RESUMEN
To investigate the safety and efficacy of long-acting glucagon like peptide-1 receptor agonists in overweight or obese patients with type 2 diabetes. Overweight or obese patients with type 2 diabetes from July 2021 to June 2022 were randomly divided into control group (metformin) and experimental group (metformin + dulaglitide or semaglutide). Repeated measures analysis of variance was used to compare Hemoglobin A1c, fasting plasma glucose and body mass index (BMI) of patients before treatment, 6 months and 12 months after treatment. The adverse reactions of patients before treatment and 12 months after treatment were analyzed. The time effect of Hemoglobin A1c, fasting plasma glucose and BMI in the control group (nâ =â 35) and the experimental group (nâ =â 32) were statistically significant (Pâ <â .001), and the intergroup effect of BMI was statistically significant (Pâ <â .05). The interaction effect of BMI was statistically significant (Pâ <â .001). The BMI level of the experimental group was lower than that of the control group at 6 and 12 months after treatment (Pâ <â .001). There was no significant difference in the incidence of adverse reactions between the 2 groups (Pâ >â .05). Long-acting glucagon like peptide-1 receptor agonists, such as dulaglitide and semaglutide, not only reduce glycosylated hemoglobin levels, but also significantly improve BMI in overweight or obese patients with type 2 diabetes.
Asunto(s)
Glucemia , Índice de Masa Corporal , Diabetes Mellitus Tipo 2 , Receptor del Péptido 1 Similar al Glucagón , Péptidos Similares al Glucagón , Hemoglobina Glucada , Hipoglucemiantes , Metformina , Obesidad , Sobrepeso , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Masculino , Persona de Mediana Edad , Femenino , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hipoglucemiantes/uso terapéutico , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/análogos & derivados , Hemoglobina Glucada/efectos de los fármacos , Hemoglobina Glucada/análisis , Obesidad/tratamiento farmacológico , Obesidad/complicaciones , Metformina/uso terapéutico , Sobrepeso/tratamiento farmacológico , Sobrepeso/complicaciones , Glucemia/efectos de los fármacos , Glucemia/análisis , Anciano , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Fragmentos Fc de Inmunoglobulinas/efectos adversos , Análisis de Varianza , Adulto , Quimioterapia Combinada , Agonistas Receptor de Péptidos Similares al Glucagón , Proteínas Recombinantes de FusiónRESUMEN
Obesity is a well-known risk factor for testicular function; however, dulaglutide's effect on the testis in obesity has received little attention. Currently, clinicians prescribe the antidiabetic drug dulaglutide only off-label for weight management in non-diabetics. Investigating the impact of this novel compound on obesity is critical for determining whether it has any disruptive effects on testicular cells. We used a well-known animal model of high-fat diet-induced obesity in this investigation, and testicular dysfunction was determined by sperm DNA damage, spermatocyte chromosomal abnormalities, and spermiogram analysis. Following a 12-week high-fat diet challenge, mice were randomly assigned to dulaglutide (0.6â¯mg/kg/day) or saline treatments for five weeks. Testes and sperm cells were collected 24â¯h after the last dulaglutide injection. Untreated obese mice had a lower testes/body weight ratio, more sperm DNA damage, diakinesis-metaphase I chromosomal abnormalities, a lower sperm count/motility, more cell morphological defects, and an altered testicular redox balance. In obese mice, dulaglutide injection efficiently restored all disturbed parameters to their control levels. Dulaglutide injection into healthy mice exhibited no significant harmful effects at the applied regimen. As a result, we infer that dulaglutide therapy might bring obese men additional benefits by recovering testicular dysfunction induced by obesity.
