Efficacy and safety of evogliptin in the treatment of type 2 diabetes mellitus in a Brazilian population: a randomized bridging study.

BACKGROUND: Evogliptin (EVO) is a potent and selective dipeptidyl peptidase-4 inhibitor (DPP4i) developed for the treatment of type 2 diabetes mellitus (T2DM). DPP4is are known to exhibit a better glucose-lowering effect in Asians compared to other ethnic groups. Once EVO's clinical development program was conducted in Asian patients, this bridging study was designed to validate for the Brazilian population the efficacy and safety of the approved dose regimen (once-daily 5.0 mg). METHODS: In this randomized, double-blind, double-dummy, parallel trial, 146 patients with T2DM with inadequate glycemic control on diet and exercise (7.5% ≤ HbA1c ≤ 10.5%) were randomly assigned to a 12-week once-daily treatment with EVO 2.5 mg (N = 35), EVO 5 mg (N = 36), EVO 10 mg (N = 36), or sitagliptin (SITA) 100 mg (N = 39). Absolute changes (Week 12-baseline) in HbA1c, fasting plasma glucose (FPG) and body weight (BW) were obtained. One-sided one sample t test was used to determine if mean HbA1c reduction in each group was < - 0.5% (beneficial metabolic response). An analysis of covariance estimated the change in HbA1c and FPG adjusted by baseline HbA1c, FPG, body mass index (BMI) and study site. Response rates to treatment were also established. No between-group statistical comparisons were planned. RESULTS: HbA1c mean reductions were - 1.26% (90% CI - 1.7%, - 0.8%), - 1.12% (90% CI - 1.4%, - 0.8%), - 1.29% (90% CI - 1.6%, - 1.0%), and - 1.15% (90% CI - 1.5%, - 0.8%) in groups EVO 2.5 mg, EVO 5 mg, EVO 10 mg, and SITA 100 mg, respectively. FPG levels showed a mean increase of 10.89 mg/dL in group EVO 2.5 mg, with significant mean reductions of - 18.94 mg/dL, - 21.17 mg/dL, and - 39.90 mg/dL in those treated with EVO 5 mg, EVO 10 mg, and SITA 100 mg, respectively. BW showed significant reductions of approximately 1 kg in patients treated with EVO 5 mg, EVO 10 mg, and SITA 100 mg. Mean adjusted reductions of HbA1c and FPG levels confirmed the significant clinical benefit of all study treatments. The clinical benefit of EVO's "target" dose (5 mg) was confirmed. No safety concerns were identified. CONCLUSIONS: These results validate for the Brazilian population the approved dose regimen of EVO (once-daily 5 mg).Trial registration ClinicalTrials.gov Identifier: NCT02689362 (first posted on 02/23/2016).

Hypoglycemia incidence and awareness among insulin-treated patients with diabetes: the HAT study in Brazil.

BACKGROUND: Hypoglycemia affects patient safety and glycemic control during insulin treatment of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). The Hypoglycemia Assessment Tool study in Brazil aimed to determine the proportion of patients experiencing hypoglycemic events and to characterize patient awareness and fear about hypoglycemia, among insulin-treated T1DM or T2DM patients. METHODS: This was a non-interventional, multicenter study, with a 6-month retrospective and a 4-week prospective evaluation of hypoglycemic events. Patients completed a questionnaire at baseline and at the end of the study, and also a patient diary. The answers 'occasionally' and 'never' to the question 'Do you have symptoms when you have a low sugar level?' denoted impaired hypoglycemia awareness. Fear was reported on a 10-point scale, from 'not afraid at all' to 'absolutely terrified'. RESULTS: From 679 included patients, 321 with T1DM and 293 T2DM, median age of 33.0 and 62.0 years, 59% and 56% were female, and median diabetes duration was 15.0 and 15.0 years, respectively. Median time of insulin use was 14.0 and 6.0 years. During the prospective period, 91.7% T1DM and 61.8% T2DM patients had at least one hypoglycemic event. In the same period, 54.0% T1DM and 27.4% T2DM patients had nocturnal hypoglycemia, 20.6% T1DM and 10.6% T2DM patients had asymptomatic hypoglycemia, and severe events occurred in 20.0% and 10.3%, respectively. At baseline, 21.4% T1DM and 34.3% T2DM had hypoglycemia unawareness. The mean score of hypoglycemia fear was 5.9 ± 3.1 in T1DM and 5.4 ± 3.9 in T2DM. The most common attitude after hypoglycemic events were to increase calorie intake (60.3%) and blood glucose monitoring (58.0%) and to reduce or skip insulin doses (30.8%). CONCLUSIONS: Referred episodes of hypoglycemia were high, in both T1DM and T2DM insulin users. Patient attitudes after hypoglycemia, such as reduction in insulin and increase in calorie intake, can affect diabetes management. These findings may support clinicians in tailoring diabetes education and insulin treatment for patients with diabetes, in order to improve their glycemic control while reducing the risk of hypoglycemic events.

