Real-world safety and effectiveness of dapagliflozin in people living with type 1 diabetes in Spain: The Dapa-ON multicenter retrospective study.

OBJECTIVE: To assess real-world safety and effectiveness of dapagliflozin in people living with type 1 diabetes mellitus (T1DM). METHODS: We conducted a multicenter retrospective study in Spain including data from 250 people living with T1DM receiving dapagliflozin as add-on therapy to insulin (80.8 % on-label use). The number of diabetic ketoacidosis (DKA) events was calculated over a 12-month follow-up (primary outcome). Changes in body weight, HbA1c, total daily insulin dose, and continuous glucose monitoring (CGM) metrics from baseline (at dapagliflozin prescription) to 12 months were also evaluated. RESULTS: A total of five DKA events (2.4 % [95 % CI 0.3;4.5] were reported in patients with a 12-month follow-up, n = 207): two events related to insulin pump malfunction, two events related to concomitant illnesses, and one event related to insulin dose omission. DKA events were more frequent among insulin pump users than among participants on multiple daily injections (7.7 % versus 1.2 %). Four of the reported DKA events occurred within the first six months after initiation of dapagliflozin. No deaths or persistent sequelae due to DKA were reported. No severe hypoglycemia episodes were reported. Significant reductions in mean body weight (-3.3 kg), HbA1c (-0.6 %), and total daily insulin dose (-8.6 %), P < 0.001, were observed 12 months after dapagliflozin prescription. Significant improvements in TIR (+9.3 %), TAR (-7.2 %), TBR (-2.5 %), and coefficient of variation (-5.1 %), P < 0.001, were also observed in the subgroup of patients with available CGM data. Finally, an improvement in urinary albumin-to-creatinine ratio (UACR) was found among participants with UACR ≥ 30 mg/g at baseline (median decrease of 99 mg/g in UACR, P = 0.001). CONCLUSION: The use of dapagliflozin in people living with T1DM has an appropriate safety profile after careful selection of participants and implementation of strategies to reduce the risk of DKA (i.e., prescribed according to the recommendations of the European Medicines Agency), and also leads to clinical improvements in this population.

Effectiveness and Tolerability of the Intensification of Canagliflozin Dose from 100 mg to 300 mg Daily in Patients with Type 2 Diabetes in Real Life: The INTENSIFY Study.

Aim: This study aimed to evaluate the effectiveness and tolerability of intensifying the dose of canagliflozin from 100 mg/day (CANA100) to 300 mg/day (CANA300) in patients with type 2 diabetes (T2DM) and suboptimal metabolic control in a real-world setting. Methods: A multicenter observational study was conducted on adult patients with T2DM who initiated treatment with CANA100 and subsequently required intensification to CANA300. The primary outcome measures were changes in HbA1c and weight at 6 months after the switch and at the end of the follow-up period. Results: A total of 317 patients met the inclusion criteria (59.6% male, mean age 62.2 years, baseline HbA1c 7.55%, weight 88.6 kg, median duration of treatment with CANA100 9.9 months). Switching to CANA300 resulted in a significant reduction in HbA1c (6 months: -0.33%; last visit: -0.47%, both p < 0.0001) and weight (6 months: -1.8 kg; last visit: -2.9 kg, both p < 0.0001) over a median follow-up period of 20.8 months. The proportion of patients that achieved HbA1c < 7% increased from 26.7% with CANA100 to 51.6% with CANA300 (p < 0.0001). Among individuals with poor baseline glycemic control (HbA1c > 8%, mean 9.0%), HbA1c was significantly reduced by -1.24% (p < 0.0001). Furthermore, significant improvements were observed in fasting plasma glucose (FPG), blood pressure (BP), liver enzymes, and albuminuria. No unexpected adverse events were reported. Conclusions: Intensifying the treatment to CANA300 in a real-world setting resulted in further significant and clinically relevant reductions in FPG, HbA1c, weight, and BP in patients with T2DM. The switch was particularly effective in patients with higher baseline HbA1c levels.