Asunto(s)
Dieta Alta en Grasa , Modelos Animales de Enfermedad , Péptidos Similares al Glucagón , Fragmentos Fc de Inmunoglobulinas , Obesidad , Proteínas Recombinantes de Fusión , Testículo , Animales , Masculino , Fragmentos Fc de Inmunoglobulinas/farmacología , Obesidad/tratamiento farmacológico , Péptidos Similares al Glucagón/análogos & derivados , Péptidos Similares al Glucagón/farmacología , Péptidos Similares al Glucagón/uso terapéutico , Dieta Alta en Grasa/efectos adversos , Ratones , Proteínas Recombinantes de Fusión/farmacología , Testículo/efectos de los fármacos , Testículo/patología , Testículo/metabolismo , Daño del ADN/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Hipoglucemiantes/farmacología , Motilidad Espermática/efectos de los fármacos , Ratones Endogámicos C57BL , Aberraciones Cromosómicas/efectos de los fármacos , Enfermedades Testiculares/tratamiento farmacológicoAsunto(s)
Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Hipoglucemiantes , Fragmentos Fc de Inmunoglobulinas , Ensayos Clínicos Controlados Aleatorios como Asunto , Proteínas Recombinantes de Fusión , Pérdida de Peso , Humanos , Péptidos Similares al Glucagón/análogos & derivados , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Proteínas Recombinantes de Fusión/uso terapéutico , Proteínas Recombinantes de Fusión/administración & dosificación , Hipoglucemiantes/uso terapéutico , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Fragmentos Fc de Inmunoglobulinas/efectos adversos , Pérdida de Peso/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Resultado del Tratamiento , Ácidos Grasos , PéptidosRESUMEN
AIMS: To describe healthcare resource utilization (HCRU) and associated costs after initiation of injectable glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy by adult patients with type 2 diabetes (T2D) in the prospective, observational, 24-month TROPHIES study in France, Germany, and Italy. MATERIALS AND METHODS: HCRU data for cost calculations were collected by treating physicians during patient interviews at baseline and follow-up visits approximately 6, 12, 18, and 24 months after GLP-1 RA initiation with once-weekly dulaglutide or once-daily liraglutide. Costs were evaluated from the national healthcare system (third-party payer) perspective and updated to 2018 prices. RESULTS: In total, 2,005 patients were eligible for the HCRU analysis (1,014 dulaglutide; 991 liraglutide). Baseline patient characteristics were generally similar between treatment groups and countries. The largest proportions of patients using ≥2 oral glucose-lowering medications (GLMs) at baseline (42.9-43.4%) and month 24 (44.0-45.1%) and using another injectable GLM at month 24 (15.3-23.2%) were in France. Mean numbers of primary and secondary healthcare contacts during each assessment period were highest in France (range = 4.0-10.7) and Germany (range = 2.9-5.7), respectively. The greatest proportions (≥60%) of mean annualized costs per patient comprised medication costs. Mean annualized HCRU costs per patient varied by treatment cohort and country: the highest levels were in the liraglutide cohort in France (909) and the dulaglutide cohort in Germany (883). LIMITATIONS: Limitations included exclusion of patients using insulin at GLP-1 RA initiation and collection of HCRU data by physician, not via patient-completed diaries. CONCLUSIONS: Real-world HCRU and costs associated with the treatment of adults with T2D with two GLP-1 RAs in TROPHIES emphasize the need to avoid generalization with respect to HCRU and costs associated with a particular therapy when estimating the impact of a new treatment in a country-specific setting.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have become frequent treatments of hyperglycemia in type-2 diabetes (T2D). Not all types of clinical study provide information about the cost of these treatments or the effects they might have on use of other medicines and equipment to control T2D or the need for visits to a doctor or nurse and different types of treatment in hospital. This study collected this information during the regular care of adults in France, Germany, or Italy who were prescribed either dulaglutide or liraglutide (both types of GLP-1 RAs) by their family doctor or a specialist in T2D. There were differences in costs and the need for other medicines and medical services between people using either dulaglutide or liraglutide and for people who were using the same GLP-1 RA in each of the three countries. The information from this study could be used to more accurately understand the overall costs and medical care needed when patients use dulaglutide or liraglutide in France, Germany, or Italy.
Asunto(s)
Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Hipoglucemiantes , Fragmentos Fc de Inmunoglobulinas , Liraglutida , Proteínas Recombinantes de Fusión , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/economía , Liraglutida/uso terapéutico , Liraglutida/economía , Péptidos Similares al Glucagón/análogos & derivados , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/economía , Péptidos Similares al Glucagón/administración & dosificación , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Fragmentos Fc de Inmunoglobulinas/economía , Proteínas Recombinantes de Fusión/economía , Proteínas Recombinantes de Fusión/uso terapéutico , Proteínas Recombinantes de Fusión/administración & dosificación , Masculino , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/economía , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Recursos en Salud/estadística & datos numéricos , Recursos en Salud/economía , Modelos EconométricosRESUMEN
Obesity is an established risk factor for numerous malignancies, although it remains uncertain whether the disease itself or weight-loss drugs are responsible for a greater predisposition to cancer. The objective of the current study was to determine the impact of dulaglutide on genetic and epigenetic DNA damage caused by obesity, which is a crucial factor in the development of cancer. Mice were administered a low-fat or high-fat diet for 12 weeks, followed by a 5-week treatment with dulaglutide. Following that, modifications of the DNA bases were examined using the comet assay. To clarify the underlying molecular mechanisms, oxidized and methylated DNA bases, changes in the redox status, levels of inflammatory cytokines, and the expression levels of some DNA repair genes were evaluated. Animals fed a high-fat diet exhibited increased body weights, elevated DNA damage, oxidation of DNA bases, and DNA hypermethylation. In addition, obese mice showed altered inflammatory responses, redox imbalances, and repair gene expressions. The findings demonstrated that dulaglutide does not exhibit genotoxicity in the investigated conditions. Following dulaglutide administration, animals fed a high-fat diet demonstrated low DNA damage, less oxidation and methylation of DNA bases, restored redox balance, and improved inflammatory responses. In addition, dulaglutide treatment restored the upregulated DNMT1, Ogg1, and p53 gene expression. Overall, dulaglutide effectively maintains DNA integrity in obese animals. It reduces oxidative DNA damage and hypermethylation by restoring redox balance, modulating inflammatory responses, and recovering altered gene expressions. These findings demonstrate dulaglutide's expediency in treating obesity and its associated complications.
