Effects of Tirzepatide Versus Basal Insulins in People With Type 2 Diabetes and Different Baseline Glycemic Patterns: Post Hoc Analyses of the SURPASS-3 and SURPASS-4 Trials.

OBJECTIVE: This post hoc analysis assessed change from baseline to week 52 in glycemic parameters for tirzepatide (5, 10, 15 mg) versus insulin degludec (SURPASS-3 trial) and glargine (SURPASS-4 trial) in people with type 2 diabetes and different baseline glycemic patterns, based on fasting serum glucose (FSG) and postprandial glucose (PPG) values. RESEARCH DESIGN AND METHODS: Participant subgroups with low FSG/low PPG, low FSG/high PPG, high FSG/low PPG, and high FSG/high PPG were defined according to the median values of these measures. RESULTS: All tirzepatide doses and basal insulins were associated with decreased HbA1c, FSG, and PPG values from baseline to week 52 in all subgroups (P < 0.05). Within each subgroup, HbA1c and PPG decreases were greater with tirzepatide than insulin (P < 0.05). FSG decreases were generally similar. There were no differential treatment effects by FSG/PPG subgroup. CONCLUSIONS: In this post hoc analysis, tirzepatide was associated with superior glycemic control compared with insulin, irrespective of baseline glycemic pattern.

Achieving Normoglycemia With Tirzepatide: Analysis of SURPASS 1-4 Trials.

OBJECTIVE: Tirzepatide is a novel single-molecule glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor agonist, which demonstrated unprecedented improvements in glycemic control and body weight reduction, in the SURPASS phase 3 program. In this exploratory analysis, we aimed to characterize tirzepatide-treated participants who achieved HbA1c <5.7% and evaluate changes in clinical markers associated with long-term cardiometabolic health. RESEARCH DESIGN AND METHODS: Baseline characteristics and change from baseline to week 40 for several efficacy and safety parameters were analyzed according to HbA1c attainment category (<5.7%, 5.7-6.5%, and >6.5%) using descriptive statistics in participants taking ≥75% of treatment doses, without rescue medication, in the SURPASS 1-4 trials (N = 3,229). Logistic regression models with tirzepatide doses adjusted as a covariate were used to obtain odds ratios and assess the impact of patient characteristics achieving an HbA1c <5.7%. RESULTS: Tirzepatide-treated participants who achieved HbA1c <5.7% were slightly younger, with a shorter duration of diabetes and lower HbA1c value at baseline compared with those who did not achieve HbA1c <5.7%. In addition, they showed greater improvements in HbA1c, body weight, waist circumference, blood pressure, liver enzymes, and lipid parameters without increasing hypoglycemia risk. CONCLUSIONS: Normoglycemia was unprecedently achieved in a significant proportion of participants in the SURPASS clinical program, without increasing hypoglycemia risk, and was associated with an overall improvement in metabolic health.

Practical Application of Continuous Glucose Monitoring in Clinical Practice: Case Studies.

The prevalence of diabetes continues to rise exponentially and contributes significantly to morbidity, mortality, and health care resource utilization. Individuals with diabetes have adopted continuous glucose monitoring (CGM) as their preferred method for glucose measurement. Primary care clinicians should become proficient in utilizing this technology in their practices. This case-based article provides practical guidance in CGM interpretation allowing patients to become successful partners in diabetes self-management. Our approach to data interpretation and shared decision-making is applicable to all current CGM systems.

Real-world performance of the MiniMed 780G advanced hybrid closed loop system in Latin America: Substantial improvement in glycaemic control with each technology iteration of the MiniMed automated insulin delivery system.

AIM: We studied real-world performance of MiniMed (MM) 780G system users from Argentina, Brazil, Colombia and Chile (geographical analysis), and the effect of each technology iteration of the MM system on glycaemic control (technology iteration analysis). MATERIALS AND METHODS: CareLink data from August 2020 to September 2022 were extracted. Endpoints included continuous glucose monitoring metrics. For the geographical analysis, aggregated endpoints for MM780G system users were calculated. For the technology iteration analysis, MM780G system user outcomes were compared with outcomes when the same individuals were still using the MM640G or MM670G system. RESULTS: On average, 1025 MM780G system users from the geographical analysis were followed for 136 (SD 135) days, spent 91.5 (14.3)% in advanced hybrid closed loop, showed a glucose management indicator (GMI) of 6.7 (0.3)%, a time in range between 70 and 180 mg/dl (TIR) of 76.5 (9.0)%, and a time below range 70 mg/dl (TBR) of 2.7 (2.1)%. The percentage of users reaching targets of GMI <7%, TIR >70% and TBR <4% was 80.8%, 78.1% and 80.1%, respectively. The technology iteration analysis on users transitioning from MM640G to MM780G system (N = 381) showed 0.4% decrease in GMI (7.1% to 6.7%, p < .0001), 10.7% increase in TIR (65.9% to 76.6%, p < .0001), while TBR remained. The percentage of insulin delivered automatically increased as well (47.5%-57.7%, p < .0001). Users transitioning from MM670G system (N = 78) showed a similar but less pronounced pattern. CONCLUSIONS: Real-world Latin American MM780G users on average showed good glucose control, achieving international targets. Glycaemic control increased with every technology iteration of the MM system, providing more automation each time.