Predictive Factors of Renal Function Decline in Patients with Type 2 Diabetes Treated with Canagliflozin in the Real-Wecan Study.

The Real-WECAN study evaluated the real-life effectiveness and safety of canagliflozin 100 mg daily (initiated in SGLT-2 inhibitors naïve patients) and canagliflozin 300 mg daily (switching from canagliflozin 100 mg or other SGLT-2 inhibitors) in individuals with type 2 diabetes. The objectives of this sub-analysis were to estimate the eGFR slope over the follow-up period and to identify predictive factors of eGFR decline in a multiple linear regression analysis. A total of 583 patients (279 on canagliflozin 100 mg and 304 on canagliflozin 300 mg) were included, with median follow-up at 13 months. The patients had a mean age of 60.4 years, HbA1c of 7.76%, BMI of 34.7 kg/m2, eGFR below 60 mL/min/1.73 m2 8.6%, and urine albumin-to-creatinine ratio (UACR) above 30 mg/g 22.8%. eGFR decreased by −1.9 mL/min/1.73 m2 (p < 0.0001) by the end of the study. The mean eGFR slope during the maintenance phase was −0.16 mL/min/1.73 m2 per year. There were no significant differences between both doses of canagliflozin in the eGFR reduction or in the eGFR slope. The best predictive multivariate model of eGFR decline after canagliflozin therapy included age, hypertension, combined hyperlipidemia, heart failure, eGFR and severely increased albuminuria. All these variables except hypertension were independently associated with the outcome. In conclusion, in this real-world study, individuals with older age, combined hyperlipidemia, heart failure, higher eGFR and UACR > 300 mg/g showed a greater decline in their eGFR after canagliflozin treatment.

Real-World Clinical Outcomes Associated with Canagliflozin in Patients with Type 2 Diabetes Mellitus in Spain: The Real-Wecan Study.

The aims of this multicentric retrospective study were to assess in a real-world setting the effectiveness and safety of canagliflozin 100 mg/d (CANA100) as an add-on to the background antihyperglycemic therapy, and to evaluate the intensification of prior sodium-glucose co-transporter type 2 inhibitor (SGLT-2i) therapy by switching to canagliflozin 300 mg/d (CANA300) in patients with T2DM. One cohort of SGLT2i-naïve patients with T2DM who were initiated on CANA100 and a second cohort of patients with prior background SGLT-2i therapy who switched to CANA300 were included in the study. The primary outcome of the study was the mean change in HbA1c over the follow-up time. In total, 583 patients were included-279 in the cohort of CANA100 (HbA1c 8.05%, weight 94.9 kg) and 304 in the cohort of CANA300 (HbA1c 7.51%, weight 92.0 kg). Median follow-up periods in both cohorts were 9.1 and 15.4 months respectively. CANA100 was associated to significant reductions in HbA1c (-0.90%) and weight (-4.1 kg) at the end of the follow-up. In those patients with baseline HbA1c > 8% (mean 9.25%), CANA100 lowered HbA1c levels by 1.51%. In the second cohort, patients switching to CANA300 experienced a significant decrease in HbA1c (-0.35%) and weight (-2.1 kg). In those patients with baseline HbA1c > 8% (mean 8.94%), CANA300 lowered HbA1c levels by 1.12%. There were significant improvements in blood pressure in both cohorts. No unexpected adverse events were reported. In summary, CANA100 (as an add-on therapy) and CANA300 (switching from prior SGLT-2i therapy) significantly improved several cardiometabolic parameters in patients with T2DM.

Real-world clinical outcomes and predictors of glycaemic and weight response to exenatide once weekly in patients with type 2 diabetes: The CIBELES project.

