Background: Few prospective studies have compared the cardiovascular benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors. We aimed to clarify the efficacy of dapagliflozin versus sitagliptin for modulating cardiometabolic risk factors including high glycated hemoglobin (HbA1c) levels, hypoglycemia, and body weight. Methods: This prospective, randomized, open-label, blinded-endpoint, parallel-group trial enrolled 340 Japanese patients with early-stage type 2 diabetes receiving metformin alone or no glucose-lowering agents, who were randomized to receive dapagliflozin or sitagliptin for 24 weeks. The primary endpoint was the proportion of patients who achieved the composite endpoint of HbA1c level maintenance < 7.0% (53 mmol/mol), avoidance of hypoglycemia (maintenance of sensor glucose ≥ 3.0 mmol/L or ≥ 54 mg/dL), and ≥ 3.0% body weight loss from baseline. Secondary endpoints included components of the primary endpoint, other metabolic indices, and glucose variability indices measured using flash glucose monitoring. Results: Clinical characteristics of patients were age, 58.1 ± 12.2 years; known duration of diabetes, 5.8 ± 6.1 years; body weight, 74.7 ± 14.2 kg; body mass index, 27.9 ± 4.1 kg/m 2 ; and HbA1c level, 7.8 ± 0.8% at baseline. The achievement ratio of primary endpoint was significantly higher in the dapagliflozin group than in the sitagliptin group (24.4% vs. 13.8%, P < 0.05). While the rates of HbA1c level maintenance < 7.0% (53 mmol/mol) and avoidance of hypoglycemia were comparable between the groups (49.4 vs. 50.0% and 88.7 vs. 92.3% for dapagliflozin vs. sitagliptin, respectively), body weight loss of ≥ 3.0% was significantly achieved in the dapagliflozin group (54.4 vs. 19.6%, P < 0.001). Moreover, dapagliflozin was superior to sitagliptin regarding several secondary endpoints that modulate cardiometabolic risk, namely reducing fasting plasma glucose, insulin, uric acid, increasing high-density lipoprotein cholesterol, and suppressing the increase in serum creatinine and the decrease in estimated glomerular filtration rate. On the other hand, sitagliptin was superior to dapagliflozin in suppressing glucose variability.

Nivolumab has promising efficacy for treating various advanced malignant tumors, although it has been reported to induce a wide range of autoimmune adverse effects. We herein report the case of a patient with metastatic lung adenocarcinoma who developed adrenal insufficiency after 12 cycles of nivolumab treatment. Endocrine test results supported a diagnosis of isolated adrenocorticotropic hormone deficiency due to hypophysitis, and replacement therapy using hydrocortisone has been successful. Although hypophysitis is a rare immune-related adverse event that is associated with nivolumab therapy, clinical awareness is essential, as this condition can be life-threatening and requires prompt treatment.

BackgroundRecent studies reported that sodium glucose cotransporter 2 (SGLT2) inhibitors reduced the cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus (T2DM) compared to placebo in contrast to no reduction with dipeptidyl peptidase 4 (DPP4) inhibitors. However, there are no comparative studies on the effects of SGLT2 inhibitors and DPP4 inhibitors on HbA1c, body weight and hypoglycemia as risk factors of cardiovascular diseases. The aim of the present ongoing study is to compare the effects of dapagliflozin, a SGLT2 inhibitor, with those of sitagliptin, a DPP4 inhibitor, on cardiovascular risk factors in T2DM patients with inadequate glycemic control.MethodsThe study of dapagliflozin versus sitagliptin treatment efficacy on prevention of cardiovascular risk factors in T2DM patients (DIVERSITY-CVR study) is a prospective, randomized, open-label, blinded-endpoint, parallel-group, comparative study. A total of 340 T2DM patients treated with metformin alone or with no glucose-lowering agents (hemoglobin A1c ≥ 7.0 and < 10.0%) will be randomized into the dapagliflozin group (5–10 mg/day, n = 170) and the sitagliptin group (50–100 mg/day, n = 170), and treated for 24 weeks. The primary endpoint is the rate of achieving a composite endpoint of the following three items at 24th week; (1) HbA1c < 7.0%; (2) body weight loss of ≥ 3.0% from baseline; (3) avoidance of hypoglycemia. Hypoglycemia will be monitored using the flash glucose monitoring system. The secondary outcomes include each component of the primary endpoint, plus indices of lipid metabolism, and evaluations related to safety.ConclusionsThere is lack of solid information on differences in the therapeutic effects of SGLT2 inhibitors and DPP4 inhibitors on multiple risk factors for cardiovascular diseases. It is anticipated that the results of the DIVERSITY-CVR study provides useful clinical data on the management of patients with T2DM, including reducing the risk of CVD. The results of this study will become available in 2019.Trial registration University Hospital Medical Information Network Clinical Trial Registry (UMIN000028014). Registered 30 June 2017Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0730-z) contains supplementary material, which is available to authorized users.

