Metformin Inhibits ROS/TNF-alpha Axis-Mediated Chronic Kidney Disease Induced by TAA Independent of Leukocyte Infiltration in Association with the Inhibition of Kidney Injury Biomarkers / La Metformina Inhibe la Enfermedad Renal Crónica Mediada por el Eje ROS/TNF-alfa Inducida por TAA Independientemente de la Infiltración de Leucocitos en Asociación con la Inhibición de Biomarcadores de Lesión Renal

SUMMARY: The toxic effects of thioacetamide (TAA) and carbon tetrachloride on the human body are well recognized. In this study, we examined whether TAA intoxication can induce kidney leukocyte infiltration (measured as leukocyte common antigen CD45) associated with the augmentation of the reactive oxygen species (ROS)/tumor necrosis factor-alpha (TNF-α) axis, as well as biomarkers of kidney injury with and without metformin treatment. Rats were either injected with TAA (200 mg/kg; twice a week for 8 weeks) before being sacrificed after 10 weeks (experimental group) or were pre-treated with metformin (200 mg/kg) daily for two weeks prior to TAA injections and continued receiving both agents until the end of the experiment, at week 10 (protective group). Using basic histology staining, immunohistochemistry methods, and blood chemistry analysis, we observed profound kidney tissue injury such as glomerular and tubular damage in the experimental group, which were substantially ameliorated by metformin. Metformin also significantly (p0.05) increase in kidney expression of CD45 positive immunostaining cells. In conclusion, we found that TAA induces kidney injury in association with the augmentation of ROS/TNF-α axis, independent of leukocyte infiltration, which is protected by metformin.

Son bien conocidosos los efectos tóxicos de la tioacetamida (TAA) y el tetracloruro de carbono en el cuerpo humano. En este estudio, examinamos si la intoxicación por TAA puede inducir la infiltración de leucocitos renales (medida como antígeno leucocitario común CD45) asociada con el aumento de las especies reactivas de oxígeno (ROS)/factor de necrosis tumoral-alfa (TNF-α), así como biomarcadores de daño renal con y sin tratamiento con metformina. A las ratas se les inyectó TAA (200 mg/kg; dos veces por semana durante 8 semanas) antes de sacrificarlas a las 10 semanas (grupo experimental) o se les pretrató con metformina (200 mg/kg) diariamente durante dos semanas antes de las inyecciones de TAA y continuaron recibiendo ambos agentes hasta el final del experimento, en la semana 10 (grupo protector). Usando tinción histológica básica, métodos de inmunohistoquímica y análisis químico de la sangre, observamos una lesión profunda del tejido renal, como daño glomerular y tubular en el grupo experimental, que mejoraron sustancialmente con la metformina. La metformina también inhibió significativamente (p0,05) en la expresión renal de células de inmunotinción positivas para CD45. En conclusión, encontramos que el TAA induce la lesión renal en asociación con el aumento del eje ROS/TNF-α, independientemente de la infiltración de leucocitos, que está protegida por metformina.

Efficacy of acupuncture on cardiovascular complications in patients with diabetes mellitus in Korea: A nationwide retrospective cohort / 中西医结合学报

OBJECTIVE@#The main aim of this study is to investigate whether acupuncture could be an effective complementary treatment for reducing the risk of macrovascular complications in diabetic patients currently taking antidiabetic medications using a nationwide population-based database.@*METHODS@#We conducted a retrospective cohort study to assess the efficacy of acupuncture on cardiovascular complications in diabetic patients using data from patients between 40 and 79 years of age, newly diagnosed with diabetes between 2003 and 2006, found in the National Health Insurance Service-National Sample Cohort (NHIS-NSC) in Korea. From the data, we identified 21,232 diabetic patients who were taking antidiabetic medication between 2003 and 2006. The selected patients were divided into two groups-those who received acupuncture at least three times and those who received no acupuncture (non-acupuncture) in the year following their diagnosis of diabetes. After 1:1 propensity score matching (PSM), each group had 3350 patients, and the observation ceased at the occurrence of a major adverse cardiovascular event (MACE), which was defined as either myocardial infarction, stroke, or death due to cardiovascular cause.@*RESULTS@#After PSM, the acupuncture group had a lower incidence of MACE (hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.81-0.94; P = 0.0003) and all-cause mortality (HR: 0.77; 95% CI: 0.70-0.84; P < 0.0001) than the non-acupuncture group; the HRs for stroke-related mortality (HR: 0.75; 95% CI: 0.56-1.00; P = 0.0485), ischemic heart disease mortality (HR: 0.53; 95% CI: 0.34-0.84; P = 0.006) and circulatory system disease mortality (HR: 0.67; 95% CI: 0.55-0.82; P < 0.0001) were lower in the acupuncture group than in the non-acupuncture group in the secondary analysis.@*CONCLUSION@#Our results indicate that diabetic patients receiving acupuncture treatment might have a lower risk of MACE, all-cause mortality and cardiovascular mortality. This population-based retrospective study suggests beneficial effects of acupuncture in preventing macrovascular complications associated with diabetes. These findings call for further prospective cohort or experimental studies on acupuncture treatment for cardiovascular complications of diabetes. Please cite this article as: Jung H, Won T, Kim GY, Jang J, Yeo S, Lim S. Efficacy of acupuncture on cardiovascular complications in patients with diabetes mellitus in Korea: A nationwide retrospective cohort. J Integr Med. 2023; 21(2): 176-183.