Clinical inertia on insulin treatment intensification in type 2 diabetes mellitus patients of a tertiary public diabetes center with limited pharmacologic armamentarium from an upper-middle income country.

BACKGROUND: Clinical inertia is related to the difficulty of achieving and maintaining optimal glycemic control. It has been extensively studied the delay of the period to insulin introduction in type 2 diabetes mellitus (T2DM) patients. This study aims to evaluate clinical inertia of insulin treatment intensification in a group of T2DM patients followed at a tertiary public Diabetes Center with limited pharmacologic armamentarium (Metformin, Sulphonylurea and Human Insulin). METHODS: This is a real life retrospective record based study with T2DM patients. Demographic, clinical and laboratory characteristics were reviewed. Clinical inertia was considered when the patients did not achieve the individualized glycemic goals and there were no changes on insulin daily dose in the period. RESULTS: We studied 323 T2DM patients on insulin therapy (plus Metformin and or Sulphonylurea) for a period of 2 years. The insulin daily dose did not change in the period and the glycated hemoglobin (A1c) ranged from 8.8 + 1.8% to 8.7 ± 1.7% (basal vs 1st year; ns) and to 8.5 ± 1.8% (basal vs 2nd year; p = 0.035). The clinical inertia prevalence was 65.8% (basal), 61.9% (after 1 year) and 58.2% (after 2 years; basal vs 1st year vs 2nd year; ns). In a subgroup of 100 patients, we also studied the first 2 years after insulin introduction. The insulin daily dose ranged from 0.22 ± 0.12 to 0.32 ± 0.24 IU/kg of body weight/day (basal vs 1st year; p < 0.001) and to 0.39 ± 0.26 IU/kg of body weight/day (basal vs 2nd year; p < 0.05). The A1c ranged from 9.6 + 2.1% to 8.6 + 2% (basal vs 1st year; p < 0.001) and to 8.7 + 1.7% (1st year vs 2nd year; ns). The clinical inertia prevalence was 78.5% (at the moment of insulin therapy introduction), 56.2% (after 1 year; p = 0.001) and 62.2% (after 2 years; ns). CONCLUSION: Clinical inertia prevalence ranged from 56.2 to 78.5% at different moments of the insulin therapy (first 2 years and long term) of T2DM patients followed at a tertiary public Diabetes Center from an upper-middle income country with limited pharmacologic armamentarium.

A randomised, double-blind, trial of the safety and efficacy of omarigliptin (a once-weekly DPP-4 inhibitor) in subjects with type 2 diabetes and renal impairment.

