Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled With Metformin Alone or With Sulfonylurea: The PIONEER 3 Randomized Clinical Trial.

Importance: Phase 3 trials have not compared oral semaglutide, a glucagon-like peptide 1 receptor agonist, with other classes of glucose-lowering therapy. Objective: To compare efficacy and assess long-term adverse event profiles of once-daily oral semaglutide vs sitagliptin, 100 mg added on to metformin with or without sulfonylurea, in patients with type 2 diabetes. Design, Setting, and Participants: Randomized, double-blind, double-dummy, parallel-group, phase 3a trial conducted at 206 sites in 14 countries over 78 weeks from February 2016 to March 2018. Of 2463 patients screened, 1864 adults with type 2 diabetes uncontrolled with metformin with or without sulfonylurea were randomized. Interventions: Patients were randomized to receive once-daily oral semaglutide, 3 mg (n = 466), 7 mg (n = 466), or 14 mg (n = 465), or sitagliptin, 100 mg (n = 467). Semaglutide was initiated at 3 mg/d and escalated every 4 weeks, first to 7 mg/d then to 14 mg/d, until the randomized dosage was achieved. Main Outcomes and Measures: The primary end point was change in glycated hemoglobin (HbA1c), and the key secondary end point was change in body weight, both from baseline to week 26. Both were assessed at weeks 52 and 78 as additional secondary end points. End points were tested for noninferiority with respect to HbA1c (noninferiority margin, 0.3%) prior to testing for superiority of HbA1c and body weight. Results: Among 1864 patients randomized (mean age, 58 [SD, 10] years; mean baseline HbA1c, 8.3% [SD, 0.9%]; mean body mass index, 32.5 [SD, 6.4]; n=879 [47.2%] women), 1758 (94.3%) completed the trial and 298 prematurely discontinued treatment (16.7% for semaglutide, 3 mg/d; 15.0% for semaglutide, 7 mg/d; 19.1% for semaglutide, 14 mg/d; and 13.1% for sitagliptin). Semaglutide, 7 and 14 mg/d, compared with sitagliptin, significantly reduced HbA1c (differences, -0.3% [95% CI, -0.4% to -0.1%] and -0.5% [95% CI, -0.6% to -0.4%], respectively; P < .001 for both) and body weight (differences, -1.6 kg [95% CI, -2.0 to -1.1 kg] and -2.5 kg [95% CI, -3.0 to -2.0 kg], respectively; P < .001 for both) from baseline to week 26. Noninferiority of semaglutide, 3 mg/d, with respect to HbA1c was not demonstrated. Week 78 reductions in both end points were statistically significantly greater with semaglutide, 14 mg/d, vs sitagliptin. Conclusions and Relevance: Among adults with type 2 diabetes uncontrolled with metformin with or without sulfonylurea, oral semaglutide, 7 mg/d and 14 mg/d, compared with sitagliptin, resulted in significantly greater reductions in HbA1c over 26 weeks, but there was no significant benefit with the 3-mg/d dosage. Further research is needed to assess effectiveness in a clinical setting. Trial Registration: ClinicalTrials.gov Identifier: NCT02607865.

Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus living in hot climates.

AIMS: Patients with type 2 diabetes mellitus (T2DM) have increased risk of adverse events (AEs; e.g. dehydration, hypoglycaemia) in hot weather. This analysis assessed the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, in patients with T2DM who live in hot climates. METHODS: This post hoc analysis evaluated patients with T2DM using pooled data from four 26-week, placebo-controlled studies (N=2,313) and data from a 104-week, active-controlled study (add-on to metformin vs glimepiride; N=1,450). Changes in HbA1c, fasting plasma glucose (FPG), body weight and blood pressure (BP) were assessed in subsets of patients living in hot climates (pooled, placebo-controlled studies, n=611; active-controlled study, n=307) and those living in other climates (i.e. other climate subset; pooled, placebo-controlled studies, n=1,702; active-controlled study, n=1,143). Safety was assessed based on AE reports. RESULTS: Canagliflozin 100 and 300 mg lowered HbA1c, FPG, body weight and BP vs placebo over 26 weeks and glimepiride over 104 weeks in the hot climate subsets. Canagliflozin was generally well tolerated in the hot climate subsets, with a higher incidence of AEs related to the mechanism of SGLT2 inhibition (i.e. genital mycotic infections). Volume depletion-related AEs were low across groups. CONCLUSION: Canagliflozin improved glycaemic control, lowered body weight and BP, and was generally well tolerated in patients with T2DM living in hot climates compared with placebo over 26 weeks or glimepiride over 104 weeks. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT01081834, NCT01106677, NCT01106625, NCT01106690, NCT00968812.

