RESUMEN
Previously, no randomized controlled trials investigated the renoprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1RA) as the primary endpoint in patients with diabetes and chronic kidney disease. In the FLOW trial, Perkovic et al. showed that once-weekly semaglutide reduced kidney failure, kidney-related death, and cardiovascular death by 24% as compared with placebo in patients with type 2 diabetes at high risk of renal progression.1.
Asunto(s)
Diabetes Mellitus Tipo 2 , Receptor del Péptido 1 Similar al Glucagón , Péptidos Similares al Glucagón , Insuficiencia Renal Crónica , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Insuficiencia Renal Crónica/tratamiento farmacológico , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/farmacología , Péptidos Similares al Glucagón/administración & dosificación , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Nefropatías Diabéticas/tratamiento farmacológicoRESUMEN
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 impacts mental health greatly. Psychological factors may influence the effectiveness of its treatment. This study aimed to compare symptoms of generalised anxiety disorder and depression among adult women across different weight categories. The study sample comprised 1105 adult women. The computer-assisted web interview (CAWI) utilising the seven-item Generalised Anxiety Disorders Scale (GAD-7) and the nine-item Patient Health Questionnaire (PHQ-9) was used. Both GAD-7 and PHQ-9 scores correlated positively with BMI (r = 0.121, p < 0.001 and r = 0.173, p < 0.001, respectively) and negatively with age (r = -0.106, p < 0.001 and r = -0.103, p < 0.001, respectively). Patients undergoing treatment with semaglutide scored lower for both anxiety symptoms (8.71 ± 6.16, p = 0.013) and depression symptoms (9.76 ± 6.37, p = 0.013). Women who underwent bariatric surgery screened less frequently for anxiety (8.03 ± 6.27, p = 0.002) but not for depression. An interdisciplinary approach involving mental health professionals within the therapeutic team can comprehensively address factors contributing to obesity development and treatment outcomes. Further investigation of semaglutide's use is needed due to the promising evidence suggesting a positive effect on decreasing the severity of depression and anxiety symptoms to assess the direct or indirect character of this influence.
Asunto(s)
Trastornos de Ansiedad , Depresión , Obesidad , Humanos , Femenino , Adulto , Obesidad/psicología , Obesidad/tratamiento farmacológico , Persona de Mediana Edad , Trastornos de Ansiedad/tratamiento farmacológico , Depresión/tratamiento farmacológico , Polonia , Fármacos Antiobesidad/uso terapéutico , Péptidos Similares al Glucagón/uso terapéutico , Ansiedad/tratamiento farmacológico , Cuestionario de Salud del Paciente , Adulto Joven , Cirugía Bariátrica , Índice de Masa Corporal , Encuestas y CuestionariosRESUMEN
Although, in randomized clinical trials, once-weekly subcutaneous semaglutide (OW s.c.) has demonstrated superior efficacy in comparison with placebo and active controls in terms of glycemic control and body weight reduction in patients with type 2 diabetes mellitus (T2DM), these results need to be confirmed in a real-world (RW) setting. An RW ambispective study (6 months retrospective and 6 months prospective) was conducted in 10 tertiary hospitals in Spain. We evaluated changes in HbA1c and body weight in patients with T2DM treated with semaglutide OW s.c. Additionally, we analyzed different subgroups of patients treated with semaglutide OW s.c. as an add-on to glucose-lowering therapy. A total of 752 patients with a mean age of 60.2 years, a mean HbA1c level of 8.5%, a mean body weight of 101.6 kg, and a mean T2DM duration of 10 years were included. At 12 months, compared with baseline, there was a mean difference of -2.1% in HbA1c levels (p < 0.001) and a mean difference of 9.2 kg in body weight (p < 0.001). Moreover, there were statistically significant differences (p < 0.001) between baseline and month 12 in both HbA1c and body weight in the four subgroups receiving semaglutide OW s.c. as an add-on to glucose-lowering therapy. Semaglutide OW s.c. was well tolerated, with gastrointestinal disorders being the most commonly reported side effects. In this RW study, 12 months of treatment with semaglutide OW s.c. in patients with T2DM was associated with significant and clinically relevant improvements in glycemic control and weight loss, regardless of the glucose-lowering therapy received, and the overall safety profile was positive.
Asunto(s)
Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Hemoglobina Glucada , Hipoglucemiantes , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Masculino , Femenino , Persona de Mediana Edad , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/efectos adversos , España , Hemoglobina Glucada/análisis , Hipoglucemiantes/administración & dosificación , Anciano , Inyecciones Subcutáneas , Estudios Prospectivos , Glucemia/efectos de los fármacos , Estudios Retrospectivos , Pérdida de Peso/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Resultado del Tratamiento , Esquema de Medicación , Control Glucémico/métodosRESUMEN
The STEP-HFpEF DM trial1 showed that semaglutide improved body weight, systemic inflammation, and heart failure symptoms in people with obesity-related heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes. By addressing both metabolic and cardiovascular risk, semaglutide is a promising therapeutic option for HFpEF in addition to SGLT2i.
