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Papers by Cristobal Morales

Revista Colombiana de Nefrología

Hemos leído con gran interés el artículo de Braunwald E,1 titulado "Gliflozins in the manage... more Hemos leído con gran interés el artículo de Braunwald E,1 titulado "Gliflozins in the management of cardiovascular disease" publicado recientemente en New England Journal of Medicine, donde el autor hace una excelente revisión de los inhibidores de SGLT2 (iSGLT2) y sus efectos a nivel cardiovascular; sin embargo, consideramos relevante aclarar ciertos puntos al respecto. En Particular, cuando se mencionan los mecanismos de acción de estos fármacos a nivel renal, solo se incluyen los mecanismos hemodinámicos (natriuresis, disminución de la presión intraglomerular, glucosuria, restablecimiento de la retroalimentación túbulo-glomerular, entre otros) que, si bien son muy importantes, cabe agregar que existen mecanismos antiinflamatorios intrarrenales directos dados por la disminución de la glucotoxicidad renal (disminución de especies reactivas de oxígeno, moléculas proinflamatorias, miofibroblastos profibróticos, entre otros). Los efectos antiinflamatorios intrarrenales puede...

BACKGROUND Diabetes is a major health care problem, reaching epidemic numbers worldwide. Reducing... more BACKGROUND Diabetes is a major health care problem, reaching epidemic numbers worldwide. Reducing glycated hemoglobin (HbA1c) levels to recommended targets is associated with a marked decrease in the risk of T2DM-related complications. The implementation of new technologies, particularly telemedicine, may be helpful to facilitate self-care and empowerment of people with T2DM leading to an improved metabolic control of the disease. OBJECTIVE To analyze the effect of a home digital patient empowerment and communication tool (DeMpower App) on metabolic control in people with inadequately-controlled type 2 diabetes mellitus (T2DM). METHODS The DeMpower study was multicenter with a retrospective (observational: 52 weeks of follow-up) and prospective (interventional: 52 weeks of follow-up) design that included people with T2DM, aged ≥18 and ≤80 years, with HbA1c levels ≥7.5% to ≤9.5%, receiving treatment with non-insulin antihyperglycemic agents and able to use a smartphone App. Individua...

Diabetes Therapy

The management of type 2 diabetes (T2D) involves decreasing plasma glucose levels and reducing ca... more The management of type 2 diabetes (T2D) involves decreasing plasma glucose levels and reducing cardiovascular and microvascular complications. Diabetic kidney disease (DKD), defined as presence of albuminuria, impaired glomerular filtration, or both, is an insidious microvascular complication of diabetes that generates a substantial personal and clinical burden. The progressive reduction in renal function and increased albuminuria results in an increase of cardiovascular events. Thus, patients with DKD require exhaustive control of the associated cardiovascular risk factors. People with diabetes and renal impairment have fewer options of antidiabetic drugs because of contraindications, adverse effects, or altered pharmacokinetics. Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) reduce blood glucose concentrations by blocking the uptake of sodium and glucose in the proximal tubule and promoting glycosuria, and these agents now have an important role in the management of T2D. The results of several cardiovascular outcomes trials suggested that SGLT2i are associated with improvements in renal endpoints in addition to their reduction in cardiovascular events and mortality, which represents a major advance in the care of this population. The dedicated kidney outcomes trials have confirmed the renoprotective action of SGLT2i across different glomerular filtration and albuminuria values, even in patients with non-diabetic chronic kidney disease. Notably, this improvement in kidney function may indirectly All authors have equally participated in the development of the manuscript.