Asunto(s)
Daño del ADN , Metilación de ADN , Reparación del ADN , Dieta Alta en Grasa , Péptidos Similares al Glucagón , Fragmentos Fc de Inmunoglobulinas , Oxidación-Reducción , Proteínas Recombinantes de Fusión , Animales , Péptidos Similares al Glucagón/análogos & derivados , Péptidos Similares al Glucagón/farmacología , Metilación de ADN/efectos de los fármacos , Fragmentos Fc de Inmunoglobulinas/farmacología , Daño del ADN/efectos de los fármacos , Ratones , Reparación del ADN/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Proteínas Recombinantes de Fusión/farmacología , Masculino , Oxidación-Reducción/efectos de los fármacos , Inflamación/metabolismo , Inflamación/genética , Estrés Oxidativo/efectos de los fármacos , Obesidad/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/genética , Regulación de la Expresión Génica/efectos de los fármacos , Ratones Endogámicos C57BLRESUMEN
AIMS: Package labeling for weight loss formulations of semaglutide and liraglutide include a warning for suicidal thoughts and behaviors. The objective was to examine the association between glucagon-like peptide-1 receptor agonists (GLP-1RA) and incident depression. METHODS: This retrospective cohort study compared Veterans Health Administration patients initiated on a GLP-1RA versus a dipeptidyl peptidase-4 inhibitor (DPP-4i) between June 1, 2013 and June 30, 2020. The primary outcome was incident depression, defined as a new diagnosis of depression or new antidepressant prescription, within 1 year following drug initiation. Multivariable log-binomial regression was used to estimate relative risk, adjusted for confounding factors including patient demographics, comorbid conditions, and prior medication. RESULTS: Of 34,130 patients initiated on a GLP-1RA and 105,478 initiated on a DPP-4i, incident depression occurred in 7.7â¯% (n= 2263) and 6.3â¯% (n= 6602), respectively. After adjustment, the relative risk was 1.02 (95â¯% CI: 0.97 - 1.07), thus failing to demonstrate a significant increase in risk for incident depression following initiation of a GLP-1RA compared to DPP-4i. Relative risk estimates in all sensitivity analyses were also non-significant. CONCLUSIONS: This study did not demonstrate a significant increase in risk for incident depression following GLP-1RA initiation.
Asunto(s)
Depresión , Agonistas Receptor de Péptidos Similares al Glucagón , Hipoglucemiantes , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antidepresivos/efectos adversos , Antidepresivos/uso terapéutico , Depresión/diagnóstico , Depresión/epidemiología , Péptidos Similares al Glucagón/análogos & derivados , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Incidencia , Incretinas/efectos adversos , Incretinas/uso terapéutico , Liraglutida/uso terapéutico , Liraglutida/efectos adversos , Estudios Retrospectivos , Medición de Riesgo , Factores de Tiempo , Estados Unidos/epidemiología , United States Department of Veterans Affairs , Agonistas Receptor de Péptidos Similares al Glucagón/efectos adversos , Agonistas Receptor de Péptidos Similares al Glucagón/uso terapéuticoRESUMEN
AIM: To compare the incidence of adverse events (AEs) related to antiobesity medications (AOMs; glucagon-like peptide-1 receptor agonists [GLP-1RAs] vs. non-GLP-1RAs) after bariatric surgery. METHODS: This single-centre retrospective cohort included patients (aged 16-65 years) who had undergone laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy (cohort entry date) and initiated AOMs. Participants were categorized as users of US Food and Drug Administration (FDA)-approved, off-label, or GLP-1RA AOMs if documented as receiving the medication on or after cohort entry date. Non-GLP-1RA AOMs were phentermine, orlistat, topiramate, canagliflozin, dapagliflozin, empagliflozin, naltrexone, bupropion/naltrexone and phentermine/topiramate. GLP-1RA AOMs included: semaglutide, dulaglutide, exenatide and liraglutide. The primary outcome was AE incidence. Logistic regression was used to determine the association of AOM exposure with AEs. RESULTS: We identified 599 patients meeting our inclusion criteria, 83% of whom were female. Their median (interquartile range [IQR]) age was 47.8 (40.9-55.4) years. The median duration of surgery to AOM exposure was 30 months. GLP-1RAs use was not associated with higher odds of AEs: adjusted odds ratio (aOR) 1.1 (95% confidence interval [CI] 0.5-2.6) and aOR 1.1 (95% CI 0.6-2.3) for GLP-1RA versus FDA-approved and off-label AOM use, respectively. AOM initiation ≥12 months after surgery was associated with lower risk of AEs compared to <12 months (aOR 0.01 [95% CI 0.0-0.01]; p < 0.001). CONCLUSION: Our results showed that GLP-1RA AOMs were not associated with an increased risk of AEs compared to non-GLP-1RA AOMs in patients who had previously undergone bariatric surgery. Prospective studies are needed to identify the optimal timeframe for GLP-1RA initiation.