AIMS: To assess the safety and efficacy of omarigliptin in subjects with type 2 diabetes mellitus (T2DM) and chronic renal impairment (RI). METHODS: Patients with T2DM with moderate RI (estimated glomerular filtration rate [eGFR] ≥30 to <60 mL/min/1.73 m2 ) (N=114), severe RI (eGFR <30 mL/min/1.73 m2 ) (N=55) or end-stage renal disease on dialysis (N=44), who were either not on an antihyperglycaemic agent therapy for at least 12 weeks at screening, washed-off of oral antihyperglycaemic agent monotherapy or low-dose dual combination therapy, or on insulin monotherapy, with baseline glycated haemoglobin (HbA1c) of 6.5%-10.0% were randomised to omarigliptin or to placebo for 24 weeks (primary end-point) followed by a 30-week period with subjects on placebo switched to blinded glipizide (if not on insulin). RESULTS: After 24 weeks, from a mean baseline HbA1c of 8.4% in the omarigliptin group and 8.3% in the placebo group, the least squares mean (95% CI) change from baseline in HbA1c in the overall population (all renal strata combined) was -0.77% (-1.00 to -0.54) in the omarigliptin group and -0.44% (-0.67 to -0.21) in the placebo group; between-group difference of -0.33% (-0.63 to -0.02); P=0.035. After 24 weeks, the incidences of subjects with symptomatic hypoglycaemia, one or more adverse event (AE), drug-related AE, serious AE and discontinuation due to an AE were similar in the omarigliptin and placebo groups. CONCLUSIONS: In this study in subjects with T2DM and RI, relative to placebo, omarigliptin provided clinically meaningful reductions in HbA1c, had a similar incidence of symptomatic hypoglycaemia and was generally well tolerated.

Updated risk factors should be used to predict development of diabetes.

AIMS: Predicting incident diabetes could inform treatment strategies for diabetes prevention, but the incremental benefit of recalculating risk using updated risk factors is unknown. We used baseline and 1-year data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial to compare diabetes risk prediction using historical or updated clinical information. METHODS: Among non-diabetic participants reaching 1year of follow-up in NAVIGATOR, we compared the performance of the published baseline diabetes risk model with a "landmark" model incorporating risk factors updated at the 1-year time point. The C-statistic was used to compare model discrimination and reclassification analyses to demonstrate the relative accuracy of diabetes prediction. RESULTS: A total of 7527 participants remained non-diabetic at 1year, and 2375 developed diabetes during a median of 4years of follow-up. The C-statistic for the landmark model was higher (0.73 [95% CI 0.72-0.74]) than for the baseline model (0.67 [95% CI 0.66-0.68]). The landmark model improved classification to modest (<20%), moderate (20%-40%), and high (>40%) 4-year risk, with a net reclassification index of 0.14 (95% CI 0.10-0.16) and an integrated discrimination index of 0.01 (95% CI 0.003-0.013). CONCLUSIONS: Using historical clinical values to calculate diabetes risk reduces the accuracy of prediction. Diabetes risk calculations should be routinely updated to inform discussions about diabetes prevention at both the patient and population health levels.

Diabetes mellitus no Brasil: características clínicas, padrão de tratamento e custos associados ao cuidado da doença / Diabetes Mellitus in Brazil: clinical characteristics, standard treatment choice and cost

Objetivo: Descrever a utilização de recursos de saúde associados ao tratamento do Diabetes Mellitus tipo 2 (DM2) no sistema público de saúde brasileiro, assim como o padrão de tratamento e seus eventos adversos, a ocorrência de complicações vasculares e o controle metabólico nos pacientes. Métodos: Estudo observacional, retrospectivo, conduzido em 4 centros do Sistema Único de Saúde envolvendo pacientes com DM2. Os dados foram coletados dos prontuários médicos de setembro a dezembro de 2013. Foi conduzida análise descritiva considerando três faixas de duração da doença desde o seu diagnóstico e a estratificação dos pacientes de acordo com o período recordatório e presença de complicações vasculares. Resultados: 161 pacientes foram analisados. Os principais esquemas terapêuticos utilizados foram a combinação de metformina, insulina NPH e insulina regular; de glibenclamida e metformina; e metformina isolada. A associação metformina e insulina apresentou maior frequência de eventos adversos (28,9%) e a glibenclamida, metformina e insulina, menor frequência (5,7%). A maioria dos pacientes mostrou complicações microvasculares, sendo nefropatia e neuropatia frequentes em todos os estratos analisados. Em pacientes com DM2 avançado (≥ 15 anos de duração), a retinopatia mostrou-se prevalente. A frequência de eventos macrovasculares variou de 21,3% a 37,9% entre os grupos, sendo a doença coronariana a mais frequente. Um custo total médio de R$ 931,88±1.400,75 por paciente foi observado para os pacientes sem complicações vasculares e de R$ 1.212,37±1.012,38 para aqueles com complicações. Conclusão: Informações relevantes sobre o manejo de pacientes brasileiros com DM2 foram descritas, sugerindo alta frequência de complicações vasculares e maiores custos associados a elas.