Efficacy and safety of ultra-rapid lispro versus lispro in children and adolescents with type 1 diabetes: The PRONTO-Peds trial.

AIMS: To evaluate the efficacy and safety of ultra-rapid lispro (URLi) versus lispro in a paediatric population with type 1 diabetes (T1D) in a Phase 3, treat-to-target study. MATERIALS AND METHODS: After a 4-week lead-in to optimize basal insulin, participants were randomized to double-blind URLi (n = 280) or lispro (n = 298) injected 0 to 2 minutes prior to meals (mealtime), or open-label URLi (n = 138) injected up to 20 minutes after start of meals (postmeal). Participants remained on pre-study basal insulin (degludec, detemir or glargine). The primary endpoint was glycated haemoglobin (HbA1c) change from baseline after 26 weeks (noninferiority margin 4.4 mmol/mol [0.4%]). RESULTS: Both mealtime and postmeal URLi demonstrated noninferiority to lispro for HbA1c: estimated treatment difference (ETD) for mealtime URLi -0.23 mmol/mol (95% confidence interval [CI] -1.84, 1.39) and postmeal URLi -0.17 mmol/mol (95% CI -2.15, 1.81). Mealtime URLi reduced 1-hour postprandial glucose (PPG) daily mean (P = 0.001) and premeal to 1 hour postmeal PPG excursion daily mean (P < 0.001) versus lispro. The rate and incidence of severe, nocturnal or documented hypoglycaemia (<3.0 mmol/L [54 mg/dL]) were similar for all treatments. With mealtime URLi versus lispro, the rate of postdose hypoglycaemia (<3.0 mmol/L) was higher at ≤2 hours (P = 0.034). The incidence of treatment-emergent adverse events was similar for all treatments. More participants reported an injection site reaction with mealtime URLi (7.9%) versus postmeal URLi (2.9%) and lispro (2.7%). CONCLUSIONS: In children and adolescents with T1D, URLi demonstrated good glycaemic control, and noninferiority to lispro in HbA1c change for mealtime and postmeal URLi. When dosed at the beginning of meals, URLi reduced 1-hour PPG and PPG excursions versus lispro.

Análise da estrutura das Unidades Básicas de Saúde do Brasil para a realização de ações do telessaúde / Analysis of the structure of basic health units in Brazil to conduct telehealth actions

O telessaúde é a utilização das Tecnologias de Informação e Comunicação (TIC) nas atividades relacionadas à saúde desenvolvidas à distância entre profissionais e/ou pacientes. Para que as ações do telessaúde proporcionem serviços de saúde resolutivos é fundamental que os ambientes de trabalho tenham infraestrutura disponível em relação as TIC. O objetivo principal foi comparar a infraestrutura de TIC, que favorece o desenvolvimento de ações de telessaúde, nas Unidades Básicas de Saúde (UBS) participantes do Programa Nacional de Melhoria do Acesso e da Qualidade da Atenção Básica (PMAQ-AB) no Brasil e regiões brasileiras; além de organizar um curso de formação profissional para os profissionais de saúde bucal de Ouro Branco, Minas Gerais (MG). Este estudo longitudinal utilizou dados secundários do segundo e terceiro ciclos do PMAQ-AB, realizados respectivamente nos anos de 2013/2014 e 2017/2018. Apenas as UBS que participaram de ambos os ciclos foram incluídas e pareadas pelo Cadastro Nacional de Estabelecimentos de Saúde (CNES). A amostra final foi de 22.021 UBS. As variáveis selecionadas para o estudo foram obtidas do Módulo I - Observação em Unidades Básicas de Saúde, na subdimensão - Equipamentos de tecnologia da informação e telessaúde. Participaram apenas as variáveis comuns aos dois ciclos representadas por computador, câmera, caixa de som, microfone, impressora, televisão e internet suficiente. A presença de cada equipamento de TIC atribuiu uma pontuação a cada UBS, sendo a pontuação final a soma do número de equipamentos identificados no serviço de saúde (de 0 a 7 pontos). Os dados foram analisados descritivamente e por meio do teste de Wilcoxon (p≤0,05) para comparar os escores das UBS no Brasil e nas regiões brasileiras, utilizando o programa SPSS, v. 25.0. Houve um aumento no número de UBS para todos os equipamentos de TIC analisados e aumento significativo da mediana de equipamentos de TIC do segundo para o terceiro ciclo no Brasil (3;4) e nas regiões brasileiras (p<0,001): Sul (4,5;5), Centro-Oeste (3,5;4), Norte (2;3) e Nordeste (1;3). Apenas a região Sudeste manteve o valor mediano de equipamentos (4) em ambos os ciclos. As regiões Sul, Sudeste e Centro-Oeste apresentaram as maiores medianas de pontuação em ambos os ciclos, mostrando melhores estruturas de TIC. A disponibilidade de equipamentos de TIC para ações do telessaúde nas UBS aumentou ao longo dos ciclos do PMAQ-AB com diferenças entre as regiões brasileiras. Em relação ao produto técnico foi realizado um Curso de Formação Profissional para as equipes de saúde bucal da Atenção Primária à Saúde, do Centro de Especialidades Odontológicas e da coordenação de saúde bucal da Prefeitura Municipal de Ouro Branco/ MG. O curso foi ministrado em dois dias, com uma carga horária de 3 horas/dia. O conteúdo teórico abordou normatizações, vantagens e modalidades de ações do telessaúde, além de um momento prático para que os participantes executassem uma simulação de um telemonitoramento. Durante a realização deste produto foram criados 5 roteiros de telemonitoramento que juntos podem contribuir para melhoria da qualidade de atenção na prestação de serviços do telessaúde à população do município.