Background: Sodium glucose cotransporter 2 inhibitors (SGLT2i) have attracted attention by the recently reported improved cardiovascular (CV) outcomes in patients with T2DM. In contrast, dipeptidyl peptidase 4 inhibitors (DPP-4i) were reported neutral on CV outcomes. However, there are few prospective studies that have compared the efficacy of SGLT2i and DPP-4i on the prevention of CV disease risks. Therefore, we planned this prospective, randomized, parallel-group trial aimed to compare the therapeutic benefits of dapagliflozin (Dapa) and sitagliptin (Sita) on CV disease risks, with special focus on HbA1c, body weight (BW), and hypoglycemia. Methods: A total of 340 T2DM patients treated with metformin alone or with no glucose-lowering agents (20-80 years of age, HbA1c ≥ 7.1% and &lt; 10.0%) were equally randomized to Dapa 5 mg/day or Sita 50 mg/day add-on group, and treated for 24 weeks. After the 8 weeks, if HbA1c is 7.0% or higher, Dapa and Sita were increased to 10 mg/day and 100 mg/day, respectively. The primary endpoint was the ratio of achieving composite endpoints of the following all 3 items; 1) HbA1c below 7.0%; 2) 3.0% BW loss from baseline; 3) avoidance of hypoglycemia {&lt; 3.0 mmol/L (&lt; 54 mg/dL)}. Hypoglycemia was monitored by flash glucose monitoring system. Results: The achievement ratio of HbA1c below 7.0% was comparable between the groups (49.4 vs. 50.0%, p=1.00, Dapa vs. Sita, respectively). However, 3.0% BW loss was preferably achieved in Dapa group (54.4 vs. 19.6%, p&lt;0.001). There was no significant difference regarding the avoidance of hypoglycemia between the groups (88.7 vs. 92.3%, p=0.27). Thus, the ratio of achieving composite endpoints was superior in Dapa group compared to Sita group (24.4% vs. 13.8%, p&lt;0.05). In summary, Dapa treatment for 24 weeks improved CV risk factors in patients with inadequately controlled T2DM. This study provides the evidence on ideal therapeutic choice for preventing CV events in T2DM. Disclosure A. Fuchigami: None. F. Shigiyama: None. T. Kitazawa: Speaker’s Bureau; Self; AstraZeneca, Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. Y. Okada: None. T. Ichijo: None. M. Higa: None. T. Hiyoshi: Other Relationship; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly Japan K.K., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. I. Inoue: None. K. Iso: Research Support; Spouse/Partner; AstraZeneca. H. Yoshii: None. T. Hirose: None. N. Kumashiro: Speaker’s Bureau; Self; Novo Nordisk Inc., Sanofi, Takeda Pharmaceutical Company Limited. Funding AstraZeneca K.K.

It is well known the primary aldosteronism (PA) is most common endocrinological hypertension and accounted for 10% among all hypertension population, and it develops cardiovascular disease more frequently than blood pressure matched essential hypertension. Many literatures have been reported patients with obesity often shows hyperaldosteronism by hyperactivation of sympathetic nerves, over secretion from adipocytes themselves, or aldosterone-secreting factors from adipocytes. Thus, we investigated the impact of BMI on diagnosis of PA in this study. We investigated 328 cases of adrenal venous sampling performed patients with PA in our hospital since 2007, including 125 males and 203 females, and their mean age was 56.1 ± 11.8 years old. We evaluated the relationship of those patients’ body mass index (BMI) with gender, systolic and diastolic blood pressure (SBP and DBP, respectively), serum sodium, serum potassium, plasma renin activity (PRA), plasma aldosterone concentration (PAC), aldosterone-renin ratio (ARR), ACTH, cortisol, and the ratio of patients who showed 1 mg dexamethasone suppression test positive, and none of each showed statistical relationship with BMI. In confirmatory tests, we evaluated those values of PRA at 120 min. in upright furosemide test, either higher values of ARR at 60min. or 90 min. in captopril challenge test, and PAC at 4 hours in saline infusion test (SIT), also positive ratio of those test considered by PRA <2.0 ng/ml/hr, ARR >20, and PAC>6.0 in those tests, respectively. In adrenal venous sampling (AVS), we evaluated lateralized ratio (LR) and contralateral ratio (CR) and those positive ratios considered by LR >4 or CR<1. In our results, only positive ratio of SIT in the confirmatory tests and CR in AVS showed positive relationship with BMI. The ratio of unilateral hyperaldosteronism considered by LR>4 and CR<1 also showed no relationship. Then, we evaluated all consideration above only among 304 patients with bilateral hyperaldosteronism by AVS, suspicious of idiopathic hyperaldosteronism (IHA), because it was reported patients with obesity and hyperaldosteronism are more commonly diagnosed as IHA. Although, all evaluation showed same results. In conclusion, our result revealed the relationship of BMI with positive ratio of SIT and CR, and this means obesity, at least, could affect the diagnosis of PA. We must be very careful to make diagnosis of PA, especially in patients with obesity.