Drugs in Context, 2022

Background: This study aims to evaluate dapagliflozin in patients with type 2 diabetes (T2D) in c... more Background: This study aims to evaluate dapagliflozin in patients with type 2 diabetes (T2D) in clinical practice in Spain. Methods: This is a retrospective study including adults with T2D under stable antidiabetic therapy, with either dapagliflozin or sitagliptin ≥6 months, before inclusion. Data about the effectiveness and safety of dapagliflozin are presented. Results: A total of 594 patients (61.8±9.9 years, 21.7% cardiovascular disease) were included. After 6 months, HbA1c, weight, blood pressure, urine albumin-to-creatinine ratio and uric acid significantly decreased (1.63%, 2.88 kg, 4.82/2.70 mmHg, −17.38 mg/g and −0.30 mg/dL, respectively), whereas glomerular filtration rate and haematocrit significantly increased (3.72 mL/min/1.73 m 2 and 1.8%, respectively). No cases of hypoglycaemia, diabetic ketoacidosis, Fournier gangrene, fractures or amputations were reported. Conclusion: Thus, dapagliflozin provides a comprehensive cardiometabolic protection in patients with T2D.

Revista Colombiana de Cardiología, 2020

Resumen Introducción: la diabetes y la insuficiencia cardiaca son dos enfermedades altamente prev... more Resumen Introducción: la diabetes y la insuficiencia cardiaca son dos enfermedades altamente prevalentes. Desde 1972 existen publicaciones que demuestran cómo los pacientes con diabetes pueden desarrollar insuficiencia cardiaca, independiente de la presencia de otras causas, como la enfermedad coronaria o la hipertensión. Objetivo: realizar una revisión sistemática de la literatura sobre la cardiopatía diabética. Metodología: se utilizaron los términos MESH diabetes e insuficiencia cardiaca y se consultó la base de datos PUBMED. Finalmente, se incluyeron los artículos publicados en inglés y español. Resultados: la cardiopatía diabética es una enfermedad que ocurre como consecuencia de la hiperinsulinemia y la hiperglicemia. Los mecanismos fisiopatológicos que la originan son los cambios metabólicos en la célula miocárdica que generan oxidación, apoptosis y necrosis. Puede manifestarse como fenotipo dilatado o restrictivo. Los inhibidores del cotransportador de sodio glucosa tipo 2 (I-SGLT2) podrían tener un efecto benéfico en el tratamiento de la enfermedad. Conclusión: la cardiopatía diabética es una de las consecuencias de la diabetes mal controlada. Esta relación entre ambas enfermedades resalta la importancia de tratar adecuadamente la diabetes para prevenir el desarrollo de insuficiencia cardiaca.

Diabetic Medicine, 2018

What's new?  This multicentre real-world study is the first using innovative generalized additiv... more What's new?  This multicentre real-world study is the first using innovative generalized additive mixed models (GAMMs) to predict HbA 1c and weight responses upon liraglutide treatment.  GAMMS demonstrated that higher baseline HbA 1c , longer diabetes duration and the use of insulin predicted a worse response on HbA 1c reduction, whereas longer time of treatment with liraglutide predicted a better response. Higher baseline weight, longer time of treatment with liraglutide and the use of metformin predicted a better response on weight reduction. The previous use of dipeptidyl peptidase (DPP)-4 inhibitors did not influence the change in either HbA 1c or weight.  The results reported here will help in understanding the liraglutide response, i.e. how to optimize its management to improve clinical outcomes.