Asunto(s)
Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Insuficiencia Cardíaca , Obesidad , Volumen Sistólico , Humanos , Obesidad/tratamiento farmacológico , Obesidad/fisiopatología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Volumen Sistólico/efectos de los fármacos , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacologíaRESUMEN
This cross-sectional study examines trends in US prescription fills for semaglutide products by payment method between January 2021 and December 2023.
Asunto(s)
Péptidos Similares al Glucagón , Hipoglucemiantes , Humanos , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/economía , Hipoglucemiantes/economía , Hipoglucemiantes/uso terapéutico , Estados Unidos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/economíaRESUMEN
This qualitative study assesses the quality, amount of active ingredient, and characteristics associated with counterfeiting of semaglutide purchased from illegal online pharmacies without a prescription.
Asunto(s)
Péptidos Similares al Glucagón , Humanos , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Femenino , Masculino , Medición de Riesgo , Persona de Mediana Edad , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Adulto , Diabetes Mellitus Tipo 2/tratamiento farmacológico , AncianoRESUMEN
Melanocortin 4 receptor (MC4R) mutations are the commonest cause of monogenic obesity through dysregulation of neuronal pathways in the hypothalamus and prefrontal cortex that regulate hunger and satiety. MC4R also regulates neuropathic pain pathways via JNK signaling after nerve injury. We show evidence of corneal small fiber degeneration in 2 siblings carrying a heterozygous missense variant c.508A>G, p.Ille170Val in the MC4R gene. Both children were treated with once weekly semaglutide for 6 months with no change in weight, and only a minor improvement in HbA1c and lipid profile. However, there was evidence of nerve regeneration with an increase in corneal nerve fiber density (CNFD) [child A (13.9%), child B (14.7%)], corneal nerve branch density (CNBD) [child A (110.2%), child B (58.7%)] and corneal nerve fiber length (CNFL) [child A (21.5%), child B (44.0%)].
Asunto(s)
Regeneración Nerviosa , Receptor de Melanocortina Tipo 4 , Humanos , Receptor de Melanocortina Tipo 4/genética , Masculino , Femenino , Niño , Regeneración Nerviosa/efectos de los fármacos , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/farmacología , Fibras Nerviosas/efectos de los fármacos , Fibras Nerviosas/patología , Mutación , Obesidad/tratamiento farmacológico , Obesidad/genética , Córnea/efectos de los fármacos , Córnea/inervación , Córnea/patología , Obesidad Infantil/tratamiento farmacológico , AdolescenteRESUMEN
BACKGROUND & AIMS: Very-low calorie diets (VLCD) and the glucagon-like peptide-1 receptor agonist (GLP1RA) Semaglutide induce significant weight loss and improve glycaemic control in individuals with type 2 diabetes (T2D). This pilot study was conducted to explore the comparative short-term effects of these interventions individually, and in combination, on weight, body composition and metabolic outcomes. METHODS: Thirty individuals with T2D (age 18-75 years, BMI 27-50 kg m-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks. Measurement of weight and glycated haemoglobin (HbA1c), dual energy X-ray absorptiometry, and intravenous glucose tolerance tests (IVGTT) were performed at baseline and post-intervention. Diet diaries were utilised to assess compliance. Insulin first phase response during IVGTT provided a marker of pancreatic beta-cell function, and insulin sensitivity was estimated using HOMA-IR. RESULTS: Significantly greater reductions in body weight and fat mass were observed in VLCD and COMB, than SEM (p < 0.01 v both). VLCD and COMB resulted in a 5.4 and 7 percentage-point greater weight loss than SEM, respectively. HbA1c and fasting glucose reduced significantly in all groups, however fasting insulin and HOMA-IR improved in VLCD and COMB only. Insulin first phase response during IVGTT increased in SEM and COMB, and this increase was significantly greater in COMB than VLCD (p < 0.01). CONCLUSION: VLCD elicited greater short-term losses of weight and fat mass than Semaglutide. Adding VLCD to Semaglutide stimulated further weight loss than Semaglutide alone. The combination did not yield any additive effects on weight and body composition above VLCD alone, but did provoke greater improvements in pancreatic beta-cell function. Thus, combination of Semaglutide and VLCD warrants further exploration as a novel approach to T2D management.