Objective: The aim of this study is to describe the use of public health resources to Type 2 Diabetes Mellitus (T2DM) and its costs in Brazil. Furthermore, we describe the standard treatment choice and its related adverse events as well as patients' metabolic control and vascular complications. Methods: This observational and retrospective study was conducted in four public health centers from Brazilian Public Health System (SUS); a secondary assistance level for long-term treatment for outpatients with T2DM. Data were collected from medical records from September to December 2013. A descriptive analysis is available for three groups according to time of disease since diagnosis. The recall and vascular complications were also considered. Results: 161 patients were studied. The most frequent treatments were metformin in monotherapy, metformin + NPH insulin + regular insulin and metformin + glibenclamide. Metformin + insulin therapy had the highest rate of adverse events (28.9%), while glibenclamide + metformin + insulin therapy, the lowest rate (5.7%). The majority of patients developed microvascular complications, specially nephropathy and neuropathy. Retinopathy was the most frequent complication for the group of patients with end stage T2DM (≥ 15 years). The frequency of macrovascular events ranged from 21.3% to 37.9% between groups. Coronary disease was the most frequent macrovascular complications. The mean cost per patient was R$ 1.212,37±1.012,38 for patient group presenting vascular complications and R$ 931,88±1.400,75 for the group not presenting complications. Conclusion: We describe current use of public health resources regarding T2DM treatment in Brazil, as well as T2DM treatment´s characteristics.

The cost of type 2 diabetes in Brazil: evaluation of a diabetes care center in the city of São Paulo, Brazil.

BACKGROUND: The worldwide increase of diabetes, a long duration, slow progression disease, impacts health care costs. The aim of this study was to estimate, from the society's perspective, the annual cost per patient with Type 2 Diabetes (T2DM) at a specialized, outpatient center in the city of São Paulo, capital of São Paulo state, Brazil. METHODS: Data from 209 patients were collected during the years 2009 and 2010 in a São Paulo diabetes care center which is part of the tertiary sector of SUS, Brazil's National Health Care System. Data were collected by means of interviews and reviews of medical charts, and the quality of life was appraised using the SF36-v2 questionnaire. Direct medical costs were divided in five categories: 1) medication; 2) laboratory tests; 3) hospitalizations and procedures; 4) reactive strips for capillary blood glucose monitoring; and 5) medical consultations. Direct non-medical costs referred to transportation of patient and companion for treatment. Indirect costs included early retirements, sick leave and absenteeism in the workplace. Statistical analysis of the data was performed by the SPSS software, version 17.0. RESULTS: Our sample comprised 122 women (58%) and 87 men (42%), with mean age of 63 years and average diabetes duration of 13 years. The mean annual cost was US$ 1,844 per patient, out of which US$ 1,012 corresponded to direct costs (55%) and US$ 831 to indirect costs (45%). From the direct medical costs, medications accounted for the greatest proportion (42%), followed by reactive strips (27%), hospitalizations and procedures (14%), laboratory tests and image examinations (7%), as well as medical consultations (4%). Non-medical costs (transportation) corresponded to 7% of the total direct costs. Besides, the results indicated that men have better quality of life than women. CONCLUSION: This study demonstrated a high T2DM cost in Brazil, considering the governmental per capita expenses in health care, which accounted for US$ 466 in 2010 (World Health Statistics 2013 96-104 2013). Taking into account the high prevalence of the disease (IDF Diabetes Atlas. 5th edition. 29-48 2012), this survey recommends the enforcement of policies for the prevention of diabetes and its complications, and urges for better allocation of healthcare resources.