Diabetes, Obesity and Metabolism, 2020

Aim: To evaluate the effectiveness and safety of initiating basal insulin-supported oral therapy ... more Aim: To evaluate the effectiveness and safety of initiating basal insulin-supported oral therapy (BOT) with insulin glargine 300 U/mL (Gla-300) in patients with type 2 diabetes inadequately controlled on oral antidiabetic drugs (OADs). Materials and Methods: This non-interventional, multi-centre, prospective 52-week study, conducted in Germany and Switzerland, documented patients with type 2 diabetes with an HbA1c of between 7.5% and 10.0%, currently treated with OADs, after the physician had decided to start a BOT regimen with Gla-300. The primary endpoint was the rate of achievement of the individualized predefined HbA1c target. Results: Of 1748 patients included, 1153 comprised the full analysis set, of whom 721 completed documentation of 12 months of Gla-300 treatment. Twelve months after starting Gla-300, 49.9% achieved their individualized HbA1c target, and 61.1% achieved either their HbA1c target or a fasting plasma glucose (FPG) of ≤110 mg/dL. Mean HbA1c decreased by −1.22% ± 1.05% to 7.28% ± 0.92% and mean FPG by −51.5 (±48.63) mg/dl to 132.9 ± 33.0 mg/dL. Median duration of HbA1c target achievement was 341 days and probability to remain on target after 6 months was 81%. Hypoglycaemia incidence and rates remained low after 12 months of Gla-300 treatment; no severe or severe nocturnal hypoglycaemia was observed. Body weight remained unchanged. Conclusions: Starting a BOT regimen with Gla-300 allowed about 60% of 721 German and Swiss patients with inadequately controlled type 2 diabetes to achieve glycaemic control within 12 months in daily clinical practice. Glycaemic control was achieved without weight gain or increased risk of nocturnal or severe hypoglycaemia.

Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy

To extend a prior real-world analysis (DARWIN-T2D) of patients with type 2 diabetes initiating da... more To extend a prior real-world analysis (DARWIN-T2D) of patients with type 2 diabetes initiating dapagliflozin in Italy, Greece, and Spain by evaluating changes in glycemic and extra-glycemic endpoints after initiation of dapagliflozin. Patients and Methods: The association among demographic/clinical characteristics and the change in glycemic and extraglycemic effectiveness endpoints during the observation period was assayed using a mixed effects model. Results: A total of 1438 (860 males; 59.8%) patients were evaluated; patients were followed for a mean of 5.6 months. At baseline, 93.4% and 61.9% of patients were on concomitant metformin and insulin, respectively. A significant mean decrease in HbA1c from 8.7% to 7.5% was observed. The mixed model used also revealed several associations between different glycemic and laboratory parameters and patient characteristics at baseline; insulin use was significantly associated with lower HbA1c. Patients with BMI ≥30 kg/m 2 experienced greater weight loss than those with BMI <30 kg/m 2. A consistent glucose-lowering effect of dapagliflozin was seen in all subgroups of patients, including those with stage 2 renal impairment and cardiovascular disease. Conclusion: The present analysis confirms the efficacy of dapagliflozin in diversified real-world settings with broadly similar effects on HbA1c across countries and baseline characteristics.

Value in Health, 2014

A343 infant in comparison to no-screening strategy. Transferred to the entire birth cohort newbor... more A343 infant in comparison to no-screening strategy. Transferred to the entire birth cohort newborn screening is able to reduce total costs by 14 million € from the Austrian health care systems perspective each year. ConClusions: Funding the newborn screening saves money and is cost-effective for the Austrian health care system.

Diabetes therapy : research, treatment and education of diabetes and related disorders, 2017

The incorrect statement in Fig. 2 ''BP\140/ 80 mmHg, aged older than 65 years or hemodynamically ... more The incorrect statement in Fig. 2 ''BP\140/ 80 mmHg, aged older than 65 years or hemodynamically unstable*?'' should read as ''BP\140/80 mmHg, aged older than 65 years or hemodynamically unstable**?'' The incorrect statement in Fig. 2 ''Reintroduce treatment according to clinical situation**?'' should read as ''Reintroduce treatment according to clinical situation***?'' The online version of the original article can be found under

