ± 2.3 years, with a mean of 4.2 ± 2.2 thoraco-abdominal computed tomographies (CTs)/patient. Four patients had late reinterventions: 2 were valve-related, 1 for a distal type I endoleak treated with a distal TEVAR extension and 1 type II open thoraco-abdominal replacement for disease progression. One distal type I TEVAR endoleak was treated medically. Aortic diameter progressions on CT (mm/year) were 0.7 ± 1.0 mm for the arch, 1.2 ± 2.0 mm for the isthmus, 1.1 ± 1.7 mm for the mid-descending, 0.7 ± 0.9 mm for the aortic hiatus, 0.5 ± 0.5 mm for the supra-renal aorta and 0.6 ± 0.6 mm for the infra-renal aorta. One patient who declined reoperation on the descending aorta died suddenly 3 years after her initial operation. The 5-year overall survival rate was 91%. CONCLUSIONS: GCA of the thoracic aorta may be suspected in less than 25% of patients preoperatively. Clinical presentation may be acute or chronic with localized or diffused aortic involvement but always involved the ascending aorta. Surgery may be performed with excellent outcomes. Follow-up imaging is mandatory to assess aortic progression.