[Prevalence of depression and anxiety in a cohort of 761 obese patients: impact in adherence to therapy and its outcome]. / Prevalencia de depresión y ansiedad en una cohorte de 761 obesos: implicancias en la adherencia al tratamiento y sus resultados.

OBJECTIVE: To determine the prevalence of psychiatric disorders in 761 obese patients, prospectively assessing their impact in both adherence to therapy and its outcome. MATERIAL AND METHODS: Overweight and obesity were defined by body mass index (BMI), depression and anxiety according to "The Hospital Anxiety and Depressio Scale". Patients received a physical and biochemical evaluation, a hypochaloric diet and a training plan. Sibutramine was prescribed as anti-obesity drug. RESULTS: The mean age was 31,28 (SD 11,26) years. 74.77% were women. The mean weight was 91.36 kg with a BMI of 34,49 Kg/m2 (SD 6,29). The prevalence of possible, probable and definite anxiety/depression was: 56.3%/22.0%, 29.8%/6.2%, and 7.2%/0.8% respectively. Both initial and final weight and BMI were higher in definite and probable depression respectively, with a minor percentage of weight loss likewise. CONCLUSIONS: The studied psychiatric disturbances were prevalent in our population. Initial and final weight and BMI were higher in groups with more severe anxiety or depression. The percentage of weight loss and adherence to therapy were greater in groups of milder psychiatric disorders.

Obesity and family history of diabetes as risk factors of impaired fasting glucose: implications for the early detection of prediabetes.

OBJECTIVE: To determine whether the association between family history of diabetes (FHD) and impaired fasting glucose (IFG) is independent of body mass index (BMI) in children and adolescents. METHODS: In all 443 (11.9%) children and adolescents with FHD, and 3280 (88.1%) without FHD were enrolled in a population-based cross-sectional study. Eligible subjects to participate were apparently healthy children and adolescents aged 7-15 yr from Middle and Northern Mexico. Obesity was defined by age- and gender-specific BMI >or= 95th percentile. FHD was defined as positive if at least one first degree relative had diabetes. The IFG was defined by fasting plasma glucose >or= 100 mg/dL and < 126 mg/dL. RESULTS: IFG was identified in 390 (88.0%) and 62 (1.9%) children and adolescents with and without FHD, respectively. In the group with positive FHD, IFG was diagnosed in 146 (37.4%), 79 (20.2%), and 165 (42.3%) children and adolescents who were obese, overweight, and normal-weight, respectively. On the other hand, in the group without FHD, IFG was identified in 21 (33.9%), 14 (22.6%), and 27 (43.5%) children and adolescents who were obese, overweight, and normal-weight, respectively. In the overall population, the age-, sex-, and BMI-adjusted logistic regression analysis showed a strong and independent association between FHD and IFG [odds ratio (OR) -11.7; 95% CI 9.5-21.2]. This association remained strong for girls and boys in a subsequent analysis stratified for BMI category. CONCLUSIONS: The presence of FHD in a first degree relative is associated with IFG, even in the absence of obesity.

Distribution of fasting plasma glucose and prevalence of impaired fasting glucose, impaired glucose tolerance and type 2 diabetes in the Mexican paediatric population.

Published data on the distribution of fasting plasma glucose (FPG) in children are scarce. We therefore set out to examine the distribution of FPG and determine the prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and type 2 diabetes (T2-DM) in Mexican children aged 6-18 years in a community-based cross-sectional study. A total of 1534 apparently healthy children were randomly enrolled and underwent an oral glucose tolerance test. IFG was defined by an FPG value between >or=100 and <126 mg/dL, IGT by glucose concentration 2-h post-load between >or=140 and <200 mg/dL, and T2-DM by glucose concentration 2-h post-load >or=200 mg/dL. The FPG level at the 75(th) percentile of distribution was 98.0, 100.0 and 99.0 mg/dL for children aged 6-9, 10-14 and 15-18 years, respectively; the 95(th) percentile of FPG was greater than 100 mg/dL for all the age strata. In the population overall, the prevalences of IFG, IGT, and T2-DM were 18.3%, 5.2% and 0.6%, respectively. Among obese children and adolescents, the prevalences of IFG, IGT, IFG + IGT and T2-DM were 19.1%, 5.7%, 2.5% and 1.3%. Our study shows a high prevalence of prediabetes and is the first that reports the distribution of FPG in Mexican children and adolescents.