Telehealth is the use of Information and Communication Technologies (ICT) in healthrelated activities carried out remotely among professionals and patients. For telehealth actions to provide resolutive health services, it is essential that work environments have ICT infrastructure available. The main objective was to compare the ICT infrastructure that favors the development of telehealth actions in the Basic Health Units (BHU) participating in the National Program for Improving Access and Quality in Primary Care (PMAQ-AB) in Brazil and Brazilian regions; in addition to organizing a professional training course for oral health professionals in Ouro Branco, Minas Gerais (MG). This longitudinal study used secondary data from the second and third cycles of PMAQ-AB, carried out in 2013/2014 and 2017/2018 respectively. Only BHU that participated in both cycles were included and matched by the National Register of Health Establishments. The final sample consisted of 22,021 BHU. The variables selected for the study were obtained from module I - Observation in Basic Health Units in the subdimension - Information technology and telehealth equipment. Only the variables common to both cycles, represented by computer, camera, speaker, microphone, printer, television and sufficient internet, took part. The presence of each piece of ICT equipment gave each BHU a score, with the final score being the sum of the number of pieces of equipment identified in the health service (from 0 to 7 points). The data was analyzed descriptively and using the Wilcoxon test (p≤0.05) to compare the scores of the BHUs in Brazil and in the Brazilian regions, using the SPSS program, v. 25.0. There was an increase in the number of BHU for all the ICT equipment analyzed and a significant increase in the median number of ICT equipment from the second to the third cycle in Brazil (3;4) and in the Brazilian regions (p<0.001): South (4.5;5), Midwest(3.5;4), North (2;3) and Northeast (1;3). Only the Southeast maintained the median value of equipment (4) in both cycles. The South, Southeast and CentralWest regions had the highest median scores in both cycles, showing better ICT structures. The availability of ICT equipment for telehealth actions in the UBS increased over the PMAQ-AB cycles, with differences between the Brazilian regions. With regard to the technical product, a Professional Training Course was held for the oral health teams of the Primary Health Care, the Dental Specialties Center and the oral health coordination of the Ouro Branco/MG city hall. The course was given over two days, with a workload of 3 hours/day. The theoretical content covered standards, advantages and types of telehealth actions, as well as a practical moment for participants to carry out a simulation of telemonitoring. During the course of this product, 5 telemonitoring scripts were created, which together can contribute to improving the quality of care in the provision of telehealth services to the municipality's population.

GLP-1 Agonist to Treat Obesity and Prevent Cardiovascular Disease: What Have We Achieved so Far?