Awareness of the diagnosis, treatment, and control of diabetes mellitus in Brazil / Conhecimento do diagnóstico, tratamento e controle do diabetes mellitus no Brasil

ABSTRACT OBJECTIVE To estimate the proportions of awareness, treatment, and control of diabetes mellitus (DM) in the Brazilian adult population. METHOD This is a cross-sectional study, with data from a representative sample of the Brazilian population, taken from the National Health Survey(PNS 2014/2015). Outcomes were defined based on glycated hemoglobin (HbA1c) measurements, self-reported DM diagnosis, and use of hypoglycemic agents or insulin. The proportion of DM awareness, treatment, and control was estimated according to sociodemographic characteristics, health conditions, and access to health services, and their respective 95% confidence intervals. RESULTS DM prevalence in the Brazilian population was of 8.6% (95%CI: 7.8-9.3): 68.2% (95%CI: 63.9-72.3) were aware of their diagnosis, 92.2% (95%CI: 88.6-94.7) of those who were aware were undergoing drug treatments, and, of these, 35.8% (95%CI: 30.5-41.6) had controlled HbA1c levels. The proportions of DM awareness, control, and treatment were lower in men aged 18 to 39 years, individuals with low education, without health insurance, and beneficiaries of the Bolsa Família program. CONCLUSION Approximately one in ten Brazilians has DM. A little more than half of this population is aware of their diagnosis, a condition measured by HbA1c dosage and clinical diagnosis. Among those who know, the vast majority are undergoing drug treatments. However, less than half of these have their HbA1c levels controlled. Worse scenarios were found in subgroups with high social vulnerability.

RESUMO OBJETIVO Estimar as proporções dos indivíduos que têm conhecimento do diagnóstico, tratamento e controle do diabetes mellitus (DM) na população adulta brasileira. MÉTODO Este é um estudo transversal, com dados de amostra representativa da população brasileira, provenientes da Pesquisa Nacional de Saúde (PNS 2014/2015). Os desfechos foram definidos com base na medida de hemoglobina glicada (HbA1c), no diagnóstico autorreferido de DM e no uso de hipoglicemiantes ou de insulina. Estimou-se a proporção do conhecimento, tratamento e controle do DM de acordo com as características sociodemográficas, condição de saúde e de acesso aos serviços de saúde, e seus respectivos intervalos de 95% de confiança (IC95%). RESULTADOS A prevalência de DM na população brasileira foi 8,6% (IC95% 7,8-9,3), 68,2% (IC95% 63,9-72,3) tinham conhecimento do seu diagnóstico, 92,2% (IC95% 88,6-94,7) dos que tinham conhecimento realizam tratamento medicamentoso, e desses, 35,8% (IC95% 30,5-41,6) tinham os níveis de HbA1c controlados. As proporções de conhecimento, controle e tratamento foram menores nos homens, com idade de 18 a 39 anos, indivíduos que possuem baixa escolaridade, sem plano de saúde e beneficiários do Programa Bolsa Família. CONCLUSÃO Aproximadamente um em cada dez brasileiros apresenta DM. Um pouco mais da metade desta população tem conhecimento do seu diagnóstico, condição aferida por dosagem de HbA1c e diagnóstico clínico. Entre os que sabem, a grande maioria está sob tratamento medicamentoso. Porém, menos da metade destes tem seus níveis de HbA1c controlados. Cenários piores foram encontrados em subgrupos com alta vulnerabilidade social.