Evolving metformin treatment strategies in type-2 diabetes: from immediate-release metformin monotherapy to extended-release combination therapy.

Over the last 40 years, metformin has revolutionized the treatment of type-2 diabetes worldwide and is still the most influential oral antidiabetic drug today. International guidelines now recommend that patients with type-2 diabetes are started on metformin therapy as soon as they are diagnosed, as it has been shown to improve long-term clinical outcomes compared with initial management with diet alone, without increasing the risk of developing hypoglycemia or weight gain. The older, immediate-release formulation of metformin does have some limitations, with incidence of gastrointestinal adverse effects restricting the dose in some patients, forming a barrier to treatment adherence, and subsequent glycemic control. However, the second-generation extended-release formulation (met XR) has the potential to overcome these challenges. In this review, we provide an overview of the evidence supporting the use of metformin as the first-line gold standard for type-2 diabetes management and the expansion of its potential roles for the future. We also consider the advantages of met XR, in terms of its tolerability and convenient dose regimen, and review therapeutic options for when disease progression inevitably leads to inadequate control with monotherapy. These therapy options include the synergistic potential of combination strategies with met XR and dipeptidyl peptidase 4 inhibitors, a combination that has also been indicated for early-stage use (at diagnosis) as a potential method for preserving ß-cell function.

Poor glycaemic control in Brazilian patients with type 2 diabetes attending the public healthcare system: a cross-sectional study.

OBJECTIVES: To describe the clinical profile of Brazilian patients with type 2 diabetes attending the public healthcare system and identify factors associated with poor glycaemic control. DESIGN: Cross-sectional study. SETTING: 14 centres in five regions of Brazil, including primary care units and outpatient clinics of University Hospitals. PARTICIPANTS: Patients with type 2 diabetes attending outpatient clinics of public healthcare system. MAIN OUTCOME MEASURED: Glycated haemoglobin (HbA1c), centrally measured by high-performance liquid chromatography (National Glycohemoglobin Standardization Program certified). RESULTS: A total of 5750 patients aged 61±10 years, with 11±8 years of diabetes duration (66% women, 56% non-white, body mass index: 28.0±5.3 kg/m(2)) were analysed. Mean HbA1c was 8.6±2.2%, and median HbA1c was 8.1% (6.9% to 9.9%). HbA1c <7% was observed in only 26% of patients. Mean HbA1c was higher (p < 0.01) in the North (9.0±2.6%) and Northeast (8.9±2.4%) than in the Midwest (8.1±2%), Southeast (8.4±2.1%) and South regions (8.3±1.9%). Using the cut-off value of HbA1c above the median, age (0.986 (0.983 to 0.989)), white ethnicity (0.931 (0.883 to 0.981)) and being from Midwest region (0.858 (0.745 to 0.989)) were protective factors, while diabetes duration (1.015 (1.012 to 1.018)), use of insulin (1.710 (1.624 to 1.802)) and living in the Northeast region (1.197 (1.085 to 1.321)) were associated with HbA1c >8%. CONCLUSIONS: The majority of Brazilian patients with type 2 diabetes attending the public healthcare system had HbA1c levels above recommended targets. The recognition of Northeast residents and non-white patients as vulnerable populations should guide future policies and actions to prevent and control diabetes.

A novel risk classification paradigm for patients with impaired glucose tolerance and high cardiovascular risk.

