Use of Tirzepatide in Adults with Type 2 Diabetes Mellitus: Scientific Evidence and Practical Aspects.

Tirzepatide is a novel antidiabetic medication a single-molecule, agonist to the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors. It is approved in the USA and EU for the treatment of type 2 diabetes mellitus (T2DM) and obesity. Due to the potential novelty represented by incorporating tirzepatide to clinical practice, we aim to review practical aspects of tirzepatide use in T2DM and the supporting scientific evidence. A group of ten endocrinologists involved as investigators in the phase 3 SURPASS clinical trial program followed a nominal group technique, a qualitative research methodology designed as a semi-structured group discussion to reach a consensus on the selection of a set of practical aspects. The scientific evidence for tirzepatide has been reviewed with respect to a number of patients' clinical profiles and care goals. Information of interest related to adverse events, special warnings and precautions, and other considerations for tirzepatide use has been included. Finally, information provided to the patients has been summarized. The practical aspects reported herein may be helpful in guiding physicians in the use of tirzepatide and contribute to optimizing the management of T2DM.

Reduction of prevalence of patients meeting the criteria for metabolic syndrome with tirzepatide: a post hoc analysis from the SURPASS Clinical Trial Program.

BACKGROUND: Metabolic syndrome is characterized as the co-occurrence of interrelated cardiovascular risk factors, including insulin resistance, hyperinsulinemia, abdominal obesity, dyslipidemia and hypertension. Once weekly tirzepatide is approved in the US and EU for the treatment of type 2 diabetes (T2D) and obesity. In the SURPASS clinical trial program for T2D, tirzepatide demonstrated greater improvements in glycemic control, body weight reduction and other cardiometabolic risk factors versus placebo, subcutaneous semaglutide 1 mg, insulin degludec, and insulin glargine. This post hoc analysis assessed the effect of tirzepatide use on the prevalence of patients meeting the criteria for metabolic syndrome across SURPASS 1-5. METHODS: Metabolic syndrome was defined as having ≥ 3 of 5 criteria according to the US National Cholesterol Education Program: Adult Treatment Panel III. Analyses were based on on-treatment data at the primary endpoint from patients adherent to treatment (taking ≥ 75% study drug). A logistic regression model with metabolic syndrome status as the response variable, metabolic syndrome status at the baseline visit as an adjustment, and randomized treatment as fixed explanatory effect was used. The effect of tirzepatide use on the prevalence of patients meeting the criteria for metabolic syndrome by categorical weight loss, background medication and gender were assessed. RESULTS: In SURPASS, the prevalence of patients meeting the criteria for metabolic syndrome at baseline was 67-88% across treatment groups with reductions at the primary endpoint to 38-64% with tirzepatide versus 64-82% with comparators. Reductions in the prevalence of patients meeting the criteria for metabolic syndrome was significantly greater with all tirzepatide doses versus placebo, semaglutide 1 mg, insulin glargine, and insulin degludec (p < 0.001). Individual components of metabolic syndrome were also reduced to a greater extent with tirzepatide vs comparators. Greater reductions in body weight were associated with greater reductions in the prevalence of patients meeting the criteria for metabolic syndrome and its individual components. Background SGLT2i or sulfonylurea use or gender did not impact the change in prevalence of patients meeting the criteria for metabolic syndrome. CONCLUSIONS: In this post hoc analysis, tirzepatide at all doses studied was associated with a greater reduction in the prevalence of patients meeting the criteria for metabolic syndrome compared to placebo, semaglutide 1 mg, insulin degludec, and insulin glargine. Although more evidence is needed, these data would support greater potential improvement in cardiovascular risk factor profile with tirzepatide treatment in people across the continuum of T2D.

Eficacia y seguridad de empagliflozina en combinación con otros hipoglucemiantes orales en pacientes con diabetes mellitus tipo 2 / Efficacy and safety of empagliflozin in combination with other oral hypoglycemic agents in patients with type 2 diabetes mellitus

Introducción: Analizar la eficacia y la seguridad de empagliflozina en combinación con otros hipoglucemiantes orales en pacientes con diabetes mellitus tipo 2. Métodos: Análisis de 3 ensayos fase III en pacientes con diabetes mellitus tipo 2 (n=1.801) que recibieron placebo, empagliflozina 10 o 25mg, una vez al día, durante 24 semanas, en combinación con metformina, metformina+sulfonilurea o pioglitazona±metformina. Resultados: Empagliflozina redujo significativamente la HbA1c (reducción media ajustada vs. placebo con empagliflozina 10 mg: -0,58% [IC 95%: -0,66; -0,49]; p < 0,0001 y con empagliflozina 25 mg -0,62% [IC 95%: -0,70; -0,53], p<0,0001), el peso (reducción media ajustada vs. placebo con empagliflozina 10 mg: -1,77kg [IC 95%: -2,05; -1,48]; p < 0,0001 y con empagliflozina 25 mg: -1,96 kg [IC 95%: -2,24; -1,67], p < 0,0001) y la presión arterial sistólica y diastólica. La frecuencia de efectos adversos fue del 64% con placebo, del 63,9% con empagliflozina 10 mg y del 60,9% con empagliflozina 25 mg. Las hipoglucemias confirmadas (menor o igual a 70 mg/dl y/o requiriendo asistencia) ocurrieron en un 3,9% de los pacientes con placebo, un 6,9% con empagliflozina 10 mg y un 5,3% con empagliflozina 25 mg. Las infecciones del tracto urinario acontecieron en un 9,4% con placebo, un 10,2% con empagliflozina 10 mg y un 8,3% con empagliflozina 25 mg. Las infecciones genitales se comunicaron en un 1,0% de los pacientes con placebo, un 4,6% con empagliflozina 10 mg y un 3,5% con empagliflozina 25 mg. Conclusiones: Empagliflozina en combinación con otros tratamientos orales vs. placebo disminuyó significativamente la HbA1c, el peso corporal y la presión arterial sistólica/diastólica, con un buen perfil de seguridad y tolerancia (AU)