Perfiles de hipoglicemiantes e insulinas en pacientes con diabetes mellitus tipo 2 y su efecto en control metabólico, hipoglicemia y otros efectos adversos / Profile of glucose lowering drug use in outpatients with type 2 diabetes mellitus

BACKGROUND: The use of glucose lowering agents with favorable weight profile is a growing practice in Diabetology. AIM: To characterize medication combinations in patients with type 2 Diabetes (T2D) and their effect on metabolic control. MATERIAL AND METHODS: Review of medical records of 249 outpatients with T2D with a median age of 66 years, cared for at a medical network. Clinical characteristics, glycated hemoglobin (HbA1c), details of Diabetes treatment (types of drugs or insulin), renal function, lipids and B12 vitamin levels were registered. RESULTS: The median disease duration was 16 years. The most recent HbA1c was 7.4%. No patient was using sulfonylureas, 45 were using Dipeptidyl peptidase 4 inhibitors, 113 were using Sodium-glucose Cotransporter-2 (SGLT2i) Inhibitors, 21 used Glucagon-like Peptide-1 Receptor Agonists (GLP1ra), 158 used basal insulin and 61 on basal plus bolus insulin. The use of SGLT2i or GLP1ra was associated with a metabolic control similar to those patients not using them, while patients on rapid insulin had a significantly worse metabolic control and a tendency to greater body mass index. The use of basal insulin and rapid insulin was significantly associated with more hypoglycemia events. CONCLUSIONS: The use of SGLT2i and GLP1ra in patients with T2D is associated with better metabolic control than rapid insulin with less risk of hypoglycemia. The use of these therapies should be prioritized in the future.

Dose-ranging effects of SGLT2 inhibitors in patients with type 2 diabetes: a systematic review and meta-analysis

ABSTRACT The lowest dosage of empagliflozin (10 mg) showed similar benefits on glycated hemoglobin (HbA1c) level, body weight, blood pressure, and total and cardiovascular mortality in comparison with the highest available dose (25 mg) in the EMPAREG trial. These findings have not been clearly demonstrated for canagliflozin and dapagliflozin. The objective was to compare the effect of different doses of SGLT2 inhibitors commercially available in Brazil on HbA1c and body weight of patients with type 2 diabetes. MEDLINE, Cochrane and Embase databases were searched from inception until 11th October 2021 for randomized controlled trials of SGLT2 inhibitors in type 2 diabetes patients, lasting at least 12 weeks. HbA1c and body weight variations were described using standard mean difference. We performed direct and indirect meta-analysis, as well as a meta-regression with medication doses as covariates. Eighteen studies were included, comprising 16,095 patients. In the direct meta-analysis, SGLT2 inhibitors reduced HbA1c by 0.62% (95% CI −0.66 to −0.59) and body weight by 0.60 kg (95% CI −0.64 to −0.55). In the indirect meta-analysis, canagliflozin 300 mg ranked the highest regarding reductions in HbA1c and body weight. The remaining medications and dosages were clinically similar, despite some statistically significant differences among them. Canagliflozin 300 mg seems to be more potent in reducing HbA1c and body weight in patients with type 2 diabetes. The remaining SGLT2 inhibitors at different doses lead to similar effects for both outcomes. Whether these glycemic and weight effects are reflected in lower mortality and cardiovascular events is still uncertain and may be a topic for further studies.

Effect of Prosopis ruscifolia on incretin and insulin secretion in alloxan-induced hyperglycemic rats / Efecto de Prosopis ruscifolia sobre la secreción de incretina e insulina de ratas hiperglicémicas por aloxano

Background: Diabetes mellitus treatment is based on oral hypoglycemic agents or insulin. Medicinal plants constitute an option, and the leaves of Prosopis ruscifolia (Pr) were shown to be effective in reducing glycemia in hyperglycemic animals. Objective: In this paper, we report the effect of P. rusciofolia (Pr) on insulin and incretin secretion in alloxan-induced hyperglycemic rats. Methodology: The effective dose was selected, and four groups (n=10) of Wistar rats were used. Two groups with normal glycemia received water or Pr (75 mg/Kg, per os, p.o.), and two groups with hyperglycemia induced by alloxan (intraperitoneal, ip), received water or Pr (75 mg/Kg, p.o.) for 2 weeks. Oral glucose tolerance test, and incretin and insulin levels were measured at the end of the experimental period. Results: The results showed that extract promotes better tolerance to oral glucose overload, in addition to a statistically significant (p<0.001) increase in blood levels of incretin and insulin, compared to the hyperglycemic rats. Conclusion: It is concluded that the ethanolic extract of P. ruscifolialeaves has a hypoglycemic effect in hyperglycemic animals by a mechanism that involves the incretin-insulin system