Patient Preference and Adherence, 2015

Objective: To assess Spanish and Portuguese patients' and physicians' preferences regarding type ... more Objective: To assess Spanish and Portuguese patients' and physicians' preferences regarding type 2 diabetes mellitus (T2DM) treatments and the monthly willingness to pay (WTP) to gain benefits or avoid side effects. Methods: An observational, multicenter, exploratory study focused on routine clinical practice in Spain and Portugal. Physicians were recruited from multiple hospitals and outpatient clinics, while patients were recruited from eleven centers operating in the public health care system in different autonomous communities in Spain and Portugal. Preferences were measured via a discrete choice experiment by rating multiple T2DM medication attributes. Data were analyzed using the conditional logit model. Results: Three-hundred and thirty (n=330) patients (49.7% female; mean age 62.4 [SD: 10.3] years, mean T2DM duration 13.9 [8.2] years, mean body mass index 32.5 [6.8] kg/m 2 , 41.8% received oral + injected medication, 40.3% received oral, and 17.6% injected treatments) and 221 physicians from Spain and Portugal (62% female; mean age 41.9 [SD: 10.5] years, 33.5% endocrinologists, 66.5% primary-care doctors) participated. Patients valued avoiding a gain in bodyweight of 3 kg/6 months (WTP: €68.14 [95% confidence interval: 54.55-85.08]) the most, followed by avoiding one hypoglycemic event/month (WTP: €54.80 [23.29-82.26]). Physicians valued avoiding one hypoglycemia/week (WTP: €287.18 [95% confidence interval: 160.31-1,387.21]) the most, followed by avoiding a 3 kg/6 months gain in bodyweight and decreasing cardiovascular risk (WTP: €166.87 [88.63-843.09] and €154.30 [98.13-434.19], respectively). Physicians and patients were willing to pay €125.92 (73.30-622.75) and €24.28 (18.41-30.31), respectively, to avoid a 1% increase in glycated hemoglobin, and €143.30 (73.39-543.62) and €42.74 (23.89-61.77) to avoid nausea. Conclusion: Both patients and physicians in Spain and Portugal are willing to pay for the health benefits associated with improved diabetes treatment, the most important being to avoid hypoglycemia and gaining weight. Decreased cardiovascular risk and weight reduction became the third most valued attributes for physicians and patients, respectively.

Supplementary Table 1. DAPA-RWE: a retrospective multicenter study comparing d... more Supplementary Table 1. DAPA-RWE: a retrospective multicenter study comparing dapagliflozin and sitagliptin in patients with Type 2 diabetes treated under routine clinical practice in Spain. Abstract Background: Weight reduction and glycemic control are key goals during Type 2 diabetes (T2D) management. However, there are few country-specific, real-world data on cotransporter 2 inhibitors. Methods: DAPA-RWE was a retrospective, multicenter study comparing the efficacy of dapagliflozin versus sitagliptin in T2D patients in Spain. Results: The study population comprised 1,046 patients (594 with dapagliflozin, 452 with sitagliptin). Age was 61.8±10.0 and 66.2±11.4 years and HbA1c 8.9 and 8.8%, respectively. The main end point (reduction in weight and HbA1c) was reached by 24.4 and 56.1% of patients, respectively; p < 0.05. This was confirmed with a propensity score matching analysis balanced for obesity-related variables at baseline. Conclusions: DAPA-RWE confirmed dapagliflozin to be more effective than sitagliptin in reducing HbA1c and weight.

Supplementary Table S2. DAPA-RWE: a retrospective multicenter study comparing ... more Supplementary Table S2. DAPA-RWE: a retrospective multicenter study comparing dapagliflozin and sitagliptin in patients with Type 2 diabetes treated under routine clinical practice in Spain. Abstract Background: Weight reduction and glycemic control are key goals during Type 2 diabetes (T2D) management. However, there are few country-specific, real-world data on cotransporter 2 inhibitors. Methods: DAPA-RWE was a retrospective, multicenter study comparing the efficacy of dapagliflozin versus sitagliptin in T2D patients in Spain. Results: The study population comprised 1,046 patients (594 with dapagliflozin, 452 with sitagliptin). Age was 61.8±10.0 and 66.2±11.4 years and HbA1c 8.9 and 8.8%, respectively. The main end point (reduction in weight and HbA1c) was reached by 24.4 and 56.1% of patients, respectively; p < 0.05. This was confirmed with a propensity score matching analysis balanced for obesity-related variables at baseline. Conclusions: DAPA-RWE confirmed dapagliflozin to be more effective than sitagliptin in reducing HbA1c and weight.

