Efficacy and safety of bexagliflozin compared with dapagliflozin as an adjunct to metformin in Chinese patients with type 2 diabetes mellitus: A 24-week, randomized, double-blind, active-controlled, phase 3 trial.

BACKGROUND: Bexagliflozin and dapagliflozin are sodium-glucose cotransporter-2 (SGLT2) inhibitors. No direct comparison of SGLT2 inhibitors in a randomized controlled trial has been reported to date. METHODS: This was a multicenter, randomized, double-blind, active-controlled trial comparing bexagliflozin to dapagliflozin for the treatment of type 2 diabetes mellitus in adults with disease inadequately controlled by metformin. Subjects (n = 406) were randomized to receive bexagliflozin (20 mg) or dapagliflozin (10 mg) plus metformin. The primary endpoint was noninferiority of bexagliflozin to dapagliflozin for the change in glycated hemoglobin (HbA1c) from baseline to week 24. Secondary endpoints included intergroup differences in fasting plasma glucose (FPG), 2-h-postprandial glucose (PPG), body weight, and systolic blood pressure (SBP) from baseline to week 24. The trial also evaluated the safety profiles. RESULTS: The model-adjusted mean change from baseline to week 24 HbA1c was -1.08% for bexagliflozin and -1.10% for dapagliflozin. The intergroup difference of 0.03% (95% confidence interval [CI] -0.14% to 0.19%) was below the prespecified margin of 0.4%, confirming the noninferiority of bexagliflozin. The changes from baseline in FPG, PPG, body weight, and SBP were -1.95 mmol/L, -3.24 mmol/L, -2.52 kg, and -6.4 mm Hg in the bexagliflozin arm and -1.87 mmol/L, -3.07 mmol/L, -2.22 kg, and -6.3 mm Hg in the dapagliflozin arm. Adverse events were experienced in 62.6% and 65.0% and serious adverse events affected 4.4% and 3.5% of subjects in the bexagliflozin and dapagliflozin arm, respectively. CONCLUSIONS: Bexagliflozin showed nearly identical effects and a similar safety profile to dapagliflozin when used in Chinese patients on metformin.

Epidemiology and risk factors for diabetes in the suburbs of Beijing: a retrospective cohort study.

OBJECTIVE: We aimed to detect the incidence and risk factors of type 2 diabetes mellitus (T2DM) development in the suburbs of Beijing. DESIGN: Cohort study with record linkage to incidence data. SETTING: We performed a 5-year follow-up study in a randomly selected suburban population including 1114 subjects aged ≥18 years living in the suburbs of Beijing. PARTICIPANTS: 118 subjects with T2DM at baseline according to the 1999 WHO criteria were excluded, and 895 subjects attended the follow-up assessment in 2012. The non-diabetic subjects at baseline were classified into two groups: normal glucose tolerance (NGT) group (n=673) and impaired glucose regulation (IGR) group(n=222).The incidence and risk factors of diabetes development in each group were investigated. OUTCOME MEASURES: A structured questionnaire about sociodemographic characteristics, height, weight, waist circumference, hip circumference, blood pressure, oral glucose tolerance test and serum lipid levels. RESULTS: Out of the 895 non-diabetic subjects, 67 developed diabetes with 29 in the NGT group and 38 in the IGR group, respectively, after a 5-year follow-up, producing an overall 5-year cumulative incidence of diabetes of 13%. The incidence of diabetes was 15.5 cases per 1000 person-years, 8.9 cases per 1000 person-years in the NGT group and 35.7 cases per 1000 person-years in the IGR group (p<0.01; RR 4.03; 95% CI 2.58 to 9.29). Binary logistic regression analysis showed that the risk factors for diabetes development included fasting plasma glucose (FPG) in the NGT group, and sex, the waist-to-hip ratio, FPG and diastolic blood pressure (DBP) in the IGR group. CONCLUSIONS: During a mean follow-up of 5.0 years, the incidence of T2DM in the suburbs of Beijing was 15.5 per 1000 person-years. Early prevention of diabetes should focus on IGR subjects. Elevated FPG predicted diabetes development for both NGT and IGR subjects. Female sex, overweight/obesity and DBP are risk factors for diabetes development in IGR subjects.