Antecedentes: la diabetes mellitus es una enfermedad metabólica cuyo tratamiento se basa en el uso de agentes hipoglicemiantes orales o insulina. Una opción al tratamiento son las plantas medicinales y en ese sentido, estudios previos en animales con hojas de Prosopis ruscifolia (Pr) han demostrado efecto hipoglicemiante. Objetivo: en este trabajo se reporta el efecto de P. rusciofolia (Pr) en la secreción de insulina e incretina, en ratas hiperglicémicas por aloxano. Metodología: se emplearon cuatro grupos de ratas Wistar (n=10). Dos grupos con glicemia normal que fueron tratadas con agua Pr (75 mg/Kg, per os, p.o.) y dos grupos con hiperglicemia inducida por la inyección intraperitoneal de aloxano recibieron agua Pr (75 mg/Kg, per os, p.o.) durante dos semanas. Se midieron la tolerancia oral a la glucosa, y los niveles de incretina e insulina al final del periodo de experimentación. Resultados: se encontró que el extracto promueve una mayor tolerancia a la sobrecarga de glucosa, y además un incremento significativo (p<0.001) de los niveles de incretina e insulina en sangre, comparados al grupo de ratas hiperglicémicas. Conclusión: se concluye que e l estracto etanólico de las hojas de P. ruscifolia tienen efecto hipoglicemiante en animales hiperglicémicos por un mecanismo que incluye al sistema incretina-insulina

New practice in semaglutide on type-2 diabetes and obesity: clinical evidence and expectation / 医学前沿

Obesity is an important risk factor of type 2 diabetes (T2D), which has become an important factor threatening human health. However, no perfect drug choice for obesity exists. Semaglutide is a kind of human glucagon-like peptide-1 (GLP-1) analog that promotes insulin secretion while inhibiting glucagon secretion through a glucose concentration-dependent mechanism. GLP-1 can also delay stomach emptying and suppress appetite to help lose weight. This review summarizes clinical evidence of the semaglutide effect on T2D and obesity and establishes expectations on future clinical trials for obesity treatment.

Factors associated with glycemic variability in children with type 1 diabetes mellitus based on flash glucose monitoring system / 中南大学学报(医学版)

OBJECTIVES@#Patients with classical type 1 diabetes mellitus (T1DM) require lifelong dependence on exogenous insulin therapy due to pancreatic beta-cell destruction and absolute insulin deficiency. T1DM accounts for about 90% of children with diabetes in China, with a rapid increase in incidence and a younger-age trend. Epidemiological studies have shown that the overall glycated haemoglobin (HbA1c) and compliance rate are low in Chinese children with T1DM. Optimal glucose control is the key for diabetes treatment, and maintaining blood glucose within the target range can prevent or delay chronic vascular complications in patients with T1DM. Therefore, this study aims to investigate the glycemic control of children with T1DM from Hunan and Henan Province with flash glucose monitoring system (FGMS), and to explore factors associated with glycemic variability.@*METHODS@#A total of 215 children with T1DM under 14 years old were enrolled continuously in 16 hospitals from August 2017 to August 2020. All subjects wore a FGMS device to collect glucose data. Correlation of HbA1c, duration of diabetes, or glucose scan rates with glycemic variability was analyzed. Glucose variability was compared according to the duration of diabetes, HbA1c, glucose scan rates and insulin schema.@*RESULTS@#HbA1c and duration of diabetes were positively correlated with mean blood glucose, standard deviation of glucose, mean amplitude of glucose excursions (MAGE), and coefficient of variation (CV) of glucose (all P<0.01). The glucose scan rates during FGMS wearing was significantly positively correlated with time in range (TIR) (P=0.001) and negatively correlated with MAGE and mean duration of hypoglycemia (all P<0.01). Children with duration ≤1 year had lower time below range (TBR) and MAGE when compared with those with duration >1 year (all P<0.05). TIR and TBR in patients with HbA1c ≤7.5% were higher (TIR: 65% vs 45%, TBR: 5% vs 4%, P<0.05), MAGE was lower (7.0 mmol/L vs 9.4 mmol/L, P<0.001) than those in HbA1c >7.5% group. Compared to the multiple daily insulin injections group, TIR was higher (60% vs 52%, P=0.006), MAGE was lower (P=0.006) in the continuous subcutaneous insulin infusion group. HbA1c was lower in the high scan rates (≥14 times/d) group (7.4% vs 8.0%, P=0.046), TIR was significantly higher (58% vs 47%, P<0.001), and MAGE was lower (P<0.001) than those in the low scan rate (<14 times/d) group.@*CONCLUSIONS@#The overall glycemic control of T1DM patients under 14 years old in Hunan and Henan Province is under a high risk of hypoglycemia and great glycemic variability. Shorter duration of diabetes, targeted HbA1c, higher glucose scan rates, and CSII are associated with less glycemic variability.