[Morbidity and mortality by ischemic heart disease and stroke in Mexico. 2005]. / Morbilidad y mortalidad de la enfermedad isquémica del corazón y cerebrovascular en México, 2005.

Cardiovascular diseases are the main cause of death and disability in México. 25% of deaths under 60 years of age are related to chronic degenerative diseases. These disorders are more common in developing countries and are caused by an excessive intake of fatty acids, sodium, alcohol, tobacco consumption and decrease in physical activity. The prevalence of risk factors is increasing not only in adult population but also in youth and children. Data from the Department of Epidemiology from the Mexican Ministry of Health in the period between 1998 and 2000 showed that the death caused by coronary artery disease was more frequent in men (55%) than women (45%) and acute coronary syndrome was responsible for deaths in 83.5% of men and 76.8% in women. Primary Prevention Programs are necessary to decrease the impact of cardiovascular diseases.

Obesity risk factors in the ISAAC (International Study of Asthma and Allergies in Childhood) in Mexico City.

BACKGROUND: The International Study of Asthma and Allergies in Childhood (ISAAC) has promoted surveys in asthma and allergic diseases using standardized methodologies including validated questionnaires. Many items in the questionnaires have also been implied in the overweight and obesity etiology. OBJECTIVE: To describe the factors associated with obesity in subjects of 6-7 years and 13-14 years in the ISAAC survey in Mexico City. MATERIAL AND METHODS: Data were obtained from questionnaires of children participating in a phase 3b ISAAC survey. Logistic regression was used to determine the obesity risks factors. RESULTS: The factors related to obesity were weekly consumption of meat (+, positive relationship), vegetables, pasta, rice (+) and quartiles of birth weight (+) in boys of 6-7 years. Having suffered eczema at any time, weekly consumption of fruit, pasta, butter, nuts, potato (+), fast food (+), daily TV viewing (+) in girls of 6-7years. Having suffered eczema at any time, weekly consumption of pasta (+), butter, potato, weekly physical exercise in boys of 13-14 years; weekly consumption of pasta, margarine, milk, fast food (+), currently smoking in girls of 13-14 years. CONCLUSIONS: There were not common factor patterns for the different groups, birth weight, fast food, TV viewing and lack of exercise have been previously related to pediatric obesity. Asthma was not associated with a higher risk of obesity but medical history of eczema was associated with lower risk of obesity in the 6-7 years girls, and 13-14 years boys. The present study provides the bases for future epidemiological studies and gives some clues on possible public health actions.

Percentile distribution of the waist circumference among Mexican pre-adolescents of a primary school in Mexico City.

AIM: The aim of this study is to describe the percentile distribution of the waist circumference in Mexican pre-pubertal children living in an urban, middle-income area. METHODS: Children, aged 6-10, from a primary school, located in a middle-income area in Mexico City were included (n=833). Anthropometric measurements were made in the case of all children by using standardized procedures. RESULTS: The prevalence of obesity and overweight was greater among boys (p<0.001). Of them, 30 were obese (7.2%) and 47 were overweight (11.4%). Girls had a prevalence of obesity of 2.8% and of overweight of 8.8%. Boys had greater waist circumference than girls (p<0.001). This observation was independent from differences in age or body mass index (BMI). The distribution of the waist circumference was shifted towards higher values among boys. The values corresponding to the 85th percentile ranged, in boys aged 6-10, between 62.9 and 85.9 cm. By contrast, for girls, those values were 66.8 and 72.08 cm, respectively. A receiver-operator curve was constructed in order to identify the waist circumference most likely to be associated with a BMI of > 85th percentile. We found that age- and sex-specific cut-off points are required for the detection of central adiposity in children aged 6-10. CONCLUSIONS: The percentile distribution of the waist circumference in Mexican pre-pubertal children living in urban, middle-income areas is described in this study. Moreover, included are the cut-off points most likely to be associated with increased adiposity. This information can be used for defining abdominal obesity in paediatric populations.