Asunto(s)
Fármacos Antiobesidad , Cirugía Bariátrica , Receptor del Péptido 1 Similar al Glucagón , Humanos , Femenino , Persona de Mediana Edad , Adulto , Masculino , Receptor del Péptido 1 Similar al Glucagón/agonistas , Estudios Retrospectivos , Fármacos Antiobesidad/uso terapéutico , Fármacos Antiobesidad/efectos adversos , Adulto Joven , Adolescente , Cirugía Bariátrica/efectos adversos , Anciano , Liraglutida/uso terapéutico , Exenatida/uso terapéutico , Obesidad Mórbida/cirugía , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/análogos & derivados , Péptidos Similares al Glucagón/efectos adversos , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Fragmentos Fc de Inmunoglobulinas/efectos adversos , Proteínas Recombinantes de Fusión/uso terapéutico , Proteínas Recombinantes de Fusión/efectos adversos , Agonistas Receptor de Péptidos Similares al GlucagónRESUMEN
Diabetic osteopathy is a frequent complication in patients with type 2 diabetes mellitus (T2DM). The association between T2DM and increased fracture risk has led to study the impact of new antidiabetic drugs on bone metabolism. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin mimetic drugs which have many pleiotropic properties. The relationship between GLP-1RAs and bone is very complex: while in vitro and animal studies have demonstrated a protective effect on bone, human studies are scarce. We led a 12 months longitudinal study evaluating bone changes in 65 patients withT2DM for whom a therapy with GLP-1RAs had been planned. Fifty-four T2DM patients completed the 12-month study period; of them, 30 had been treated with weekly dulaglutide and 24 with weekly semaglutide. One-year therapy with GLP-1RAs resulted in a significant reduction in weight and BMI. Bone mineral density (BMD), bone metabolism, trabecular bone score (TBS), adiponectin, and myostatin were evaluated before and after 12 months of GLP-1RAs therapy. After 12 months of therapy bone turnover markers and adiponectin showed a significant increase, while myostatin values showed a modest but significant reduction. BMD-LS by DXA presented a significant reduction while the reduction in BMD-LS by REMS was not significant and TBS values showed a marginal increase. Both DXA and REMS techniques showed a modest but significant reduction in femoral BMD. In conclusion, the use of GLP-1RAs for 12 months preserves bone quality and reactivates bone turnover. Further studies are needed to confirm whether GLP-1RAs could represent a useful therapeutic option for patients with T2DM and osteoporosis.
Asunto(s)
Densidad Ósea , Diabetes Mellitus Tipo 2 , Receptor del Péptido 1 Similar al Glucagón , Péptidos Similares al Glucagón , Hipoglucemiantes , Fragmentos Fc de Inmunoglobulinas , Incretinas , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Estudios Longitudinales , Receptor del Péptido 1 Similar al Glucagón/agonistas , Femenino , Persona de Mediana Edad , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/análogos & derivados , Péptidos Similares al Glucagón/farmacología , Masculino , Densidad Ósea/efectos de los fármacos , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Anciano , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Incretinas/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Proteínas Recombinantes de Fusión/farmacología , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Agonistas Receptor de Péptidos Similares al GlucagónAsunto(s)
Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Hipoglucemiantes , Fragmentos Fc de Inmunoglobulinas , Obesidad , Diálisis Peritoneal , Proteínas Recombinantes de Fusión , Humanos , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/análogos & derivados , Proteínas Recombinantes de Fusión/uso terapéutico , Obesidad/complicaciones , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Hipoglucemiantes/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicacionesAsunto(s)
Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Hipoglucemiantes , Fragmentos Fc de Inmunoglobulinas , Obesidad , Diálisis Peritoneal , Proteínas Recombinantes de Fusión , Humanos , Péptidos Similares al Glucagón/análogos & derivados , Péptidos Similares al Glucagón/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Obesidad/complicaciones , Hipoglucemiantes/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Femenino , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/terapiaRESUMEN
Background and Objectives: The rise in global diabetes cases, reaching a staggering 529 million in 2021 from 108 million in 1980, underscores the urgency of addressing its complications, notably macrovascular ones like coronary artery, cerebrovascular, and peripheral artery diseases, which contribute to over 50% of diabetes mortality. Atherosclerosis, linked to hyperglycemia-induced endothelial dysfunction, is pivotal in cardiovascular disease development. Cytokines, including pentraxin 3 (PTX3), copeptin, lipoprotein(a) [Lp(a)], and matrix metalloproteinase-9 (MMP-9), influence atherosclerosis progression and plaque vulnerability. Inhibiting atherosclerosis progression is crucial, especially in diabetic individuals. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), increasingly used for type 2 diabetes, show promise in reducing the cardiovascular risk, sparking interest in their effects on atherogenesis. This study sought to examine the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on biomarkers that indicate the instability of atherosclerotic plaques. These biomarkers include pentraxin 3 (PTX3), copeptin (CPC), matrix metalloproteinase-9 (MMP-9), and lipoprotein(a) [Lp(a)]. Materials and Methods: A total of 34 participants, ranging in age from 41 to 81 years (with an average age of 61), who had been diagnosed with type 2 diabetes mellitus (with a median HbA1c level of 8.8%), dyslipidemia, and verified atherosclerosis using B-mode ultrasonography, were included in the study. All subjects were eligible to initiate treatment with a GLP-1 RA-dulaglutide. Results: Significant reductions in anthropometric parameters, blood pressure, fasting glucose levels, and HbA1c levels were observed posttreatment. Moreover, a notable decrease in biochemical markers associated with atherosclerotic plaque instability, particularly PTX3 and MMP-9 (p < 0.001), as well as Lp(a) (p < 0.05), was evident following the GLP-1 RA intervention. Conclusions: These findings underscore the potential of GLP-1 RAs in mitigating atherosclerosis progression and plaque vulnerability, thus enhancing cardiovascular outcomes in individuals with type 2 diabetes mellitus.