AIMS: To evaluate in a real-world setting the effectiveness of exenatide once-weekly (ExQW) in patients with T2D and to determine predictors of glycaemic and weight response to this drug at 6 months. METHODS: Observational, retrospective, multicenter study in adult patients with T2D and BMI ≥30 kg/m2 from 4 tertiary Spanish hospitals who started ExQW therapy at least 6 months before the inclusion and had not achieved adequate glycaemic control on oral therapies or other GLP-1 receptor agonists. Glycaemic response was defined as an A1C reduction ≥1.0% and weight response as a weight loss ≥3% 6 months after ExQW. The best predictive models of glycaemic and weight response were estimated by binary logistic regression. RESULTS: One hundred and forty eight patients were included, mean age 58.0 years, A1C 7.7%, weight 105.9 kg and BMI 38.4 kg/m2 . A1C (-1.1%), weight (-3.9 kg), systolic blood pressure (-4.0 mm Hg), diastolic blood pressure (-2.9 mm Hg), LDL-cholesterol (-14.2 mg/dL) and triglycerides (-31.0 mg/dL) significantly decreased 6 months after ExQW. 41.5% of patients had an A1C reduction ≥1.0% and 53.1% lost ≥3% of baseline weight. Glycaemic and weight reductions were sustained in patients completing 1 and 2 years of follow-up. The best predictive model of glycaemic response only included higher A1C levels (OR 3.9), whereas higher BMI (OR 1.1) and prior DPP-4i therapy (OR 3.1) were associated to weight response in the multivariate analysis. CONCLUSIONS: In a real-world setting, ExQW significantly decreased A1C, weight, blood pressure and lipids at 6 months. Our study identified higher baseline A1C as the sole independent predictor of glycaemic response to ExQW and higher BMI and previous DDP4i treatment as predictive factors of meaningful weight response.

The effect of concomitant DPPIVi use on glycaemic control and hypoglycaemia with insulin glargine 300 U/mL (Gla-300) versus insulin glargine 100 U/mL (Gla-100) in people with type 2 diabetes: A patient-level meta-analysis of EDITION 2 and 3.

AIMS: To evaluate the effect of concomitant dipeptidyl peptidase IV inhibitor (DPPIVi) use on efficacy and safety of insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100) in people with type 2 diabetes on oral antihyperglycaemic drugs. METHODS: A post hoc patient-level meta-analysis was performed using data from EDITION 2 (basal insulin [N = 811]) and EDITION 3 (insulin-naïve [N = 878]), multicentre, randomised, open-label, parallel-group, phase 3a trials of similar design. Endpoints analysed included HbA1c, hypoglycaemia and adverse events, investigated in subgroups of participants with and without concomitant DPPIVi use. RESULTS: Of 1689 participants randomised, 107 (13%, Gla-300) and 133 (16%, Gla-100) received DPPIVi therapy. The least squares mean change in HbA1c (baseline to month 6) was comparable between treatment groups, irrespective of DPPIVi use (no evidence of heterogeneity of treatment effect across subgroups, p = 0.753), although group sizes were unbalanced. The cumulative mean number of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemic events, and the risk and annualised rate of such events, were consistently lower for Gla-300 than Gla-100 during the night (between 00:00 and 05:59 h) or at any time of day (24 h period), irrespective of DPPIVi use. Severe hypoglycaemia occurred in 8/838 and 10/844 participants in the Gla-300 and Gla-100 groups, respectively, and was not affected by DPPIVi use. The adverse event profile was similar between treatment groups and DPPIVi subgroups. CONCLUSIONS: Glycaemic control with Gla-300 was comparable to Gla-100, with less hypoglycaemia during the night and at any time of day (24 h), irrespective of concomitant DPPIVi use. TRIAL REGISTRATION: ClinicalTrials.gov NCT01499095; NCT01676220.

Switching from Premixed Insulin To Basal Insulin Analogue For Type 2 Diabetes and Role of Dipeptidyl Peptidase-4 Inhibitors.