Introduction: To analyze the efficacy and safety of empagliflozin combined with other oral hypoglycemic agents in patients with type 2 diabetes mellitus. Methods: Pooled analysis of three phase III trials in patients with type 2 diabetes mellitus (n=1,801) who received placebo or empagliflozin 10 or 25 mg once daily for 24 weeks, in combination with metformin, metformin+sulphonylurea or pioglitazone ± metformin. Results: Empagliflozin significantly decreased HbA1c (adjusted mean reduction vs placebo with empagliflozin 10mg: -0.58% [95% CI: -0.66; -0.49]; P<.0001, and with empagliflozin 25 mg: -0.62% [95% CI: -0.70; -0.53], P<.0001), weight (adjusted mean reduction vs placebo with empagliflozin 10 mg: -1.77 kg [95% CI: -2.05; -1.48]; P <.0001, and with empagliflozin 25mg: -1.96kg [95% CI: -2.24; -1.67], P<.0001), and systolic and diastolic blood pressure (SBP/DBP). Adverse effect rates were 64% with placebo, 63.9% with empagliflozin 10 mg, and 60.9% with empagliflozin 25 mg. Documented episodes of hypoglycemia (is less than or equal to 70 mg/dL and/or requiring care) occurred in 3.9% of patients with placebo, 6.9% of patients with empagliflozin 10 mg, and 5.3% of patients with empagliflozin 25 mg. Urinary tract infections developed in 9.4% of patients with placebo, 10.2% of patients with empagliflozin 10 mg, and 8.3% of patients with empagliflozin 25 mg. Genital infections were reported in 1.0% of patients with placebo, 4.6% of patients with empagliflozin 10mg, and 3.5% of patients with empagliflozin 25 mg. Conclusions: Empagliflozin combined with other oral treatments decreased HbA1c, body weight, and SBP/DBP as compared to placebo, with a good safety and tolerability profile (AU)

Remisión y funcionalidad en el trastorno depresivo mayor / Remission and functioning in major depressive disorder

La evidencia procedente de numerosos estudios clínicos ha demostrado que el objetivo óptimo en el tratamiento de la depresión es la remisión. La remisión implicaría que los signos y síntomas de la enfermedad estén ausentes o prácticamente ausentes, lo cual se asocia típicamente con una vuelta a la funcionalidad diaria previa del paciente. La funcionalidad en depresión es un concepto amplio, que cubre diferentes dominios, existiendo numerosos instrumentos validados para su valoración que se revisan en este artículo. Asimismo, cada vez más se identifica que la recuperación de la funcionalidad al nivel pre-mórbido es un objetivo significativo adicional a la remisión sintomática. En este sentido, la recuperación de la funcionalidad se ha relacionado con un mejor pronóstico de la depresión, siendo también un objetivo clínico expresado por el paciente. Entre los factores contribuyentes a la recuperación funcional se encuentra la remisión completa de los síntomas, sin síntomas residuales, el mantenimiento de la remisión, calidad de la misma, así como que esta se produzca de una manera temprana. Con el fin de favorecer los resultados clínicos se hace necesaria la integración en la práctica clínica de la evaluación y búsqueda de no sólo la remisión sintomática sino también de la recuperación funcional (AU)

Evidence from numerous clinical studies has shown that the optimal goal for the treatment of depression is remission. Remission implies that the signs and symptoms of the disease are absent or virtually absent, which is typically associated with a return to the patient’s previous daily functioning. Functioning in depression is a broad concept that covers different domains. There are many validated instruments for its assessment, these being reviewed in this article. Furthermore, recovering the pre-morbid level of functioning level is increasingly being identified as a significant target in addition to symptomatic remission. In this sense, functional recovery has been associated with better prognosis of depression and is also a clinical goal expressed by the patient. Several factors, like complete remission of symptoms, with no residual symptoms, maintenance of remission, quality of remission, early remission, have been identified as contributors to functional recovery. In order to facilitate the clinical outcomes, evaluation of and search for symptomatic remission as well as functional recovery need to be integrated into the clinical practice (AU)