The high prevalence of overweight and obesity in Mexican children.

OBJECTIVE: To establish the prevalence of overweight and obesity in Mexican children 10 to 17 years of age according to the percentiles from both the Centers of Disease Control and Prevention (CDC) and the International Obesity Task Force (IOTF). RESEARCH METHODS AND PROCEDURES: Heights and weights were measured in children from nationally representative, randomly chosen households in the Mexican National Health Survey 2000. The study population consisted of 7862 boys and 8947 girls, 10 to 17 years of age. Measurements used were the percentage of children in the corresponding BMI categories for overweight and obesity specified by the CDC and the IOTF BMI percentiles. RESULTS: The children were short, with mean Z scores for height by age varying from - 0.62 +/- 1.26 to -1.12 +/- 1.06 in boys and from -0.45 +/- 1.25 to -1.19 +/- 1.12 in girls. CDC-based overweight prevalences varied by age from 10.8% to 16.1% in boys and 14.3% to 19.1% in girls, with obesity prevalences from 9.2% to 14.7% in boys and 6.8% to 10.6% in girls; these prevalences did not relate to stunting. IOTF-based excess weight prevalences were similar, with higher overweight rates (boys, 15.4% to 18.8%; girls, 18.4% to 22.3%) but lower obesity rates (boys, 6.1% to 9%; girls, 5.9% to 8.2%). DISCUSSION: Mexican children have one-half the overweight/obesity prevalences of U.S. Mexican-American children; however, there are higher rates in Northern Mexico, which is closer to the U.S. These escalating rates of excess weight demand new prevention, as well as management, policies.

Morbilidad y mortalidad de la enfermedad isquémica del corazón y cerebrovascular en México, 2005 / Morbidity and mortality by ischemic heart disease and stroke in Mexico. 2005

Cardiovascular diseases are the main cause of death and disability in México. 25% of deaths under 60 years of age are related to chronic degenerative diseases. These disorders are more common in developing countries and are caused by an excessive intake of fatty acids, sodium, alcohol, tobacco consumption and decrease in physical activity. The prevalence of risk factors is increasing not only in adult population but also in youth and children. Data from the Department of Epidemiology from the Mexican Ministry of Health in the period between 1998 and 2000 showed that the death caused by coronary artery disease was more frequent in men (55%) than women (45%) and acute coronary syndrome was responsible for deaths in 83.5% of men and 76.8% in women. Primary Prevention Programs are necessary to decrease the impact of cardiovascular diseases.

Eficacia y tolerancia de acarbose en pacientes diabéticos no dependientes de insulina / Efficacy and tolerance of acarbose in non-insulin dependent diabetes

El acarbose es un inhibidor competitivo de aglucosidasa que reduce el aumento postprandial de glucosa e insulina. En este estudio doble ciego, cruzado, con distribución de tratamientos al azar, se administró acarbose o placebo a un grupo de pacientes con DMNID crónicamente descontrolados que recibían sulfonilureas. Los pacientes continuaron su tratamiento previo y fueron distribuidos al azar en dos secuencias: en la A recibieron acarbose 100 mg tres veces al día 12 semanas, dos semanas de placebo tres veces al día (periodo de lavado) y finalmente placebo tres veces al día 12 semanas. En la secuencia B el orden fue inverso al anterior (placebo-placebo-acarbose). Se incluyeron 16 pacientes en cada secuencia. Se excluyeron tres de la secuencia A: uno por efectos colaterales, uno por dolor neuropático y uno por cambio de domicilio. De la secuencia B se excluyó uno por no tomar la sulfonilurea. Se observó una disminución discreta pero significativa del peso con acarbose comparado con placebo en ambas secuencias. Se observaron reducciones significativas de glucosa postprandial con el acarbose en ambas secuencias; también se observaron reducciones en los niveles de glucosa de ayunas en algunas visitas. Aunque los valores promedio de HbA1c y triglicéridos fueron menores con acarbose, la diferencia con el placebo no fue estadísticamente significativa. El acarbose fue tolerado bien en general, ya que si bien casi todos los pacientes mostraron efectos colaterales, sólo tuvo que suspenderse en uno. El acarbose es un recurso terapéutico útil en combinación con sulfonilureas en diabéticos no insulinodependiente