INTRODUCTION: This study aimed to confirm the usefulness of basal insulin analogue plus oral antidiabetic drugs (OADs) for type 2 diabetes (T2D) patients inadequately controlled with premixed insulin with/without OADs and assess the role of dipeptidyl peptidase-4 (DPP-4) inhibitors within this regimen in clinical practice. METHODS: Spanish retrospective observational study that included 186 T2D patients with glycosylated hemoglobin (HbA1c) >7% (53 mmol/mol) despite premixed insulin with/without OADs who had been switched to basal insulin analogue plus OADs. Study data describing the situation before the treatment switch and 6 months later was retrospectively retrieved from patients' medical charts. RESULTS: Switching to a basal insulin plus OADs decreased HbA1c (-1.0%, p<0.001), fasting (-38.1 mg/dl, p<0.001) and postprandial glycemia (-36.1 mg/dl, p<0.001), with reduced body weight (-1.1 kg, p<0.001) and hypoglycemic episodes (-17.5%, p<0.001). 68 (36.6%) patients received a basal insulin plus DPP-4 inhibitor±metformin and 74 (39.8%) plus metformin only. The DPP-4 inhibitor±metformin group showed a greater HbA1c reduction than the metformin group (1.3±1.4% vs. 0.9±1.0%, p=0.022), with no significant differences between groups in hypoglycemic episodes. CONCLUSIONS: Basal insulin analogue plus OADs may be a useful treatment for type 2 diabetes patients inadequately controlled with premixed insulin. Administering DPP-4 inhibitors within this regimen may contribute to improve patients' glycemia, with a favorable weight-change profile and without increasing hypoglycemia risk.

Practical Approach to Initiating SGLT2 Inhibitors in Type 2 Diabetes.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are an attractive novel therapeutic option for the treatment of type 2 diabetes. They block the reabsorption of filtered glucose in kidneys, mainly in proximal renal tubules, resulting in increased urinary glucose excretion and correction of the diabetes-related hyperglycemia. Beyond improving glucose control, SGLT2 inhibitors offer potential benefits by reducing body weight and blood pressure. On the basis of the efficacy demonstrated in clinical trials, SGLT2 inhibitors are recommended as second- or third-line agents for the management of patients with type 2 diabetes. Beneficial effects on kidney disease progression, cardiovascular and all-cause mortality, and hospitalization for heart failure have also been demonstrated with one SGLT2 inhibitor (empagliflozin). Potential adverse events resulting from their mechanism of action or related to concomitant therapies are reviewed. A treatment algorithm for the adjustment of concomitant therapies after initiating SGLT2 inhibitors is also proposed.

Clinical and metabolic profile of patients with latent autoimmune diabetes in adults in specialized care in Madrid. / Perfil clínico y metabólico de pacientes con diabetes tipo LADA atendidos en atención especializada en la comunidad de Madrid.

OBJECTIVE: To report the clinical characteristics of patients with latent autoimmune diabetes in adults (LADA), and to ascertain their metabolic control and associated chronic complications. METHODS: Patients with DM attending specialized medical care in Madrid who met the following criteria: age at diagnosis of DM >30years, initial insulin independence for at least 6months and positive GAD antibodies were enrolled. Clinical profiles, data on LADA diagnosis, associated autoimmunity, C-peptide levels, therapeutic regimen, metabolic control, and presence of chronic complications were analyzed. RESULTS: Number of patients; 193; 56% females. Family history of DM: 62%. Age at DM diagnosis: 49years. Delay in confirmation of LADA: 3.5years. Insulin-independence time: 12months. Baseline serum C-peptide levels: 0.66ng/ml. Basal-bolus regimen: 76.7%. Total daily dose: 35.1U/day, corresponding to 0.51U/Kg. With no associated oral antidiabetic drugs: 33.5%. Other autoimmune diseases: 57%. Fasting plasma glucose: 160.5mg/dL. HbA1c: 7.7%. BMI: 25.4kg/m2 (overweight, 31.5%; obesity, 8%). Blood pressure: 128/75. HDL cholesterol: 65mg/dL. LDL cholesterol: 96mg/dL. Triglycerides: 89mg/dL. Known chronic complications: 28%. CONCLUSIONS: Recognition of LADA may be delayed by several years. There is a heterogeneous pancreatic insulin reserve which is negative related to glycemic parameters. Most patients are poorly controlled despite intensive insulin therapy. They often have overweight, but have adequate control of BP and lipid profile and a low incidence of macrovascular complications.