PURPOSE OF REVIEW: To discuss evidence supporting the use of glucagon-like peptide 1 receptor agonists (GLP-1RA) to treat obesity and their role as a cardioprotective drug. Obesity is not just a hypertrophy of the adipose tissue because it may become dysfunctional and inflamed resulting in increased insulin resistance. Being overweight is associated with increased incidence of cardiovascular events and weight loss achieved through lifestyle changes lowers risk factors, but has no clear effect on cardiovascular outcomes. In contrast, treating obesity with GLP-1RA decreases cardiovascular risk and the possible mechanisms of cardioprotection achieved by this class of drugs are discussed. GLP-1RA were initially developed to treat type 2 diabetes patients, in whom the effects upon glycemia and, moreover, weight loss, especially with long-acting GLP-1RA, were evident. However, cardiovascular safety trials in type 2 diabetes patients, the majority presenting cardiovascular disease and excess weight, showed that GLP-1 receptor agonists were indeed capable of decreasing cardiovascular risk. RECENT FINDINGS: Type 2 diabetes treatment with GLP-1RA liraglutide and semaglutide paved way to a ground-breaking therapy specific for obesity, as shown with the SCALE 3 mg/day liraglutide program and the STEP 2.4 mg/week semaglutide program. A novel molecule with superior performance is tirzepatide, a GLP-1 and GIP (Gastric Inhibitory Peptide) receptor agonist and recent results from the SURPASS and SURMOUNT programs are briefly described. Liraglutide was approved without a CVOT (Cardiovascular Outcome Trial) because authorities accepted the results from the LEADER study, designed for superiority. The SELECT study with semaglutide will report results only in 2023 and tirzepatide is being tested in patients with diabetes in the SURPASS-CVOT. Clinical studies highlight that GLP-1RA to treat obesity, alongside their concomitant cardioprotective effects, have become a hallmark in clinical science.

Oral GLP-1 analogue: perspectives and impact on atherosclerosis in type 2 diabetic patients.

Cardiovascular events related to atherosclerosis are responsible for high morbidity and mortality among patients with type 2 diabetes. Improvement in care, especially in early stages, is crucial. Oral semaglutide, a glucagon-like peptide 1 analogue, controls blood glucose and results in significant body weight loss in patients with type 2 diabetes. Beyond these well-known effects, an interesting aspect of this drug is its antiatherogenic activity, which should be further explored in clinical practice. This paper reviews the evidence related to oral semaglutide decreasing cardiovascular risk in patients with type 2 diabetes, focusing on the drug's antiatherosclerotic properties. The glucagon-like peptide 1 analogue restores endothelial dysfunction, induces vasodilatation, and reduces plasma lipids. Oral semaglutide showed cardiovascular safety profile, with significant reduced risk of death from cardiovascular events. Based on current data, clinicians should consider oral semaglutide for type 2 diabetes management.

Decentralized COVID-19 measures in Brazil were ineffective to protect people with diabetes.

BACKGROUND AND AIMS: COVID-19 severity and mortality are elevated in individuals with diabetes. During the pandemic, interventions recommended globally for people with diabetes were to keep blood glucose on target whilst staying at home to curb the spread of the virus. In Brazil, similar measures were proposed. The aim of our observational study was to assess whether these measures achieved their objectives. METHODS: An anonymous and untraceable survey was shared from April 22nd to May 4th. States with more than 30 respondents were included in the analysis and Fisher's exact test was performed to identify associations, with p < 0.05 considered significant. RESULTS: Type 1 diabetes and female participants were prevalent, 60.76% and 76.12% respectively. 10 out of 26 states were included, in addition to the Federal District (1562 responses). Only in three states (Bahia, Goiás and Pernambuco) less than 50% of the respondents experienced higher glycemia or higher variability during the pandemic. Goiás state, where almost half of the respondents (49.12%) have private insurance, presented the highest percentage of individuals receiving medicines for three months (35.48%) and one of the lowest percentages of blood glucose deterioration (47.17%). In the large states of Minas Gerais, Rio de Janeiro and São Paulo, consultations and/or lab exams were postponed by 37.14%, 34.33% and 40.88%, respectively. CONCLUSIONS: The decentralized measures implemented by states in Brazil left most people with diabetes unprotected. Many were forced to venture outside to collect or to purchase their medical supplies monthly and reported increased glycemic levels and/or variability.

Effect of a Nutritional Support System (Diet and Supplements) for Improving Gross Motor Function in Cerebral Palsy: An Exploratory Randomized Controlled Clinical Trial.

BACKGROUND: Most patients with cerebral palsy (CP) do not respond to physical therapy due to deterioration in their nutritional status, secondary to gastrointestinal disorders and the catabolic state of the disease itself. However, basic treatments only contemplate the energy requirements and do not consider supplementation with glutamine, zinc, selenium, colecalciferol, spirulina, omega 3 or even vegetal proteins. OBJECTIVE: In this study, we determined the effect of using a nutritional support system (NSS): diet and supplements, on the gross motor function in children with CP with spastic diparesic and Gross Motor Function Classification System III (GMFCS III). METHODS: An exploratory study was performed. Thirty patients (from 4 to 12 years old) were randomly assigned to: (1) dietary surveillance (FG), (2) deworming and WHO diet (CG), or (3) deworming and the NSS (IG). Gross motor function was evaluated using the gross motor function measure (GMFM) scale. RESULTS: The IG-treated group presented a significant improvement in standing and walking parameters analyzed in the GMFM compared with FG and CG groups. Fifty percent of the IG-treated patients managed to walk, while in the other groups, no patients were able to walk. CONCLUSIONS: The NSS used in the present work improves gross motor function and promotes walking in patients with CP.

The impact of COVID-19 on people with diabetes in Brazil.