Journal of Comparative Effectiveness Research

Background: Weight reduction and glycemic control are key goals during Type 2 diabetes management... more Background: Weight reduction and glycemic control are key goals during Type 2 diabetes management. However, there are few country-specific, real-world data on cotransporter 2 inhibitors. Materials & methods: DAPA-RWE was a retrospective, multicenter study comparing the efficacy of dapagliflozin versus sitagliptin in Type 2 diabetes patients in Spain. Results: The study population comprised 1046 patients (594 with dapagliflozin, 452 with sitagliptin). Age was 61.8 ± 10.0 and 66.2 ± 11.4 years and glycosylated hemoglobin (HbA1c) 8.9 and 8.8%, respectively. The main end point (reduction in weight and HbA1c) was reached by 24.4 and 56.1% of patients, respectively; p

Introduction: Currently self-glycemic control by the patient is essential to achieve a right meta... more Introduction: Currently self-glycemic control by the patient is essential to achieve a right metabolic control of diabetes. Nowadays, there are different systems that have proved useful for this aim. ... Objectives: Valuing any possible differences between systems and the relation ...

... Juan Manuel Garcia-Quiros, Cristobal Morales, Silvia Maraver, Guillermo Martinez de Pinillos,... more ... Juan Manuel Garcia-Quiros, Cristobal Morales, Silvia Maraver, Guillermo Martinez de Pinillos, Monica Tome, Carmen Cuesta, JM Guerrero & Angel Sendon. ... The NB studied were selected by measuring TSH levels in heel dry blood from the provinces of Cadiz, Huelva and ...

The Lancet Diabetes & Endocrinology

BACKGROUND Type 1 diabetes is characterised by progressive loss of functional β-cell mass, necess... more BACKGROUND Type 1 diabetes is characterised by progressive loss of functional β-cell mass, necessitating insulin treatment. We aimed to investigate the hypothesis that combining anti-interleukin (IL)-21 antibody (for low-grade and transient immunomodulation) with liraglutide (to improve β-cell function) could enable β-cell survival with a reduced risk of complications compared with traditional immunomodulation. METHODS This randomised, parallel-group, placebo-controlled, double-dummy, double-blind, phase 2 trial was done at 94 sites (university hospitals and medical centres) in 17 countries. Eligible participants were adults aged 18-45 years with recently diagnosed type 1 diabetes and residual β-cell function. Individuals with unstable type 1 diabetes (defined by an episode of severe diabetic ketoacidosis within 2 weeks of enrolment) or active or latent chronic infections were excluded. Participants were randomly assigned (1:1:1:1), with stratification by baseline stimulated peak C-peptide concentration (mixed-meal tolerance test [MMTT]), to the combination of anti-IL-21 and liraglutide, anti-IL-21 alone, liraglutide alone, or placebo, all as an adjunct to insulin. Investigators, participants, and funder personnel were masked throughout the treatment period. The primary outcome was the change in MMTT-stimulated C-peptide concentration at week 54 (end of treatment) relative to baseline, measured via the area under the concentration-time curve (AUC) over a 4 h period for the full analysis set (intention-to-treat population consisting of all participants who were randomly assigned). After treatment cessation, participants were followed up for an additional 26-week off-treatment observation period. This trial is registered with ClinicalTrials.gov, NCT02443155. FINDINGS Between Nov 10, 2015, and Feb 27, 2019, 553 adults were assessed for eligibility, of whom 308 were randomly assigned to receive either anti-IL-21 plus liraglutide, anti-IL-21, liraglutide, or placebo (77 assigned to each group). Compared with placebo (ratio to baseline 0·61, 39% decrease), the decrease in MMTT-stimulated C-peptide concentration from baseline to week 54 was significantly smaller with combination treatment (0·90, 10% decrease; estimated treatment ratio 1·48, 95% CI 1·16-1·89; p=0·0017), but not with anti-IL-21 alone (1·23, 0·97-1·57; p=0·093) or liraglutide alone (1·12, 0·87-1·42; p=0·38). Despite greater insulin use in the placebo group, the decrease in HbA1c (a key secondary outcome) at week 54 was greater with all active treatments (-0·50 percentage points) than with placebo (-0·10 percentage points), although the differences versus placebo were not significant. The effects diminished upon treatment cessation. Changes in immune cell subsets across groups were transient and mild (<10% change over time). The most frequently reported adverse events included gastrointestinal disorders, in keeping with the known side-effect profile of liraglutide. The rate of hypoglycaemic events did not differ significantly between active treatment groups and placebo, with an exception of a lower rate in the liraglutide group than in the placebo group during the treatment period. No events of diabetic ketoacidosis were observed. One participant died while on liraglutide (considered unlikely to be related to trial treatment) in connection with three reported adverse events (hypoglycaemic coma, pneumonia, and brain oedema). INTERPRETATION The combination of anti-IL-21 and liraglutide could preserve β-cell function in recently diagnosed type 1 diabetes. The efficacy of this combination appears to be similar to that seen in trials of other disease-modifying interventions in type 1 diabetes, but with a seemingly better safety profile. Efficacy and safety should be further evaluated in a phase 3 trial programme. FUNDING Novo Nordisk.