Asunto(s)
Biomarcadores , Proteína C-Reactiva , Citocinas , Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Hipoglucemiantes , Metaloproteinasa 9 de la Matriz , Placa Aterosclerótica , Proteínas Recombinantes de Fusión , Componente Amiloide P Sérico , Humanos , Proyectos Piloto , Biomarcadores/sangre , Persona de Mediana Edad , Masculino , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Femenino , Placa Aterosclerótica/sangre , Placa Aterosclerótica/tratamiento farmacológico , Proteína C-Reactiva/análisis , Componente Amiloide P Sérico/análisis , Péptidos Similares al Glucagón/análogos & derivados , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/farmacología , Metaloproteinasa 9 de la Matriz/sangre , Anciano , Citocinas/sangre , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Proteínas Recombinantes de Fusión/uso terapéutico , Aterosclerosis/sangre , Aterosclerosis/tratamiento farmacológico , Lipoproteína(a)/sangre , Glicopéptidos , Fragmentos Fc de InmunoglobulinasRESUMEN
Initially developed as medications for diabetes mellitus, GLP-1 agonists have gained much popularity in the treatment of obesity and weight loss. The present case describes a 69-year-old woman with a history of peptic ulcer and use of NSAIDs, who presented with abdominal pain and oral intolerance refractory to conventional management, for which an upper digestive endoscopy was performed, diagnosing severe gastroparesis. Asking more about the story, revealed surreptitious use of semaglutide. She continued with supportive therapy and the symptoms resolved spontaneously. The present case report aims to warn of the potential risks of the use of GLP-1 analogues in the context of endoscopy with sedation.
Asunto(s)
Gastroparesia , Agonistas Receptor de Péptidos Similares al Glucagón , Pérdida de Peso , Anciano , Femenino , Humanos , Gastroparesia/inducido químicamente , Agonistas Receptor de Péptidos Similares al Glucagón/administración & dosificación , Agonistas Receptor de Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/análogos & derivados , Péptidos Similares al Glucagón/efectos adversos , Índice de Severidad de la Enfermedad , Pérdida de Peso/efectos de los fármacosRESUMEN
Type 2 diabetes mellitus (T2DM) significantly impairs the functionality and number of endothelial progenitor cells (EPCs) and resident endothelial cells, critical for vascular repair and regeneration, exacerbating the risk of vascular complications. GLP-1 receptor agonists, like dulaglutide, have emerged as promising therapeutic agents due to their multifaceted effects, including the enhancement of EPC activity and protection of endothelial cells. This study investigates dulaglutide's effects on peripheral blood levels of CD34+ and CD133+ cells in a mouse model of lower limb ischemia and its protective mechanisms against high-glucose-induced damage in endothelial cells. Results demonstrated that dulaglutide significantly improves blood flow, reduces tissue damage and inflammation in ischemic limbs, and enhances glycemic control. Furthermore, dulaglutide alleviated high-glucose-induced endothelial cell damage, evident from improved tube formation, reduced reactive oxygen species accumulation, and restored endothelial junction integrity. Mechanistically, dulaglutide mitigated mitochondrial fission in endothelial cells under high-glucose conditions, partly through maintaining SIRT1 expression, which is crucial for mitochondrial dynamics. This study reveals the potential of dulaglutide as a therapeutic option for vascular complications in T2DM patients, highlighting its role in improving endothelial function and mitochondrial integrity.