Perfil clínico y metabólico de pacientes con diabetes tipo LADA atendidos en atención especializada en la comunidad de Madrid / Clinical and metabolic profile of patients with latent autoimmune diabetes in adults in specialized care in Madrid

Objetivo: Definir las características clínicas de los pacientes con diabetes autoinmune latente del adulto (LADA), conocer su control metabólico y las complicaciones crónicas asociadas que presentan. Métodos: Seleccionamos pacientes con DM seguidos en las consultas de endocrinología de hospitales públicos de la Comunidad de Madrid que reunían los siguientes criterios: edad al diagnóstico de DM >30años, independencia inicial de insulina durante al menos 6meses y positividad de anticuerpos antiGAD. Analizamos datos clínicos relativos al diagnóstico de LADA, autoinmunidad asociada, niveles de péptidoC, pauta terapéutica, control metabólico y presencia de complicaciones crónicas. Resultados: Número de pacientes: 193. Mujeres: 56%. Antecedentes familiares de DM: 62%. Edad al diagnóstico de DM: 49años. Retraso en confirmación LADA: 3,5años. Tiempo de insulino-independencia: 12meses. PéptidoC basal suero: 0,66ng/ml (0,22nmol/l). Pauta de insulina basal-bolus: 76,7%. Dosis total diaria: 35,1U/día, correspondiente a 0,51U/kg. Sin fármacos orales asociados: 33,5%. Presencia de otras patologías autoinmunes: 57%. Glucemia en ayunas: 160,5mg/dl (8,91mmol/l). HbA1c: 7,7%. IMC: 25,4kg/m2 (sobrepeso: 31,5%; obesidad: 8%). Presión arterial: 128/75. Colesterol HDL: 65mg/dl (16,9mmol/l). Colesterol LDL: 96mg/dl (24,96mmol/l). Triglicéridos: 89mg/dl (1,01mmol/l). Complicaciones crónicas: 28%; microangiopatía: 23,1%; macroangiopatía: 4,9%. Conclusiones: El reconocimiento de LADA puede retrasarse varios años. La reserva pancreática de insulina de los pacientes es heterogénea y el grado medio de control glucémico deficiente a pesar de utilizar mayoritariamente insulinoterapia intensiva. Con frecuencia presentan sobrepeso, aunque tienen un control adecuado de la presión arterial y perfil lipídico y baja incidencia de complicaciones macroangiopáticas (AU)

Objective: To report the clinical characteristics of patients with latent autoimmune diabetes in adults (LADA), and to ascertain their metabolic control and associated chronic complications. Methods: Patients with DM attending specialized medical care in Madrid who met the following criteria: age at diagnosis of DM >30years, initial insulin independence for at least 6months and positive GAD antibodies were enrolled. Clinical profiles, data on LADA diagnosis, associated autoimmunity, C-peptide levels, therapeutic regimen, metabolic control, and presence of chronic complications were analyzed. Results: Number of patients; 193; 56% females. Family history of DM: 62%. Age at DM diagnosis: 49years. Delay in confirmation of LADA: 3.5years. Insulin-independence time: 12months. Baseline serum C-peptide levels: 0.66ng/ml. Basal-bolus regimen: 76.7%. Total daily dose: 35.1U/day, corresponding to 0.51U/Kg. With no associated oral antidiabetic drugs: 33.5%. Other autoimmune diseases: 57%. Fasting plasma glucose: 160.5mg/dL. HbA1c: 7.7%. BMI: 25.4kg/m2 (overweight, 31.5%; obesity, 8%). Blood pressure: 128/75. HDL cholesterol: 65mg/dL. LDL cholesterol: 96mg/dL. Triglycerides: 89mg/dL. Known chronic complications: 28%. Conclusions: Recognition of LADA may be delayed by several years. There is a heterogeneous pancreatic insulin reserve which is negative related to glycemic parameters. Most patients are poorly controlled despite intensive insulin therapy. They often have overweight, but have adequate control of BP and lipid profile and a low incidence of macrovascular complications (AU)

Consumo de sal yodada en pacientes de consultas de endocrinología de tres áreas sanitarias de la Comunidad de Madrid / Iodized salt intake in patients attending endocrinology outpatient clinics in three health areas of the Autonomous Community of Madrid