The present study aims at identifying main barriers faced by people living with diabetes in Brazil during the COVID-19 pandemic. METHODS: In a convenience sampling study, data were collected from 1701 individuals, aged 18 or above; 75.54% female participants; 60.73% T1D and 30.75% T2D, between April 22nd and May 4th, using an anonymous and untraceable survey containing 20 multiple choice questions (socio-demographic; health status and habits of life during COVID-19 pandemic). Relationship between variables was established using the multiple correspondence analysis technique. RESULTS: 95.1% of respondents reduced their frequency of going outside of their homes; among those who monitored blood glucose at home during the pandemic (91.5%), the majority (59.4%) experienced an increase, a decrease or a higher variability in glucose levels; 38.4% postponed their medical appointments and/or routine examinations; and 59.5% reduced their physical activity. T1D, the youngest group, was more susceptible to presenting COVID-19 symptoms despite not being testing; whilst the T2D group had higher frequency of comorbidities that are additional risk factors for COVID-19 severity. CONCLUSIONS: This study provides a first hand revelation of the severity of COVID-19 on individuals with diabetes in Brazil. Their habits were altered, which impacted their glycemia, potentially increasing the risk of poor outcomes and mortality if infected by SARS-CoV-2, and of acute and chronic diabetes complications.

Efficacy and Safety of Insulin Glargine 300 Units/mL (Gla-300) Versus Insulin Glargine 100 Units/mL (Gla-100) in Children and Adolescents (6-17 years) With Type 1 Diabetes: Results of the EDITION JUNIOR Randomized Controlled Trial.

OBJECTIVE: To compare efficacy and safety of insulin glargine 300 units/mL (Gla-300) and 100 units/mL (Gla-100) in children and adolescents (6-17 years old) with type 1 diabetes. RESEARCH DESIGN AND METHODS: EDITION JUNIOR was a noninferiority, international, open-label, two-arm, parallel-group, phase 3b trial. Participants were randomized 1:1 to Gla-300 or Gla-100, titrated to achieve fasting self-monitored plasma glucose levels of 90-130 mg/dL (5.0-7.2 mmol/L), with continuation of prior prandial insulin. The primary end point was change in HbA1c from baseline to week 26. Other assessments included change in fasting plasma glucose (FPG), hypoglycemia, hyperglycemia with ketosis, and adverse events. RESULTS: In 463 randomized participants (Gla-300, n = 233; Gla-100, n = 230), comparable least squares (LS) mean (SE) reductions in HbA1c were observed from baseline to week 26 (-0.40% [0.06%] for both groups), with LS mean between-group difference of 0.004% (95% CI -0.17 to 0.18), confirming noninferiority at the prespecified 0.3% (3.3 mmol/mol) margin. Mean FPG change from baseline to week 26 was also similar between groups. During the 6-month treatment period, incidence and event rates of severe or documented (≤70 mg/dL [≤3.9 mmol/L]) hypoglycemia were similar between groups. Incidence of severe hypoglycemia was 6.0% with Gla-300 and 8.8% with Gla-100 (relative risk 0.68 [95% CI 0.35-1.30]). Incidence of any hyperglycemia with ketosis was 6.4% with Gla-300 and 11.8% with Gla-100. CONCLUSIONS: Gla-300 provided similar glycemic control and safety profiles to Gla-100 in children and adolescents with type 1 diabetes, indicating that Gla-300 is a suitable therapeutic option in this population.

Time in range: a new parameter to evaluate blood glucose control in patients with diabetes.

The International Consensus in Time in Range (TIR) was recently released and defined the concept of the time spent in the target range between 70 and 180 mg/dL while reducing time in hypoglycemia, for patients using Continuous Glucose Monitoring (CGM). TIR was validated as an outcome measures for clinical Trials complementing other components of glycemic control like Blood glucose and HbA1c. The challenge is to implement this practice more widely in countries with a limited health public and private budget as it occurs in Brazil. Could CGM be used intermittently? Could self-monitoring blood glucose obtained at different times of the day, with the amount of data high enough be used? More studies should be done, especially cost-effective studies to help understand the possibility of having sensors and include TIR evaluation in clinical practice nationwide.

Real-world outcomes of treatment with insulin glargine 300 U/mL versus standard-of-care in people with uncontrolled type 2 diabetes mellitus.