We used baseline data from the NAVIGATOR trial to (1) identify risk factors for diabetes progression in those with impaired glucose tolerance and high cardiovascular risk, (2) create models predicting 5-year incident diabetes, and (3) provide risk classification tools to guide clinical interventions. Multivariate Cox proportional hazards models estimated 5-year incident diabetes risk and simplified models examined the relative importance of measures of glycemia in assessing diabetes risk. The C-statistic was used to compare models; reclassification analyses compare the models' ability to identify risk groups defined by potential therapies (routine or intensive lifestyle advice or pharmacologic therapy). Diabetes developed in 3,254 (35%) participants over 5 years median follow-up. The full prediction model included fasting and 2-hour glucose and hemoglobin A1c (HbA1c) values but demonstrated only moderate discrimination for diabetes (C = 0.70). Simplified models with only fasting glucose (C = 0.67) or oral glucose tolerance test values (C = 0.68) had higher C statistics than models with HbA1c alone (C = 0.63). The models were unlikely to inappropriately reclassify participants to risk groups that might receive pharmacologic therapy. Our results confirm that in a population with dysglycemia and high cardiovascular risk, traditional risk factors are appropriate predictors and glucose values are better predictors than HbA1c, but discrimination is moderate at best, illustrating the challenges of predicting diabetes in a high-risk population. In conclusion, our novel risk classification paradigm based on potential treatment could be used to guide clinical practice based on cost and availability of screening tests.

Clinical follow-up of two Brazilian subjects with glucokinase-MODY (MODY2) with description of a novel mutation / Seguimento clínico de dois pacientes brasileiros com MODY-glicoquinase (MODY2) e descrição de uma nova mutação

Mutations in the glucokinase gene (GCK) account for many cases of monogenic diabetes featuring maturity-onset diabetes of the young type 2 (MODY2). The clinical pattern of this form of hyperglycemia is rather stable, with a slight elevation in blood glucose, which is usually not progressive. Patients rarely require pharmacological interventions and microvascular complications related to diabetes are unusual. We describe the clinical follow-up of two cases of MODY2 with two different mutations in GCK gene, one in exon 7, p.Glu265Lys (c.793 G> A), which has been previously described, and a novel one, in exon 2, p.Ser69Stop (c. 206C> G). The clinical course of both cases shows similarity in metabolic control of this form of diabetes over the years. Arq Bras Endocrinol Metab. 2012;56(8):490-5.

Mutações no gene da glicoquinase (GCK) são determinantes de uma forma de diabetes monogênico denominada de MODY2 (maturity-onset diabetes of the young, tipo 2). O padrão clínico dessa forma de distúrbio glicêmico é bastante estável, com hiperglicemia leve, geralmente não progressiva. Intervenções farmacológicas raramente são necessárias e complicações crônicas secundárias ao diabetes são infrequentes. Descrevemos o acompanhamento clínico de dois casos de MODY2 com duas mutações diferentes, uma no éxon 7, p.Glu265Lys (c.793 G>A) já descrita anteriormente, e outra inédita no éxon 2 p.Ser69Stop (c. 206C>G). A evolução clínica de ambos os casos demonstra uma semelhança no padrão metabólico dessa forma de diabetes ao longo dos anos. Arq Bras Endocrinol Metab. 2012;56(8):490-5.

Clinical follow-up of two Brazilian subjects with glucokinase-MODY (MODY2) with description of a novel mutation.

Mutations in the glucokinase gene (GCK) account for many cases of monogenic diabetes featuring maturity-onset diabetes of the young type 2 (MODY2). The clinical pattern of this form of hyperglycemia is rather stable, with a slight elevation in blood glucose, which is usually not progressive. Patients rarely require pharmacological interventions and microvascular complications related to diabetes are unusual. We describe the clinical follow-up of two cases of MODY2 with two different mutations in GCK gene, one in exon 7, p.Glu265Lys (c.793 G> A), which has been previously described, and a novel one, in exon 2, p.Ser69Stop (c. 206C> G). The clinical course of both cases shows similarity in metabolic control of this form of diabetes over the years.

Safety and efficacy of saxagliptin in combination with submaximal sulphonylurea versus up-titrated sulphonylurea over 76 weeks.