Asunto(s)
Diabetes Mellitus Experimental , Células Progenitoras Endoteliales , Péptidos Similares al Glucagón , Glucosa , Fragmentos Fc de Inmunoglobulinas , Dinámicas Mitocondriales , Proteínas Recombinantes de Fusión , Sirtuina 1 , Animales , Ratones , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Células Progenitoras Endoteliales/efectos de los fármacos , Células Progenitoras Endoteliales/metabolismo , Péptidos Similares al Glucagón/análogos & derivados , Péptidos Similares al Glucagón/farmacología , Péptidos Similares al Glucagón/uso terapéutico , Glucosa/metabolismo , Hipoglucemiantes/farmacología , Fragmentos Fc de Inmunoglobulinas/farmacología , Isquemia/metabolismo , Isquemia/tratamiento farmacológico , Isquemia/patología , Ratones Endogámicos C57BL , Dinámicas Mitocondriales/efectos de los fármacos , Proteínas Recombinantes de Fusión/farmacología , Sirtuina 1/efectos de los fármacos , Sirtuina 1/metabolismoRESUMEN
OBJECTIVE: This prospective study aimed to describe the clinical course in terms of glycemic outcomes, body weight, and adverse events during the first 12 weeks following a switch from glucagon-like peptide-1 receptor agonists (GLP-1 RAs) directly to tirzepatide 5 mg. METHODS: Participants were ≥18 years with type 2 diabetes (T2D), glycated hemoglobin (HbA1c) ≥6.5% to ≤9.0%, body mass index ≥25 kg/m2 and were on a stable treatment dose of GLP-1 RAs (liraglutide every day [1.2, 1.8 mg], semaglutide once-weekly [0.5, 1.0, 2.0 mg], or dulaglutide once-weekly [0.75, 1.5, 3.0, and 4.5 mg]) for ≥3 months at baseline. The primary end point was HbA1c change from baseline at week 12. Secondary end points included change from baseline in fasting serum glucose, body weight, and glucose assessed by continuous glucose monitoring. Safety was also assessed. RESULTS: Participants were 58.3 years on average, with baseline HbA1c 7.39%, body mass index 35.18 kg/m2, T2D duration around 12.4 years, and included 55% females. Semaglutide (55%) and dulaglutide (42%) were the most commonly used GLP-1 RAs at baseline with semaglutide 1.0 mg and dulaglutide 1.5 mg being the most common treatment doses. At week 12, mean HbA1c changed from baseline by -0.43%, fasting serum glucose by -7.83 mg/dL, and body weight by -2.15 kg (all P < .01). Glycemic outcomes and body weight improved in participants in all baseline GLP-1 RA subgroups. Twenty participants (13.2%) developed gastrointestinal events. Three (2%) participants discontinued tirzepatide due to adverse events. There were no severe hypoglycemic events or deaths. CONCLUSION: In this prospective study, when people with T2D on stable GLP-1 RA treatment were switched directly to tirzepatide 5 mg, they experienced improved glycemic outcomes and additional weight reduction with an acceptable risk of adverse gastrointestinal events over 12 weeks.
Asunto(s)
Glucemia , Diabetes Mellitus Tipo 2 , Agonistas Receptor de Péptidos Similares al Glucagón , Péptidos Similares al Glucagón , Hipoglucemiantes , Fragmentos Fc de Inmunoglobulinas , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Glucemia/efectos de los fármacos , Glucemia/análisis , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Sustitución de Medicamentos , Polipéptido Inhibidor Gástrico , Agonistas Receptor de Péptidos Similares al Glucagón/administración & dosificación , Agonistas Receptor de Péptidos Similares al Glucagón/efectos adversos , Receptor del Péptido 2 Similar al Glucagón , Péptidos Similares al Glucagón/análogos & derivados , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Hemoglobina Glucada/análisis , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Fragmentos Fc de Inmunoglobulinas/administración & dosificación , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Fragmentos Fc de Inmunoglobulinas/efectos adversos , Liraglutida/administración & dosificación , Liraglutida/uso terapéutico , Liraglutida/efectos adversos , Estudios Prospectivos , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/uso terapéutico , Proteínas Recombinantes de Fusión/efectos adversosRESUMEN
AIM: To assess the efficacy and safety of dulaglutide 1.5 mg versus dulaglutide 0.75 mg in Japanese participants with type 2 diabetes (T2D). MATERIALS AND METHODS: A Phase 3, multicentre, randomized, double-blind, parallel-group study was conducted in Japanese participants aged ≥20 years, with T2D for ≥6 months and inadequate glycaemic control, while on a single oral antihyperglycaemic medication (NCT04809220). The primary objective was to evaluate superiority of dulaglutide 1.5 mg versus dulaglutide 0.75 mg measured by mean change in glycated haemoglobin (HbA1c) from baseline to 26 weeks. Other efficacy and safety endpoints were evaluated at 26 and 52 weeks. All statistical analyses were conducted using the intention-to-treat population. RESULTS: Overall, 591 participants were randomized to once-weekly dulaglutide 1.5 mg or 0.75 mg. At Week 26, dulaglutide 1.5 mg was superior to dulaglutide 0.75 mg in HbA1c reduction from baseline (least squares mean [LSM] difference -0.29% [95% confidence interval {CI} -0.43, -0.14]). At Week 52, the dulaglutide 1.5-mg arm had a significantly greater proportion of participants who achieved HbA1c <7.0% (46.3% vs. 38.5%; p = 0.03) and showed significantly greater reduction in fasting serum glucose (LSM difference -9.4 mg/dL [95% CI -14.4, -4.3]; p < 0.001) versus the dulaglutide 0.75-mg arm. No statistically significant change in body weight was observed in either treatment arm. Overall, 442 participants (75.4%) experienced treatment emergent adverse events (TEAEs). Constipation (11.3%), diarrhoea (9.6%) and pyrexia (9.0%) were the most commonly reported TEAEs. CONCLUSIONS: Dulaglutide 1.5 mg once weekly demonstrated superior glycaemic control versus dulaglutide 0.75 mg once weekly, with comparable safety and tolerability, in Japanese people with T2D.