Objective: To compare real-world outcomes with newer (insulin glargine 300 U/mL; Gla-300) versus standard of care (SoC) basal insulins (BIs) in the REACH (insulin-naïve; NCT02967224) and REGAIN (basal insulin-treated; NCT02967211) studies in participants with uncontrolled type 2 diabetes (T2DM) in Europe and Brazil.Methods: In these open-label, parallel-group, pragmatic studies, patients (HbA1c > 7.0%) were randomized to Gla-300 or SoC BI for a 6-month treatment period (to demonstrate non-inferiority of Gla-300 vs SoC BIs for HbA1c change [non-inferiority margin 0.3%]) and a 6-month extension period (continuing with their assigned treatment). Insulin titration/other medication changes were at investigator/patient discretion post-randomization.Results: Overall, 703 patients were randomized to treatment in REACH (Gla-300, n = 352; SoC, n = 351) and 609 (Gla-300, n = 305, SoC, n = 304) in REGAIN. The primary outcome, non-inferiority of Gla-300 versus SoC for HbA1c change from baseline to month 6, was met in REACH (least squares [LS] mean difference 0.12% [95% CI -0.046 to 0.281]) but not REGAIN (LS mean difference 0.17% [0.015-0.329]); no between-treatment difference in HbA1c change was shown after 12 months in either study. BI dose increased minimally from baseline to 12 months in REACH (Gla-300, +0.17 U/kg; SoC, +0.15 U/kg) and REGAIN (Gla-300, +0.11 U/kg; SoC, +0.07 U/kg). Hypoglycemia incidence was low and similar between treatment arms in both studies.Conclusions: In both REACH and REGAIN, no differences in glycemic control or hypoglycemia outcomes with Gla-300 versus SoC BIs were seen over 12 months. However, the suboptimal insulin titration in REACH and REGAIN limits comparisons of outcomes between treatment arms and suggests that more titration instruction/support may be required for patients to fully derive the benefits from newer basal insulin formulations.

Basal insulin persistence in Brazilian participants with T2DM.

OBJECTIVE: Real-world effectiveness of basal insulin therapy is affected by poor treatment persistence, often occurring soon after initiation. This analysis is part of an international cross-sectional study conducted in T2DM patients and is intended to describe the reasons behind non-persistence to insulin therapy in Brasil. METHODS: Responders to an online survey in seven countries were classified as continuers (no gap of ≥7 days), interrupters (interrupted therapy for ≥7 days within first 6 months, then restarted), and discontinuers (terminated therapy for ≥7 days within first 6 months, and did not start it again before the survey). We present the results from the Brazilian cohort. RESULTS: Of 942 global respondents, 156 were from Brasil, with a mean age of 34 years and a mean of 5.8 years since T2DM diagnosis. Reasons contributing to insulin continuation (n=50) were improved glycemic control (82%) and improved physical feeling (50%). Common reasons for interruption (n=51) or discontinuation (n=55) were, respectively, weight gain (47.1%, 43.6%), hypoglycemia (45.1%, 38.2%), and pain from injections (39.2%, 49.1%). However, not all patients who reported weight gain and hypoglycemia as a reason for interruption or discontinuation experienced these: 16/24 (66.7%) and 22/24 (91.7%) participants had weight gain, and 13/23 (56.5%) and 15/21 (71.4%) had hypoglycemia, respectively. The most important reason for possible re-initiation for interrupters and discontinuers, respectively, was persuasion by the physician/HCP (80.4%, 72.7%). CONCLUSION: The benefits of basal insulin therapy motivated continuers to persist with the treatment; experienced or anticipated side effects contributed to interruption and discontinuation. Physician and patient training is key in the treatment of diabetes.

Basal insulin persistence in Brazilian participants with T2DM

SUMMARY OBJECTIVE Real-world effectiveness of basal insulin therapy is affected by poor treatment persistence, often occurring soon after initiation. This analysis is part of an international cross-sectional study conducted in T2DM patients and is intended to describe the reasons behind non-persistence to insulin therapy in Brasil. METHODS Responders to an online survey in seven countries were classified as continuers (no gap of ≥7 days), interrupters (interrupted therapy for ≥7 days within first 6 months, then restarted), and discontinuers (terminated therapy for ≥7 days within first 6 months, and did not start it again before the survey). We present the results from the Brazilian cohort. RESULTS Of 942 global respondents, 156 were from Brasil, with a mean age of 34 years and a mean of 5.8 years since T2DM diagnosis. Reasons contributing to insulin continuation (n=50) were improved glycemic control (82%) and improved physical feeling (50%). Common reasons for interruption (n=51) or discontinuation (n=55) were, respectively, weight gain (47.1%, 43.6%), hypoglycemia (45.1%, 38.2%), and pain from injections (39.2%, 49.1%). However, not all patients who reported weight gain and hypoglycemia as a reason for interruption or discontinuation experienced these: 16/24 (66.7%) and 22/24 (91.7%) participants had weight gain, and 13/23 (56.5%) and 15/21 (71.4%) had hypoglycemia, respectively. The most important reason for possible re-initiation for interrupters and discontinuers, respectively, was persuasion by the physician/HCP (80.4%, 72.7%). CONCLUSION The benefits of basal insulin therapy motivated continuers to persist with the treatment; experienced or anticipated side effects contributed to interruption and discontinuation. Physician and patient training is key in the treatment of diabetes.