Efficacy and Safety of Mulberry Twig Alkaloids Tablet for Treatment of Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Multicenter Clinical Study / 中国结合医学杂志

OBJECTIVE@#To assess the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids, SZ-A) for treatment of type 2 diabetes in a randomized, double-blind, placebo-controlled multicenter clinical trial.@*METHODS@#A total of 200 patients were randomized to receive SZ-A (n=100) or placebo (n=100) for 16 weeks. The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs. The primary outcome was the change in glycosylated hemoglobin (HbA1c) level. The secondary outcome included the proportions of cases with HbA1c <7.0% and HbA1c <6.5%, fasting blood glucose (FBG), postprandial blood glucose (PBG), area under curve for the PBG (AUC0-2h), body weight, and body mass index (BMI). Adverse events (AEs), severe adverse events (SAEs), treatment-related adverse events (TAEs), gastrointestinal disorders (GDs), blood pressure, routine blood tests, and liver and kidney function were monitored.@*RESULTS@#Compared with baseline, the change of HbA1c at week 16 was -0.80% (95% CI: -0.98% to -0.62%) and -0.09% (95% CI: -0.27% to 0.09%) in SZ-A group and placebo group, respectively. The proportion of patients with HbA1c <7% and <6.5% was higher in the SZ-A group than in the placebo group (46.8% vs. 21.6% and 29.9% vs. 10.8%). The observed values and changes in FBG, 1 h-PBG, 2 h-PBG, and AUC0-2h differed significantly between groups (P<0.001), but differences were not significant in body weight and BMI (P>0.05). The incidence rates of AEs, TAEs, and GDs differed significantly between groups (P=0.010, P=0.005, and P=0.006, respectively), whereas the incidence rates of SAEs showed no significant differences between groups (P=1.000).@*CONCLUSION@#SZ-A are effective and safe for treatment of type 2 diabetes. The protocol was registered in http://www.chictr.org.cn/showproj.aspx?proj=60117 (ChiCTR2000038550).

Suppression of diabetes-induced renal inflammatory cell infiltration by metformin associated with the amelioration of renal injury biomarkers / Supresión de la infiltración de células inflamatorias renales de diabetes-inducida, por metformina asociada con la mejora de los biomarcadores de lesión renal

SUMMARY: Diabetes and hypertension account for the majority of chronic kidney injury cases that can lead to renal failure. The link between the leukocytes common antigen (CD45) and diabetic kidney disease (DKD) with and without metformin incorporation in an animal model has not been investigated before. Therefore, we sought to assess the extent of leukocytes infiltration into kidney tissues 10 weeks following the induction of diabetes in rats treated with metformin. In addition, we monitored blood and urine parameters associated with diabetes. The model group of rats received streptozotocin (STZ; 50 mg/kg) injection after being fed for 14 days on a high-fat diet (HFD) and continuously fed a HFD until they were culled, at week 12. The protective group was treated in the same way except that these animals were put from day 1 on metformin (200 mg/kg) until being culled, on week 12. Kidneys were immunostained with CD45 as a marker of leukocytes infiltration and examined by light microscopy. Urine samples were tested for urine albumin and collected blood was analyzed for sugar, urea, creatinine, and oxidative stress and antioxidants biomarkers. Kidney injury secondary to diabetes was developed as demonstrated by (i) increased blood glucose, urea, and malondialdehyde (MDA) as a marker of lipid peroxidation; and (ii) kidney tissue damage and marked increase in kidney tissues expressing CD45 positive cells. The above markers were inhibited (p0.0006) by metformin. Also, a significant correlation was observed between CD45 score and glycemia, urea, MDA, and the antioxidant superoxide dismutase (SOD). Thus, our data demonstrate an association between the infiltration of CD45+ inflammatory cells into kidney tissues and biomarkers of kidney damage in a rat model of DKD, which was effectively protected by metformin.