Introducción: Estudios previos muestran que el consumo de sal yodada en diferentes grupos de población española es inferior al recomendado por la Organización Mundial de la Salud para lograr la erradicación de la deficiencia de yodo. El objetivo de este estudio es conocer el consumo de sal yodada en pacientes de consultas de endocrinología de la Comunidad de Madrid. Pacientes y métodos: Se estudió a 2.683 pacientes atendidos en consultas de endocrinología de 3 áreas sanitarias y en una consulta de atención primaria de la Comunidad de Madrid. Se midieron las siguientes variables: consumo de sal yodada, sexo, edad, edad fértil en mujeres, centro sanitario, presencia y tipo de patología tiroidea y contraindicación para consumo de sal yodada. Por razones económicas y organizativas no se evaluaron otras variables, como el estado nutricional de yodo mediante determinación de yoduria o el tipo de sal presente en los hogares de la población encuestada, variables que podrían haber aportado datos más objetivos y confirmatorios del consumo real de sal yodada que los obtenidos exclusivamente de las respuestas dadas por los individuos encuestados. Tras el análisis estadístico bivariado se procedió a la inclusión de las variables independientes en un modelo de regresión logística binaria, siendo la variable dependiente dicotómica el consumo de sal yodada. Resultados: Un 44,6% de los pacientes refirió consumir sal yodada. Su consumo en mujeres en edad fértil y en pacientes con patología tiroidea en la que está contraindicado el uso de sal yodada fue similar al resto de los pacientes. El consumo de sal yodada fue significativamente mayor en mujeres (odds ratio [OR]: 1,47; intervalo de confianza [IC] del 95%: 1,21-1,8) pacientes con patología tiroidea (OR: 1,22, IC del 95%: 1,02-1,44) y pacientes atendidos en consultas de endocrinología (OR: 1,43; IC del 95%: 1,08-1,9). Conclusiones: Menos de la mitad de los pacientes estudiados consume sal yodada, mostrando un nivel de información inadecuado sobre los beneficios para la salud del consumo de sal yodada. Se plantea la necesidad de la realización de campañas institucionales informativas periódicas sobre la importancia de la deficiencia de yodo, que promuevan la generalización del consumo de sal yodada en toda la población española

Introduction: Several previous studies have shown that iodized salt intake in different groups of the Spanish population is lower than that recommended by the World Health Organization to eradicate iodine deficiency. The aim of the present study was to determine iodized salt intake in patients attending endocrinology outpatient clinics in the Autonomous Community of Madrid. Patients and methods: We evaluated 2.683 patients attending endocrinology outpatient clinics in three health areas and one primary care center in the Autonomous Community of Madrid. The following variables were collected: iodized salt intake, sex, age, fertile age in women, health center, presence and type of thyroid disease, and contraindication for iodized salt intake. For economic and management reasons, we did not evaluate other variables such as nutritional iodine status through determination of urinary iodine excretion or the type of salt present in the homes of the population surveyed, which could have provided more objective and confirmatory results on real iodized salt intake than those exclusively obtained from the answers given by the population surveyed. A bivariate statistical analysis was performed and the independent variables were included in a binary logistic regression model with iodized salt intake as the dependent dichotomic variable. Results: A total of 44.6% of the patients reported iodized salt consumption. The intake of iodized salt in women of fertile age and in patients with a diagnosis of thyroid disease contraindicating iodized salt intake was similar to that observed in the remaining patients. The use of iodized salt was significantly higher in women (odds ratio [OR]: 1.47; 95% confidence interval [CI]: 1.21-1.8), patients with thyroid disease (OR: 1.22; 95% CI: 1.02-1.44), and patients attending endocrinology outpatient clinics (OR: 1.43; 95% CI: 1.08-1.9). Conclusions: Less than 50% of the patients consumed iodized salt, revealing that information on the health benefits of iodized salt intake is inadequate. Periodic institutional information campaigns on the importance of iodine deficiency should be implemented to promote widespread iodized salt intake among all sectors of the Spanish population