RESUMO OBJETIVO Dados de vida real sobre como a eficácia da terapia com insulina é afetada pela baixa persistência ao tratamento que ocorre logo após o início da terapia. Esta análise é a parte brasileira de um estudo transversal internacional conduzido em pacientes com DM2 que teve como objetivo descrever as razões relacionadas à não persistência ao tratamento com insulina. METODOLOGIA O estudo realizado em sete países por meio de questionários on-line classificou como pacientes continuadores (aqueles que não apresentaram intervalo ≥7 dias sem uso da insulina), interrompedores (interromperam a terapia por ≥7 dias nos primeiros seis meses de uso, depois recomeçaram) e descontinuadores (interromperam a terapia por ≥7 dias nos primeiros seis meses de uso e não retornaram). Nesta análise descrevemos os dados da coorte brasileira. RESULTADOS Dos 942 pacientes incluídos, 156 eram do Brasil, com idade média de 34 anos e média de seis anos desde o diagnóstico de DM2. Razões que contribuíram para o uso contínuo da insulina (n=50) foram a melhora do controle glicêmico (82%) e a melhora no estado geral (50%). Razões para a interrupção (n=51) ou para a descontinuação (n=55) foram, respectivamente, ganho de peso (41,7%, 43,6%), hipoglicemia (45,1%, 38,2%) e dor à aplicação (39,2%, 49,1%). Entretanto, nem todos os pacientes que reportaram ganho de peso e hipoglicemia como possível razão para interrupção ou descontinuação realmente apresentaram esses eventos: 16/24 (66,7%) e 22/24 (91,4%) dos participantes apresentaram ganho de peso e 13/23 (56,6%) e 15/21 (71,4%) apresentaram hipoglicemia, respectivamente. A razão mais importante para o possível recomeço entre os interrompedores e descontinuadores foi a persuasão de médicos/profissionais de saúde (80,4% e 72,7%, respectivamente). CONCLUSÕES Os benefícios do tratamento com insulina basal motivaram continuadores a persistir com a terapia; a experiência ou a antecipação de eventos adversos contribuíram para a interrupção e descontinuação. O treinamento de médicos e pacientes é um dos pilares fundamentais do tratamento do diabetes.

Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.

BACKGROUND: Establishing cardiovascular safety of new therapies for type 2 diabetes is important. Safety data are available for the subcutaneous form of the glucagon-like peptide-1 receptor agonist semaglutide but are needed for oral semaglutide. METHODS: We assessed cardiovascular outcomes of once-daily oral semaglutide in an event-driven, randomized, double-blind, placebo-controlled trial involving patients at high cardiovascular risk (age of ≥50 years with established cardiovascular or chronic kidney disease, or age of ≥60 years with cardiovascular risk factors only). The primary outcome in a time-to-event analysis was the first occurrence of a major adverse cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke). The trial was designed to rule out 80% excess cardiovascular risk as compared with placebo (noninferiority margin of 1.8 for the upper boundary of the 95% confidence interval for the hazard ratio for the primary outcome). RESULTS: A total of 3183 patients were randomly assigned to receive oral semaglutide or placebo. The mean age of the patients was 66 years; 2695 patients (84.7%) were 50 years of age or older and had cardiovascular or chronic kidney disease. The median time in the trial was 15.9 months. Major adverse cardiovascular events occurred in 61 of 1591 patients (3.8%) in the oral semaglutide group and 76 of 1592 (4.8%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.57 to 1.11; P<0.001 for noninferiority). Results for components of the primary outcome were as follows: death from cardiovascular causes, 15 of 1591 patients (0.9%) in the oral semaglutide group and 30 of 1592 (1.9%) in the placebo group (hazard ratio, 0.49; 95% CI, 0.27 to 0.92); nonfatal myocardial infarction, 37 of 1591 patients (2.3%) and 31 of 1592 (1.9%), respectively (hazard ratio, 1.18; 95% CI, 0.73 to 1.90); and nonfatal stroke, 12 of 1591 patients (0.8%) and 16 of 1592 (1.0%), respectively (hazard ratio, 0.74; 95% CI, 0.35 to 1.57). Death from any cause occurred in 23 of 1591 patients (1.4%) in the oral semaglutide group and 45 of 1592 (2.8%) in the placebo group (hazard ratio, 0.51; 95% CI, 0.31 to 0.84). Gastrointestinal adverse events leading to discontinuation of oral semaglutide or placebo were more common with oral semaglutide. CONCLUSIONS: In this trial involving patients with type 2 diabetes, the cardiovascular risk profile of oral semaglutide was not inferior to that of placebo. (Funded by Novo Nordisk; PIONEER 6 ClinicalTrials.gov number, NCT02692716.).