RESUMEN: La diabetes y la hipertensión representan la mayoría de los casos de lesión renal crónica que pueden provocar insuficiencia renal. El vínculo entre el antígeno común de los leucocitos (CD45) y la enfermedad renal diabética (DKD) con y sin incorporación de metformina en un modelo animal no se había anteriormente investigado. El objetivo fue evaluar el grado de infiltración de leucocitos en los tejidos renales 10 semanas después de la inducción de diabetes en ratas tratadas con metformina. Además, monitoreamos los parámetros de sangre y orina asociados con la diabetes. El grupo modelo de ratas recibió una inyección de estreptozotocina (STZ; 50 mg/kg) después de ser alimentadas durante 14 días con una dieta alta en grasas (HFD) y continuamente alimentadas con un HFD hasta que fueron sacrificadas, en la semana 12. El grupo protector fue tratado de la misma manera excepto que estos animales fueron recibieron desde el día 1 metformina (200 mg/kg) hasta ser sacrificados, en la semana 12. Los riñones fueron inmunoteñidos con CD45 como marcador de infiltración de leucocitos y examinados por microscopía óptica. Las muestras de orina se analizaron en busca de albúmina y la sangre recolectada se analizó en busca de glucosa, urea, creatinina y biomarcadores de estrés oxidativo y antioxidantes. La lesión renal secundaria a la diabetes se desarrolló como lo demuestra (i) el aumento de la glucosa en sangre, la urea y el malondialdehído (MDA) como marcador de la peroxidación lipídica; y (ii) daño del tejido renal y marcado aumento en los tejidos renales que expresan células positivas para CD45. Los marcadores anteriores fueron inhibidos (p≤0.0006) por metformina. Además, se observó una correlación significativa entre la puntuación de CD45 y la glucemia, la urea, la MDA y la superóxido dismutasa antioxidante (SOD). Por lo tanto, nuestros datos demuestran una asociación entre la infiltración de células inflamatorias CD45+ en los tejidos renales y biomarcadores de daño renal en un modelo de rata con DKD, que fue protegido de manera efectiva por metformina.

Metformin versus glyburide in treatment and control of gestational diabetes mellitus: a systematic review with meta-analysis

ABSTRACT Objective To compare the major outcomes of use of metformin and glyburide in treatment of gestational diabetes mellitus. Methods Studies published in English, in the last 10 years, in the databases MEDLINE®, SciELO, LILACS and Cochrane Library were analyzed, and randomized controlled trials were selected. Health Sciences Descriptors were used to compose the search phrase, and the keywords "Gestational diabetes", "Glyburide", "Metformin" and their variations were searched in the Medical Subject Headings. PRISMA systematization was used to prepare this review, and a meta-analysis was conducted aiming to mathematically show the results of fasting blood glucose, postprandial blood glucose, birth weight and weight gain during pregnancy after using metformin and glyburide. Results The studies evaluated birth weight, neonatal hypoglycemia, mode of delivery, need for intensive care, Apgar score, macrosomia, fasting glucose, postprandial glucose and weight gain during pregnancy. In 60% of studies, there were no statistically significant differences regarding safety and efficacy of administration of metformin and glyburide. Meta-analysis demonstrated the absence of statistical differences between these drugs in fasting blood glucose (p=0.821), postprandial blood glucose (p=0.217) and birth weight (p=0.194). However, significant differences were shown in weight gain during pregnancy (p=0.036). Conclusion The methods are effective, but the adverse effects of glyburide are more common; therefore, the use of metformin should be recommended, if in monotherapy.

Adesão ao tratamento e qualidade de vida em população diabética admitida em serviço público / Adherence to treatment and quality of life in a diabetic population admitted to a public service facility

Objetivo: Avaliar a adesão ao tratamento e a qualidade de vida de pacientes diabéticos e identificar características epidemio- lógicas e da doença relacionadas. Métodos: Estudo transversal realizado com 98 pacientes diabéticos em acompanhamento. Foram aplicados: um questionário sociodemográfico; o Diabe- tes Quality of Life na versão brasileira, para avaliar qualidade de vida, e o teste Morisky-Green-Levine, para checar a adesão ao tratamento. O nível de significância adotado foi de 5%. Resul- tados: A maioria (87,8%) dos pacientes apresentou boa quali- dade de vida. O escore médio de qualidade de vida foi de 2,2. Existência de complicações, uso de insulina e má adesão ao tra- tamento foram fatores associados à pior qualidade de vida. A boa adesão ao tratamento (58,2%) foi associada à boa qualidade de vida (p<0,001). Conclusão: A boa adesão ao tratamento está relacionada à boa qualidade de vida. Deve-se enfatizar a impor- tância da adesão ao tratamento para prevenção de possíveis com- plicações e manutenção da qualidade de vida.

Objective: To evaluate adherence to treatment and quality of life of diabetic patients and to identify related epidemiological and disease characteristics. Methods: Cross-sectional study conducted with 98 diabetic patients undergoing treatment. A socio-demographic questionnaire, the Diabetes Quality of Life in the Brazilian version (to measure quality of life) and the Mo- risky-Green-Levine test (to check adherence to treatment) were applied. The level of significance was set at 5%. Results: Most patients (87.8%) showed good quality of life. The mean score of quality of life was 2.2. The existence of complications, insulin use, and poor treatment adherence were factors associated with worse quality of life. Good adherence to treatment, (58.2%) was associated with good quality of life (p<0.001). Conclusion: Satis- factory treatment adherence is associated with good quality of life. The importance of adherence to treatment to prevent possible complications and maintain quality of life shall be emphasized.

