GLP1 Receptor Agonist and SGLT2 Inhibitor Combination: An Effective Approach in Real-world Clinical Practice.

PURPOSE: The aim of this study was to evaluate the effectiveness and safety of combination therapy with a sodium-glucose cotransporter-2 (SGLT2) inhibitor and a glucagon-like peptide-1 receptor agonist (GLP1RA) in patients with inadequately controlled type 2 diabetes. METHODS: A retrospective search of electronic prescriptions of patients undergoing GLP1RA and SGLT2 inhibitor combination therapy was conducted. Once the patients had been identified, demographic data, blood and urine analyses (glycosylated hemoglobin [HbA1c], glucose, renal function, albuminuria, lipid profile, liver enzymes, and uric acid), physical examination (weight, body mass index, and blood pressure), and adverse effects were obtained from their electronic clinical records according to each of the following 3 periods: before the initiation of the combination, the first visit after initiation, and the last available visit. The influence of the duration of diabetes and the drug combination sequence on the effectiveness of the treatment was also analyzed. Statistical analysis was performed with SPSS version 21.0 (IBM SPSS Statistics, IBM Corporation, Armonk, New York). Quantitative variables are presented as mean and SD and were compared by using the Student t test, one-way ANOVA, or repeated measures ANOVA with Bonferroni correction. Categorical variables are expressed as percentages and were compared by using the χ2 test. RESULTS: A total of 212 patients were included, with women accounting for 52.4%. The mean age (SD) of the population was 61.5 (9.6) years. A significant reduction in HbA1c (-12 mmol/mol [-1.1%]) was observed with combined therapy (P < 0.001). The target of HbA1c <53 mmol/mol (<7%) was achieved in 42% of the participants. Mean weight loss was -3.5 kg, and almost 40% of the patients attained the weight loss goal of ≥5% (P < 0.001 in all analyses). Transaminase levels and renal parameters also improved. These benefits persisted over time and bore no relation to the evolution of diabetes. Simultaneous initiation of a combination of a GLP1RA and SGLT2 inhibitor led to faster weight loss and a greater decrease in HbA1c than when they are used sequentially; however, the long-term benefits in terms of metabolic control were similar. Adverse events were rare, and a tendency for a reduced insulin dose was observed. IMPLICATIONS: The findings of this study reveal the combined benefits of a GLP1RA and SGLT2 inhibitor in real-world clinical practice. In general, the combined treatment was well tolerated, and few adverse events were detected.

Documento de consenso del área de conocimiento de Neuroendocrinología de la Sociedad Española de Endocrinología y Nutrición para el abordaje del hipopituitarismo durante la transición / Consensus document of the Neuroendocrinology area of the Spanish Society of Endocrinology and Nutrition on management of hypopituitarism during transition

Se entiende por periodo de transición del niño al adulto a una etapa de cambios físicos y psicológicos que, de forma arbitraria, se extiende desde el final de la pubertad hasta que la maduración adulta se completa. Comprende, habitualmente, los 6 a 7 años posteriores al momento en que el niño adquiere la talla adulta. Con esta documento pretendemos poner de manifiesto la importancia de la adecuada sustitución de los diferentes déficits hipotálamo-hipofisarios durante este período. Para ello revisamos la reevaluación del status hipofisario en los pacientes deficitarios durante la infancia, tratamos de dar respuesta a las preguntas que pueden surgir y ofrecemos unas recomendaciones claras de cómo abordar la deficiencia de GH en este período. Posteriormente abordamos también la evaluación y la sustitución del eje adrenal, tiroideo y gonadal

The transition period from child to adult represents a crucial phase in the growth process where multiple physical and psychosocial changes occur. It has been arbitrarily defined as the period extending from late puberty to full adult maturity (i.e., from mid to late teenage years until 6-7 years after achievement of final height).The aim of this guideline is to emphasize the importance of adequate hormone replacement during this period and to review reassessment of pituitary function. In patients with GH deficiency diagnosed in childhood, an attempt is made to answer when to retest GH secretion, when to treat and how they should be monitored. Thyroxine, glucocorticoid, and sex steroid replacement are also reviewed

Consensus document of the Neuroendocrinology area of the Spanish Society of Endocrinology and Nutrition on management of hypopituitarism during transition.