Diabetes

Background and Aims: “T-Coach® program” is a telephone support platform for type 2 diabetes (T2D)... more Background and Aims: “T-Coach® program” is a telephone support platform for type 2 diabetes (T2D) on glargine U300 insulin. This study aimed to evaluate whether this program was effective in helping patients reach their optimal insulin dose. Materials and Methods: Both T2D patients who were initiating glargine U300 or requiring dose titration, enrolled in T-Coach® program, were included in the study. Telephone intervention was delivered by diabetes nurse educators and consisted of regular telephone sessions, aimed at achievement of target fasting blood glucose (FBG) and reinforce diabetes education. The optimal insulin dose (OID) was defined as the dose of Glargine U300 required to achieve target FBG. The primary outcome was whether a patient reached the OID dose within 6 months. Results: A total of 589 patients consented and were included in TCoach program®. Median age was 65.4±11.2 years; 51.8% men; BMI 30.3±6 kg/m2. Of them, 65.9% were already on basal insulin (17.7% on Glargine ...

Diabetes

Dyslipidemia is commonly found in T1D adults and increases the risk of CVD. There is no research ... more Dyslipidemia is commonly found in T1D adults and increases the risk of CVD. There is no research on dyslipidemia in T1D adults in Spain so far. The aim of the study was to evaluate the prevalence and the pattern of dyslipidemia and its relationship with other risk factors or comorbidities. Methods: A multicentric, cross-sectional study in Spain included 1252 adults with T1D who visited Diabetes Clinic from December 2017 to December 2018. Cut-off points for abnormal lipid levels (total cholesterol (TC) ≥200 mg/dL, LDL ≥130 mg/dL, HDL ≤35 mg/dL, and triglycerides (TG) ≥150 mg/dL) were taken from the Third Report of the National Cholesterol Education Program and the ADA. Dyslipidemia was defined by the presence of one or more abnormal serum lipid concentrations. Results: Among 1252 patients 50,3% were male. Median age 40,5+/-13 years old and the median duration of diabetes was 20+/-13 years. Median A1c 7,96+/-2,49% and BMI 25,7+/-4,6kg/m2 The overall lipid profile was TC 188+/-42 mg/dL...

Revista Colombiana de Nefrología

Diabetes Therapy

Drugs in Context, 2022

Revista Colombiana de Cardiología, 2020

Diabetic Medicine, 2018

Diabetes, Obesity and Metabolism, 2020

Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy

Value in Health, 2014

Diabetes therapy : research, treatment and education of diabetes and related disorders, 2017

Patient Preference and Adherence, 2015

Journal of Comparative Effectiveness Research

The Lancet Diabetes & Endocrinology

Diabetes