Hypoglycemia frequency and treatment satisfaction in patients receiving insulin analogues for treatment of type 1 diabetes mellitus

ABSTRACT Objective: The aim of this study was to evaluate the frequency of hypoglycemia and the treatment satisfaction in patients with type 1 diabetes (T1D) using insulin analogues. Subjects and methods: This observational retrospective study included 516 adult patients with T1D from 38 cities in Southern Brazil. Demographics and clinical data were collected using a self-report questionnaire. Hypoglycemia was defined as an event based on either symptoms or self-monitored blood glucose < 70 mg/dL. Treatment satisfaction was evaluated using the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) and with a specific question with scores ranging from 0-10. Common mental disorders were assessed using the General Health Questionnaire (GHQ-12). Results: Overall, the mean age was 38 ± 14 years and 52% of the participants were women. The median diabetes duration was 18 years. The scores for insulin analogue treatment satisfaction were higher than those for previous treatments. DTSQ scores had a median value of 32 (interquartile range 29-35) and remained unchanged over time. The percentage of patients with hypoglycemia (including severe and nocturnal) was comparable across groups divided according to duration of use of insulin analogues. Most patients (n=395, 77%) screened positive for common mental disorders. Conclusions: Patient satisfaction with insulin analogue treatment was high and remained unchanged with time. Episodes of hypoglycemia also remained unchanged over time among patients using insulin analogues.

Efficacy of a glucose meter connected to a mobile app on glycemic control and adherence to self-care tasks in patients with T1DM and LADA: a parallel-group, open-label, clinical treatment trial

ABSTRACT Objective: The main aim of the study was to evaluate the patients' glycemic control and adherence to self-care tasks. Materials and methods: Patients with type 1 diabetes mellitus (T1DM) or latent autoimmune diabetes of the adult (LADA) using a multiple daily injection (MDI) regimen with carbohydrate counting (n = 25, Subgroup B) or fixed insulin dose (n = 25, Subgroup C) were allocated to use the application (app) for 12 weeks. Both subgroups were compared with each other and against a control group (n = 25, Group A) comprising patients with T1DM or LADA treated with continuous subcutaneous insulin infusion (CSII) in a parallel-group, open-label, clinical treatment trial. All patients had glycated hemoglobin (A1C) levels measured and were asked to fill out the Diabetes Self-Management Profile (DSMP) questionnaire at study start and end. The patients were instructed to measure capillary glucose six times daily in study weeks 4, 8, and 12. Results: Mean A1C levels decreased 0.725% in Subgroup C in intragroup analysis (p = 0.0063), and had a mean variation of 0.834% compared with Group A (p = 0.003). Mean DSMP scores increased 5.77 points in Subgroup B in intragroup analysis (p = 0.0004) and increased by a mean of 6.815 points in relation to Group A (p = 0.002). Conclusion: OneTouch Reveal improved both A1C levels and DSMP scores in patients with T1DM or LADA compared with standard treatment (CSII).

Effectiveness of triple therapy with dapagliflozin add-on to dual therapy over 52 weeks in patients with uncontrolled type 2 diabetes mellitus in a centre of high complexity, Cali-Colombia

ABSTRACT Objectives: To evaluate the effectiveness of adding dapagliflozin as an intensification strategy for the treatment of patients with uncontrolled type 2 diabetes mellitus (T2DM). Materials and methods: A historical cohort study was conducted in 123 adult patients over 18 years old who were diagnosed with uncontrolled T2DM, who received dapagliflozin add-on to their dual base treatment: metformin plus glibenclamide (n = 32), metformin plus saxagliptin (n = 29), metformin plus exenatide (n = 28), or metformin plus insulin (n = 34). The endpoints were evaluated using analysis of variance. Results: All the patients completed a 52-week follow-up. Overall, 52.85% of patients were female, the Hispanic population represented the largest proportion of patients in all groups (60.98%), and the mean ± SD patient age and body weight were 55.05 ± 7.58 years and 83.55 ± 9.65 kg, respectively. The mean ± SD duration of T2DM, glycated hemoglobin (HbA1c), and fasting plasma glucose (FPG) were 5.93 ± 2.98 years, 8.1 ± 0.53%, and 166.03 ± 26.80 mg/dL, respectively. The grand mean changes of HbA1c, FPG, body weight and blood pressure showed a decreasing trend during the study period and it was statistically significant in all groups (p-value = <0.001). The proportion of patients achieving HbA1c target (<7%) was highest in the group that used a dapagliflozin add-on to metformin plus saxagliptin. Conclusion: The addition of dapagliflozin as an alternative for intensification of dual therapy consistently improved, not only FPG and HbA1c, but also body weight and blood pressure, with statistically significant results.