To assess the long-term efficacy and safety of saxagliptin in patients with type 2 diabetes mellitus inadequately controlled on sulphonylurea monotherapy, 768 patients were randomised to saxagliptin 2.5 or 5 mg in combination with glyburide 7.5 mg versus placebo added to up-titrated glyburide over 76 weeks (24 weeks plus 52-week extension) in this phase 3, double-blind, placebo-controlled trial; 557 patients completed the study, 142 without being rescued. At 76 weeks, adjusted mean changes from baseline HbA(1C) (repeated measures model) (95% confidence interval) for saxagliptin 2.5 mg, saxagliptin 5 mg, and up-titrated glyburide were 0.11% (-0.05, 0.27), 0.03% (-0.14, 0.19), and 0.69% (0.47, 0.92), respectively (post hoc and nominal p < 0.0001 for saxagliptin 2.5 and 5 mg vs. up-titrated glyburide). Adverse event frequency was similar in all treatment groups; reported hypoglycaemia event rates were 24.2%, 22.9%, and 20.6% with saxagliptin 2.5 mg, saxagliptin 5 mg, and up-titrated glyburide, respectively. Saxagliptin plus glyburide provided sustained incremental efficacy compared with up-titrated glyburide over 76 weeks, and was generally well tolerated.

Efficacy and safety of saxagliptin in older patients with type 2 diabetes mellitus.

OBJECTIVE: To assess the safety and efficacy of saxagliptin (5 mg once-daily) in older patients (≥65 years of age) with inadequately controlled type 2 diabetes. RESEARCH DESIGN AND METHODS: In this retrospective subgroup analysis, data from five randomized, double-blind, placebo-controlled, multicenter, 24-week, phase 3 trials were included. The primary studies evaluated saxagliptin 5 mg once-daily (monotherapy or add-on) in patients aged 18-77 years with HbA(1c) ≥7.0% (four studies) or ≥7.5% (add-on to glyburide study) versus placebo. MAIN OUTCOME MEASURES: The primary efficacy endpoint of each study included in this pooled analysis was HbA(1c) change from baseline to week 24. RESULTS: In the five-study pooled population, 279 (16.6%) patients were at least 65 years old; 142 received saxagliptin 5 mg once-daily and 137 received placebo. Treatment groups were well-balanced for baseline characteristics within each study. In older patients, the HbA(1c) adjusted mean change from a baseline of 8.1% was -0.73 ± 0.16% (mean ± SEM) with saxagliptin compared with -0.17 ± 0.14% for placebo from a baseline of 8.0%. Adverse event rates were similar with saxagliptin 5 mg once-daily compared with placebo in older patients. CONCLUSION: The pooled subgroup analysis of saxagliptin 5 mg once-daily monotherapy and add-on therapy trials demonstrated clinically relevant and significant efficacy for reducing HbA(1c) in older (≥65 years) patients. Saxagliptin was well-tolerated in older patients with a low incidence of hypoglycemia and no weight gain.

Consensus report: the current role of self-monitoring of blood glucose in non-insulin-treated type 2 diabetes.

The Coalition for Clinical Research--Self-Monitoring of Blood Glucose Scientific Board convened a meeting in San Francisco, CA, July 20-21, 2011, to discuss the current practice of self-monitoring of blood glucose (SMBG) in non-insulin-treated (NIT) type 2 diabetes mellitus (T2DM). Twelve physician panel members from academia, practice, and government attended this meeting. These experts came from the United States, Brazil, Canada, France, Germany, Italy, and the United Kingdom. In addition, three consultants from Australia, Germany, and the United States contributed to the group's final report. This coalition was organized by Diabetes Technology Society. Self-monitoring of blood glucose was studied from eight perspectives related to patients with NIT T2DM: (1) epidemiological studies; (2) randomized controlled trials (RCT)s and meta-analyses; (3) targets, timing, and frequency of SMBG use; (4) incidence and role of SMBG in preventing hypoglycemia with single-drug regimens and combination regimens consisting of antihyperglycemic agents other than secretagogues and insulin; (5) comparison of SMBG with continuous glucose monitoring; (6) technological capabilities and limitations of SMBG; (7) barriers to appropriate use of SMBG; and (8) methods and end points for appropriate future clinical trials. The panel emphasized recent studies, which reflect the current approach for applying this intervention. Among the participants there was consensus that: SMBG is an established practice for patients with NIT T2DM, and to be most effective, it should be performed in a structured format where information obtained from this measurement is used to guide treatment; New, high-quality efficacy data from RCTs have demonstrated efficacy of SMBG in NIT T2DM in trials reported since 2008; Both patients and health care professionals require education on how to respond to the data for SMBG to be effective; and Additional well-defined studies are needed to assess the benefits and costs of SMBG with end points not limited to hemoglobin A1c.