Asunto(s)
Glucemia , Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Hemoglobina Glucada , Hipoglucemiantes , Fragmentos Fc de Inmunoglobulinas , Proteínas Recombinantes de Fusión , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversos , Proteínas Recombinantes de Fusión/uso terapéutico , Fragmentos Fc de Inmunoglobulinas/efectos adversos , Fragmentos Fc de Inmunoglobulinas/administración & dosificación , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Péptidos Similares al Glucagón/análogos & derivados , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/efectos adversos , Péptidos Similares al Glucagón/uso terapéutico , Masculino , Persona de Mediana Edad , Femenino , Método Doble Ciego , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Hemoglobina Glucada/metabolismo , Hemoglobina Glucada/análisis , Japón , Anciano , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Resultado del Tratamiento , Adulto , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Esquema de Medicación , Pueblos del Este de AsiaRESUMEN
INTRODUCTION: Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have changed the landscape of type 2 diabetes (T2D) management due to their cardio-renal benefits, their glucose-lowering efficacy and weight loss (WL) maintenance. However, the response to GLP-1 RA monotherapy is heterogeneous. Additionally, the majority of GLP-1 RAs are injectable treatments. Oral GLP-1 RAs and injectable combinations of GLP-1 with other entero-pancreatic hormones (glucose-dependent insulinotropic polypeptide (GIP), glucagon and amylin) are under development for T2D and obesity management. AREAS COVERED: Herein, we review the data on (i) oral GLP-1 RAs (oral semaglutide 25/50 mg and orforglipron) and (ii) dual/triple agonists (tirzepatide, cagrilintide 2.4 mg/semaglutide 2.4 mg, survodutide, mazdutide, retatrutide) that have recently completed phase 3 trials for T2D or are currently in phase 3 clinical trials. Tirzepatide is the first approved dual agonist (GLP-1/GIP) for T2D and obesity management. EXPERT OPINION: We are in a new era in T2D management where entero-pancreatic hormone-based treatments can result in ≥15% WL and euglycemia for many people with T2D. Multiple molecules with different mechanisms of action are under development for T2D, obesity and other metabolic complications. Data on their cardio-renal benefits, long-term efficacy and safety as well as their cost-effectiveness will better inform their position in treatment algorithms.
Asunto(s)
Diabetes Mellitus Tipo 2 , Receptor del Péptido 1 Similar al Glucagón , Hipoglucemiantes , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Adulto , Administración Oral , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/farmacología , Péptidos Similares al Glucagón/análogos & derivados , Animales , Obesidad/tratamiento farmacológico , Quimioterapia Combinada , Agonistas Receptor de Péptidos Similares al GlucagónRESUMEN
BACKGROUND: Antipsychotics are indispensable in the treatment of severe mental illneses, however adverse metabolic effects including diabetes, weight gain, dyslipidemia, and related cardiovascular morbidity are common, and current pharmacological strategies for their management are unsatisfactory. Glucagon-like 1 peptide receptor agonists (GLP-1 RAs) are approved for the treatment of type 2 diabetes and obesity hold promise for the management of antipsychotic-associated adverse metabolic effects. METHODS: To characterize the molecular effects and identify biomarkers for GLP-1 RA preventive treatment, Sprague-Dawley female rats were treated with long-acting formulations of the antipsychotic olanzapine and the GLP-1 RA dulaglutide for 8 days. A pair-feeding protocol evaluated the combined effects of dulaglutide and food restriction on an olanzapine-induced metabolic phenotype. Body weight and food consumption were recorded. Biochemical analysis included a lipid profile, a spectrum of gastrointestinal and adipose tissue-derived hormones, and fibroblast growth factor 21 serum levels. RESULTS: Olanzapine induced hyperphagia, weight gain, increased serum triglycerides and HDL cholesterol. Food restriction affected the OLA-induced phenotype but not serum markers. Dulaglutide led to a modest decrease in food intake, with no effect on weight gain, and did not reverse the OLA-induced changes in serum lipid parameters. Concomitant dulaglutide and food restriction resulted in weight loss, decreased feed efficiency, and lower total and HDL cholesterol. CONCLUSIONS: A combined strategy of dulaglutide and food restriction manifested a massive synergistic benefit. GLP-1RAs represent a promising strategy and deserve thorough future research. Our findings underline the potential importance of lifestyle intervention in addition to GLP-1 RA treatment.