Nuevos hipoglucemiantes en el cuidado de las personas con diabetes tipo 2: por fin hay un avance / New hypoglycemic agents in the care of people with diabetes: finally, there is a breakthrough

En este artículo, la autora jerarquiza la relevancia de la eficacia documentada de los agonistas del péptido similar alglucagón-1 y los inhibidores del cotransportador sodio-glucosa tipo 2, que ha conducido a recientes modificaciones en el paradigma del cuidado en los pacientes con diabetes tipo 2. (AU)

In this article, the author highlights the relevance of the documented efficacy of glucagon-like peptide-1 agonists and type 2 sodium-glucose cotransporter inhibitors, which has led to recent changes in the paradigm of care in patients with type 2diabetes. (AU)

Tendência do uso e fontes de obtenção de antidiabéticos orais para tratamento de diabetes no Brasil de 2012 a 2018: análise do inquérito Vigitel / Tendency of use and sources for obtaining oral antidiabetic drugs for treatment of diabetes in Brazil from 2012 to 2018: analysis of the Vigitel survey

RESUMO: Objetivo: Estimar as prevalências de uso de medicamento oral para tratamento de diabetes, bem como a distribuição das fontes de obtenção segundo variáveis sociodemográficas, nas capitais dos estados brasileiros e no Distrito Federal e sua evolução no período de 2012 a 2018. Métodos: Estudo transversal de base populacional com indivíduos de 20 anos ou mais que referiram diagnóstico médico de diabetes, entrevistados pelo Sistema de Vigilância de Fatores de Risco e Proteção para Doenças Crônicas por Inquérito Telefônico (Vigitel) de 2012 a 2018. Estimaram-se a prevalência de uso e a distribuição das fontes de obtenção segundo variáveis sociodemográficas (IC95%). Verificaram-se as diferenças entre as proporções pelo teste χ2 de Pearson (Rao-Scott), com nível de significância de 5%. Resultados: Houve aumento na prevalência de uso de medicamento oral para tratamento de diabetes de 77,4 para 85,2%, entre 2012 e 2018, e diminuição da obtenção nas farmácias de unidade de saúde do Sistema Único de Saúde (SUS) com aumento da obtenção nas farmácias populares. Conclusões: O SUS manteve-se como a principal fonte de obtenção de antidiabéticos orais no Brasil, financiando mais de 70% dos medicamentos orais para tratamento de diabetes no país, considerando as farmácias de unidades de saúde e as farmácias populares, mostrando, assim, a importância das políticas farmacêuticas públicas na garantia do acesso a medicamentos pela população brasileira e na diminuição das iniquidades no país. Contudo a migração da obtenção pelos usuários nas unidades de saúde do SUS para as farmácias populares sugere enfraquecimento da responsabilidade da atenção primária à saúde na oferta de medicamentos antidiabéticos orais, fragilizando o vínculo e o cuidado longitudinal.

ABSTRACT: Objective: To estimate the prevalence of use of oral medications for the treatment of diabetes, as well as the distribution of sources for obtaining according to sociodemographic variables, in the Brazilian states' capitals and in the Federal District, and their evolution from 2012 to 2018. Methods: Cross-sectional and population-based study with individuals aged ≥ 20 years who reported a medical diagnosis of diabetes, interviewed through Vigitel from 2012 to 2018. We estimated the prevalence of use and the distribution of sources for obtaining according to sociodemographic variables (95%CI). We checked differences among proportions using the Pearson's χ2 test (Rao-Scott), with a significance level of 5%. Results: There was an increase in the prevalence of use of oral medications for the treatment of diabetes from 77.4 to 85.2% between 2012 and 2018, and a decrease in obtaining in the Health Unit Pharmacies of the Unified Health System (SUS), while there was an increase in obtaining in Popular Pharmacies. Conclusions: In Brazil, SUS remained the main source for obtaining oral antidiabetic drugs, financing more than 70% of them in the country, considering the Health Unit Pharmacies and Popular Pharmacies, thereby showing the importance of public Pharmaceutical Policies in guaranteeing the access to medications by the Brazilian population, as well as in reducing inequities in the country. Nevertheless, the migration of obtaining by users from SUS Health Units to Popular Pharmacies suggests the weakening the responsibility of Primary Health Care in the provision oral antidiabetic drugs, thereby undermining the bond and the longitudinal care.