Aerobic exercise capacity and pulmonary function in athletes with and without type 1 diabetes.

OBJECTIVE: To compare the aerobic exercise capacity and pulmonary function between athletes with and without type 1 diabetes. RESEARCH DESIGN AND METHODS: Fifty-one adult age-matched individuals were assessed in random order to the maximum volume of O(2) consumption (Vo(2 peak max)) (ml/kg/min), anaerobic threshold (ml/kg/min), peak pulmonary ventilation (Ve), heart rate (beats per min), time to exhaustion (min), forced vital capacity (FEV) (%), forced expiratory volume in the first second (FEV1) (%), total lung capacity (TLC) (%), and lung diffusion capacity for carbon monoxide (DL(CO)) (%). Individuals were 27 with type 1 diabetes: 15 athletes (ADM) and 12 nonathletes (NADM); and 24 healthy individuals: 12 ADM and 12 NADM. Duration of diabetes was 14.6 ± 6.2 and 15.2 ± 6.7 years in ADM and NADM, respectively. RESULTS: Vo(2 peak) (max) was higher in ADM than in NADM (P < 0.001). The anaerobic threshold was lower in subjects with type 1 diabetes than in control subjects (P < 0.001). FEV1 was lower in ADM than in other groups (NADM, athletes control, and nonathletes control, P < 0.001). CONCLUSIONS: Aerobic capacity in subjects with type 1 diabetes with programmed exercise is similar to the capacity of normal athletes despite lower anaerobic threshold and FEV1.

Algorithm for the treatment of type 2 diabetes: a position statement of Brazilian Diabetes Society.

The Brazilian Diabetes Society is starting an innovative project of quantitative assessment of medical arguments of and implementing a new way of elaborating SBD Position Statements. The final aim of this particular project is to propose a new Brazilian algorithm for the treatment of type 2 diabetes, based on the opinions of endocrinologists surveyed from a poll conducted on the Brazilian Diabetes Society website regarding the latest algorithm proposed by American Diabetes Association /European Association for the Study of Diabetes, published in January 2009.An additional source used, as a basis for the new algorithm, was to assess the acceptability of controversial arguments published in international literature, through a panel of renowned Brazilian specialists. Thirty controversial arguments in diabetes have been selected with their respective references, where each argument was assessed and scored according to its acceptability level and personal conviction of each member of the evaluation panel.This methodology was adapted using a similar approach to the one adopted in the recent position statement by the American College of Cardiology on coronary revascularization, of which not only cardiologists took part, but also specialists of other related areas.

Conducting cost-effectiveness analyses of type 2 diabetes in low- and middle-income countries: can locally generated observational study data overcome methodological limitations?

In low- and middle-income countries, the high personal and economic burden of type 2 diabetes is further compounded by inadequate resources for diabetes care when compared with high-income countries. Health technology assessments (HTAs) aim to inform policy decision makers in their efforts to achieve more effective allocation of resources by providing evidence-based input on new technologies. Within the hierarchy of evidence, randomized controlled trials (RCTs) remain the 'gold standard' used to inform HTAs, but are limited by poor external validity (ie, generalizability to real-world populations). Unlike RCTs, observational studies are able to enrol broader patient populations, but their design renders such studies vulnerable to confounding factors and selection bias. However, it is increasingly recognized that observational studies can complement RCTs by supporting and extending efficacy findings from RCTs to real-world clinical practice, particularly across geographical populations. They can also provide locally relevant baseline and disease natural history data to populate health economic models. Thus, observational data are likely to be of considerable informative value to policy makers in developing countries reaching decisions on diabetes care within an environment of scarce resources.