Improving the school experience of children with diabetes: Evaluation of the KiDS project.

BACKGROUND: The International Diabetes Federation (IDF) launched the Kids and Diabetes in School (KiDS) project in collaboration with the International Society for Paediatric and Adolescent Diabetes (ISPAD) and Sanofi Diabetes to inform and teach school staff, children and parents on the management of diabetes in school. Brazil and India were chosen as pilot countries. METHODS: The evaluation was conducted using a qualitative methodology using semi-structured face to face in-depth interviews. Five out of fifteen schools were selected, where teachers and parents of children with and without diabetes were interviewed. Interviews took place one and three months after the implementation of KiDS. FINDINGS: Diabetes knowledge among the school staff and parents of children without diabetes was very limited prior to the KiDS Project in both countries. After introducing the KiDS information pack both groups mentioned increased knowledge on the management of diabetes. This was reflected through healthier food choices at school and the encouragement of physical activities. Increased awareness and understanding in the school staff were observed by parents of children with diabetes. INTERPRETATION: The KiDS project received positive feedback on the educational materials. The pack was deemed informative, interesting and engaging, creating increased awareness and understanding among school staff, parents and children. The project has created a demand for diabetes intervention in schools. The pack has been translated into fourteen languages and was downloaded over 17,000 times by November 2018.

The rate of hyperglycemia and ketosis with insulin degludec-based treatment compared with insulin detemir in pediatric patients with type 1 diabetes: An analysis of data from two randomized trials.

BACKGROUND: Historically, data on the rate of hyperglycemia and ketosis have not been collected in clinical trials. However, it is clinically important to assess the rate of these events in children with type 1 diabetes (T1D). This question was addressed in two pediatric trials using insulin degludec (degludec). OBJECTIVE: To assess the rate of hyperglycemia and ketosis in two-phase 3b trials investigating degludec (Study 1) and degludec with insulin aspart (IDegAsp [Study 2]) vs insulin detemir (IDet). SUBJECTS: Patients (aged 1-17 years inclusive) with T1D treated with insulin for ≥3 months. METHODS: Study 1: patients were randomized to degludec once daily (OD) or IDet OD/twice daily (BID) for 26 weeks, followed by a 26-week extension phase. Study 2: patients were randomized to IDegAsp OD or IDet OD/BID for 16 weeks. Bolus mealtime IAsp was included in both studies. In Study 1, hyperglycemia was recorded if plasma glucose (PG) was >11.1 mmol/L, with ketone measurement required with significant hyperglycemia (>14.0 mmol/L). In Study 2, hyperglycemia was recorded with PG >14.0 mmol/L where the subject looked/felt ill, with ketone measurement also required in these hyperglycemic patients. In this post hoc analysis, the hyperglycemia threshold was 14.0 mmol/L for uniformity. RESULTS: Despite similar rates of hyperglycemia with degludec/IDegAsp compared with IDet, the rates of ketosis were lower with degludec/IDegAsp. CONCLUSIONS: These trials, the first to systematically collect data on ketosis in pediatric patients with T1D, demonstrate the potential of degludec/IDegAsp to reduce rates of metabolic decompensation, compared with IDet.

Cardiovascular safety of oral semaglutide in patients with type 2 diabetes: Rationale, design and patient baseline characteristics for the PIONEER 6 trial.

AIMS: To assess the cardiovascular (CV) safety of oral semaglutide, the first tablet formulation of a glucagon-like peptide-1 receptor agonist. MATERIALS AND METHODS: PIONEER 6 is a multinational, randomized, placebo-controlled, double-blind trial in patients with type 2 diabetes at high risk of CV events (defined as being aged ≥50 years and having established CV disease [CVD] or moderate [stage 3] chronic kidney disease [CKD], or being aged ≥60 years with ≥1 other CV risk factor). Patients were randomized to once-daily oral semaglutide (up to 14 mg) or placebo added to standard of care. The primary composite endpoint is time to first occurrence of CV death or non-fatal myocardial infarction or non-fatal stroke. The primary hypothesis was to exclude an excess in CV risk with oral semaglutide by assessing non-inferiority versus placebo for the primary endpoint (non-inferiority margin of 1.8 for the upper boundary of the 95% confidence interval of the hazard ratio). PIONEER 6 is event-driven, with follow-up continuing until accrual of at least 122 primary outcome events. There is no pre-defined minimal duration. RESULTS: Overall, 3183 patients have been enrolled (mean age 66.1 years, 31.6% females) in 214 sites across 21 countries. At baseline, the mean duration of diabetes was 14.9 years, mean glycated haemoglobin concentration was 66 mmol/mol (8.2%), and 84.6% of patients had established CVD/moderate CKD. CONCLUSIONS: PIONEER 6 will provide evidence regarding the CV safety of oral semaglutide in patients with type 2 diabetes and high CV risk.