Asunto(s)
Péptidos Similares al Glucagón , Fragmentos Fc de Inmunoglobulinas , Olanzapina , Ratas Sprague-Dawley , Proteínas Recombinantes de Fusión , Animales , Fragmentos Fc de Inmunoglobulinas/farmacología , Péptidos Similares al Glucagón/análogos & derivados , Péptidos Similares al Glucagón/farmacología , Olanzapina/farmacología , Olanzapina/efectos adversos , Femenino , Proteínas Recombinantes de Fusión/farmacología , Ratas , Antipsicóticos/farmacología , Antipsicóticos/efectos adversos , Ingestión de Alimentos/efectos de los fármacos , Receptor del Péptido 1 Similar al Glucagón/agonistas , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Aumento de Peso/efectos de los fármacos , Modelos Animales de Enfermedad , Benzodiazepinas/farmacología , Benzodiazepinas/efectos adversos , Peso Corporal/efectos de los fármacos , Restricción Calórica/métodosRESUMEN
PURPOSE: Glucagon-like receptor agonists (GLP1-RAs) have raised peri-procedural concerns due to their potential to delay gastric emptying. The American Association of Anesthesiologists has advised pausing a single dose before elective endoscopy. However, a subsequent directive from multiple gastroenterology societies underscored the need for further assessment to substantiate this practice. We aimed to evaluate the frequency of serious adverse events and retained gastric products during endoscopic sleeve gastroplasty (ESG) with uninterrupted GLP1-RA use. MATERIALS AND METHODS: We conducted a retrospective evaluation of all patients undergoing ESG while on GLP1-RAs at three centers from August 2022 to February 2024. Per standard protocol, all patients had refrained from solid foods for at least 24 h and maintained nil per os for 12 h preceding their ESG. Records were reviewed for patient characteristics and medication type and doses. Primary outcomes included serious adverse events and retained gastric products based on patient records, procedure reports, and procedural videos. RESULTS: Fifty-seven consecutive adults (89.5% women, mean age of 44 ± 9 years, mean BMI of 40.1 ± 8.1 kg/m2, 35.1% with T2DM, and 26.3% with pre-T2DM) underwent ESG without stopping GLP1-RAs, which included semaglutide (45.6%), liraglutide (19.3%), dulaglutide (22.8%), and tirzepatide (12.3%). During intubation, endoscopy, and recovery, there were no instances of retained gastric solids, pulmonary aspiration, gastroesophageal regurgitation, or hypoxia. CONCLUSION: A ≥ 24-h pre-endoscopy liquid-only diet with ≥ 12-h pre-endoscopy fast may negate the need for GLP1-RA interruption for routine upper endoscopy in adults with native gastric anatomy.
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Gastroplastia , Receptor del Péptido 1 Similar al Glucagón , Péptidos Similares al Glucagón , Humanos , Femenino , Masculino , Estudios Retrospectivos , Adulto , Gastroplastia/métodos , Receptor del Péptido 1 Similar al Glucagón/agonistas , Persona de Mediana Edad , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/análogos & derivados , Obesidad Mórbida/cirugía , Vaciamiento Gástrico/efectos de los fármacos , Hipoglucemiantes/uso terapéutico , Liraglutida/uso terapéutico , Fragmentos Fc de Inmunoglobulinas , Proteínas Recombinantes de FusiónRESUMEN
The use of dulaglutide, a common medication for managing type 2 diabetes, rarely causes elevated pancreatic tumour markers. Here, we report the case of a woman in her mid-60s with diabetes for over 10 years. The patient presented with markedly elevated serum CA19-9 and CA242 levels revealed during a routine health examination despite being asymptomatic. She had been receiving dulaglutide injections for 16 months. Imaging and interventional assessments did not reveal any hepatobiliary, gastrointestinal or pancreatic neoplasm. After excluding alternate diagnoses, the patient was determined to exhibit an adverse reaction to dulaglutide use. Management involved the discontinuation of dulaglutide, which resulted in normalisation of serum CA19-9 and CA242 levels within 6 weeks. This case underscores the importance of discontinuing dulaglutide and monitoring changes in the biomarker levels in asymptomatic patients receiving dulaglutide, rather than immediately resorting to imaging and endoscopic examinations.
Asunto(s)
Antígeno CA-19-9 , Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Hipoglucemiantes , Fragmentos Fc de Inmunoglobulinas , Proteínas Recombinantes de Fusión , Humanos , Proteínas Recombinantes de Fusión/efectos adversos , Proteínas Recombinantes de Fusión/uso terapéutico , Proteínas Recombinantes de Fusión/administración & dosificación , Péptidos Similares al Glucagón/análogos & derivados , Péptidos Similares al Glucagón/efectos adversos , Péptidos Similares al Glucagón/uso terapéutico , Femenino , Fragmentos Fc de Inmunoglobulinas/efectos adversos , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Antígeno CA-19-9/sangre , Persona de Mediana Edad , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/sangreRESUMEN
Inflammation plays a pathophysiological role in atherosclerosis and its clinical consequences. In addition to glycemic control, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are of wide concern for cardioprotective effects. The structure, half-life, homology, and clinical efficacy of GLP-1RAs exhibit remarkable disparity. Several studies have compared the disparities in anti-inflammatory effects between daily and weekly GLP-1RAs. This study aimed to compare the similarities and differences between liraglutide and dulaglutide in terms of inhibiting atherosclerotic inflammation and improving co-cultured endothelial cell function. The expression of inflammation markers was examined by immunofluorescence, Western blotting, and real-time PCR. The tube-forming ability of endothelial cells was tested on Matrigel. The results verify that 10/50/100 nmol/L liraglutide and 100 nmol/L dulaglutide markedly suppressed the expression of inflammatory factors in LPS-induced atherosclerosis after 24 and 72 hours, respectively. Moreover, they promoted the polarization of M1 macrophages toward the M2 phenotype and improved the function of co-cultured endothelial cells. Both liraglutide and dulaglutide ameliorate atherosclerosis development. The difference between the two resided in the extended intervention duration required to observe the effect of dulaglutide, and liraglutide demonstrated a superior dose-dependent manner. We provide a potential strategy to understand the dynamics of drug action and possible timing administration.