Genotypic and phenotypic spectra of hemojuvelin mutations in primary hemochromatosis patients: a systematic review.

Hereditary hemochromatosis (HH) is a genetic disorder that causes excess absorption of iron and can lead to a variety of complications including liver cirrhosis, arthritis, abnormal skin pigmentation, cardiomyopathy, hypogonadism, and diabetes. Hemojuvelin (HJV) is the causative gene of a rare subtype of HH worldwide. This study aims to systematically review the genotypic and phenotypic spectra of HJV-HH in multiple ethnicities, and to explore the genotype-phenotype correlations. A comprehensive search of PubMed database was conducted. Data were extracted from 57 peer-reviewed original articles including 132 cases with HJV-HH of multiple ethnicities, involving 117 biallelic cases and 15 heterozygotes. Among the biallelic cases, male and female probands of Caucasian ancestry were equally affected, whereas males were more often affected among East Asians (P=1.72×10-2). Hepatic iron deposition and hypogonadism were the most frequently reported complications. Hypogonadism and arthropathy were more prevalent in Caucasians than in East Asians (P=9.30×10-3, 1.69×10-2). Among the recurrent mutations, G320V (45 unrelated cases) and L101P (7 unrelated cases) were detected most frequently and restricted to Caucasians. [Q6H; C321*] was predominant in Chinese patients (6 unrelated cases). I281T (Chinese and Greek), A310G (Brazilian and African American), and R385* (Italian and North African) were reported across different ethnicities. In genotype-phenotype correlation analyses, 91.30% of homozygotes with exon 2-3 mutations developed early-onset HH compared to 66.00% of those with exon 4 mutations (P=2.40×10-2). Hypogonadism occurred more frequently in homozygotes with missense mutations (72.55%) than in those with nonsense mutations (35.71%; P=2.43×10-2). Liver biopsy was accepted by more probands with frame-shift or missense mutations (85.71% and 60.78%, respectively) than by those with nonsense mutations (28.57%; P=2.37×10-2, 3.93×10-2). The present review suggests that patients' ethnicity, geographical region, and genetic predisposition should be considered in the diagnosis, prognosis and management of HJV-HH.

Sex-Specific Prevalence of Diabetes and Cardiovascular Risk Factors in the Middle-Aged Population of China: A Subgroup Analysis of the 2007-2008 China National Diabetes and Metabolic Disorders Study.

The sex difference in the prevalence rates of diabetes and cardiovascular diseases (CVDs) among the middle-aged population in China remain largely unknown. Therefore, we analyzed differences in the prevalence of diabetes, self-reported CVDs, and some CVD risk factors among men and women in the middle-aged population (30-49 years) and in individuals aged 50 years and older using data from the China National Diabetes and Metabolic Disorders Study of 2007-2008. Middle-aged men appeared to have significantly a higher prevalence of diabetes and self-reported CVDs than middle-aged women (8.07% vs 5.06% for diabetes, P < 0.001; 0.64% vs 0.22% for CVDs, P < 0.001). Men also showed higher rates of central obesity, hypertension, and dyslipidemia than women (all P < 0.01). Compared with women, men were more likely to drink alcohol and smoke cigarettes but less likely to be under diet control. The sex-specific differences in prediabetes, CVD, and CVD risk factors between men and women were diminished or even reversed in the population aged 50 years and older. No sex-specific differences were found in the prevalences of a family history of diabetes, coronary heart disease, and hypertension (P > 0.05) in middle-aged population. Specific strategies to reduce modifiable risk factors for the prevention and control of diabetes and CVD may be warranted in this population.