The transition period from child to adult represents a crucial phase in the growth process where multiple physical and psychosocial changes occur. It has been arbitrarily defined as the period extending from late puberty to full adult maturity (i.e., from mid to late teenage years until 6-7 years after achievement of final height). The aim of this guideline is to emphasize the importance of adequate hormone replacement during this period and to review reassessment of pituitary function. In patients with GH deficiency diagnosed in childhood, an attempt is made to answer when to retest GH secretion, when to treat and how they should be monitored. Thyroxine, glucocorticoid, and sex steroid replacement are also reviewed.

Estudio clínico y molecular de cinco familias con resistencia a la acción de las hormonas tiroideas / Clinical and molecular study of five families with resistance to thyroid hormones

Fundamento y objetivo: La resistencia a la acción de las hormonas tiroideas (SRHT) es un síndrome causado mayoritariamente por mutaciones en el gen receptor beta de las hormonas tiroideas (THRB). Se estudian cinco familias con fenotipo de SRHT. Pacientes y método: Se realizó secuenciación de THRB. Se evaluó la respuesta a triyodotironina (T3) y efecto dominante negativo de los mutantes in vitro y se estudiaron los mecanismos de resistencia en sujetos sin mutación THRB cuantificando en cultivos de fibroblastos cambios de expresión en los genes regulator of calcineurin 2 (ZAKI4) y Kruppel-like factor 9 (BTEB). Resultados: Tres casos presentaron mutaciones en THRB: R243Q, R320C, R429Q, dando lugar a receptores TRβ con menor respuesta a T3. R243Q y R320C ejercen efecto dominante negativo. Un sujeto sin mutación THRB presentó cambios de expresión en ZAKI4 y BTEB similar a R230C, mientras que el otro mostró niveles de expresión superiores a los controles. Conclusiones: Mutaciones heterocigotas en THRB causaron tres de los casos de SRHT estudiados. Uno de los casos con SRHT sin mutación se comporta a nivel molecular como los portadores de mutación, mientras que en el otro la resistencia no está mediada por TRβ (AU)

Background and objective: Resistance to thyroid hormone (RTH) is a syndrome mostly caused by mutations in thyroid hormone receptor beta gen (THRB). We present five families with RTH phenotype. Patients and methods:THRB gene sequencing. In vitro studies to evaluate the mutants response to thyroid hormones and their dominant negative effect. Mechanism of resistance in patients with RTH without THRB mutations quantifying expression of regulator of calcineurin 2 (ZAKI4) and Kruppel-like factor 9 (BTEB) genes in patients fibroblast cultures.Results: THRB mutations were found in three cases: R243Q, R320C, R429Q. Mutants showed a decreased response to T3. R243Q and R320C had a strong dominant negative effect. One subject without THRB mutation showed changes in ZAKI4 and BTEB expression similar to R320C and the other showed expression levels higher than normal controls. Conclusions:Three cases of RTH were caused by THRB heterozygous mutations but in two cases mutations were not found. THRB mutation carriers and one of the patients without mutations share a similar mechanism of resistance and in the other subject RTH is TRβ independent (AU)

[Clinical and molecular study of five families with resistance to thyroid hormones]. / Estudio clínico y molecular de cinco familias con resistencia a la acción de las hormonas tiroideas.

BACKGROUND AND OBJECTIVE: Resistance to thyroid hormone (RTH) is a syndrome mostly caused by mutations in thyroid hormone receptor beta gen (THRB). We present five families with RTH phenotype. PATIENTS AND METHODS: THRB gene sequencing. In vitro studies to evaluate the mutants response to thyroid hormones and their dominant negative effect. Mechanism of resistance in patients with RTH without THRB mutations quantifying expression of regulator of calcineurin 2 (ZAKI4) and Kruppel-like factor 9 (BTEB) genes in patients fibroblast cultures. RESULTS: THRB mutations were found in three cases: R243Q, R320C, R429Q. Mutants showed a decreased response to T3. R243Q and R320C had a strong dominant negative effect. One subject without THRB mutation showed changes in ZAKI4 and BTEB expression similar to R320C and the other showed expression levels higher than normal controls. CONCLUSIONS: Three cases of RTH were caused by THRB heterozygous mutations but in two cases mutations were not found. THRB mutation carriers and one of the patients without mutations share a similar mechanism of resistance and in the other subject RTH is TRß independent.