Asunto(s)
Glucemia , Restricción Calórica , Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Hemoglobina Glucada , Hipoglucemiantes , Pérdida de Peso , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/dietoterapia , Persona de Mediana Edad , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/farmacología , Masculino , Femenino , Adulto , Anciano , Restricción Calórica/métodos , Proyectos Piloto , Pérdida de Peso/efectos de los fármacos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacología , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Adolescente , Adulto Joven , Composición Corporal/efectos de los fármacos , Insulina/sangre , Resistencia a la Insulina , Prueba de Tolerancia a la Glucosa , Terapia CombinadaAsunto(s)
Péptidos Similares al Glucagón , Humanos , Péptidos Similares al Glucagón/efectos adversos , Péptidos Similares al Glucagón/uso terapéutico , Síndrome de Lipodistrofia Asociada a VIH/inducido químicamente , Síndrome de Lipodistrofia Asociada a VIH/tratamiento farmacológico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéuticoAsunto(s)
Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Insuficiencia Cardíaca , Hipoglucemiantes , Obesidad , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Insuficiencia Cardíaca/etiología , Obesidad/complicaciones , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéuticoAsunto(s)
Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Insuficiencia Cardíaca , Hipoglucemiantes , Obesidad , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Insuficiencia Cardíaca/etiología , Obesidad/complicaciones , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéuticoAsunto(s)
Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Insuficiencia Cardíaca , Hipoglucemiantes , Obesidad , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Insuficiencia Cardíaca/etiología , Obesidad/complicaciones , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéuticoRESUMEN
BACKGROUND: Oral semaglutide in older subjects with type 2 diabetes was as effective as in younger subjects, according to phase 3 clinical trials. However, its efficacy can be limited in very aged population, due to the presence of impaired cognitive function and the complex instructions for its use. Here, we investigated its efficacy and safety by further age bracket in older subjects in real-world. METHODS: We retrospectively studied subjects > 65 years of age with type 2 diabetes who started oral semaglutide treatment. The primary outcome was the change in glycated hemoglobin (HbA1c) over 6 months. Adverse events and cognitive function were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) and the Hasegawa Dementia Rating Scale-revised (HDS-R). The achievement rate of glycemic targets was evaluated based on the age, health status of subjects and their use of anti-diabetic agents which can cause hypoglycemia, with additional analysis between two subgroups; early (65-74) versus late (≥ 75) older. Furthermore, we evaluated the relationships between their improvements in HbA1c and the baseline characteristics of the subjects, including their cognitive function and insulin secretory capacity. RESULTS: We studied the efficacy of the drug in 24 subjects. Their HbA1c and body weight significantly decreased (- 13.1 ± 7.5 mmol/mol and - 3.0 ± 2.4 kg, respectively; P < 0.01). Although cognitive function was lower in the late older group (r = -0.57, P < 0.01), changes in HbA1c showed no difference between the two subgroups (P = 0.66) and it correlated with the insulin secretory capacity rather than cognitive function (r = -0.49, P < 0.05). Glycemic targets were more likely to be achieved (P < 0.01), but HbA1c excessively decreased in late older subjects who were also using insulin or an insulin secretagogue. The frequency of adverse events was similar to that in the clinical trial, whereas discontinuation of medication were more frequent among the late older subjects (Early; n = 2, Late; n = 4). CONCLUSIONS: Oral semaglutide improves the glycemic control of older subjects, but it might be a risk for potential hypoglycemia and discontinuation because of adverse events in subjects of ≥ 75 years. Attention should be paid to insulin secretory capacity and concomitant medications rather than concern about adherence.
Asunto(s)
Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Hemoglobina Glucada , Hipoglucemiantes , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Masculino , Femenino , Estudios Retrospectivos , Anciano , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Hemoglobina Glucada/análisis , Anciano de 80 o más Años , Administración Oral , Glucemia/análisis , Glucemia/efectos de los fármacos , Resultado del Tratamiento , Hipoglucemia/inducido químicamente , Estudios de Seguimiento , Cognición/efectos de los fármacosAsunto(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
Obesity is associated with an increased risk of incident heart failure with preserved ejection fraction (HFpEF) and, among patients with existing heart failure, is associated with worse quality of life, higher symptom burden, and more HF hospitalizations. Anti-obesity medication (AOM) semaglutide has been shown to be efficacious at both causing intentional weight loss and improving HF symptom burden, with some evidence to suggest that HF clinical events may also be reduced. Additional ongoing trials of AOM in patients with cardiovascular disease, including HFpEF, will further improve insight into the potential role of managing obesity to improve HF status among patients with HFpEF and obesity.
Asunto(s)
Fármacos Antiobesidad , Insuficiencia Cardíaca , Obesidad , Volumen Sistólico , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/complicaciones , Volumen Sistólico/fisiología , Volumen Sistólico/efectos de los fármacos , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Obesidad/fisiopatología , Fármacos Antiobesidad/uso terapéutico , Calidad de Vida , Pérdida de Peso/efectos de los fármacos , Péptidos Similares al GlucagónRESUMEN
Newly conducted research suggests that metabolic disorders, like diabetes and obesity, play a significant role as risk factors for psychiatric disorders. This connection presents a potential avenue for creating novel antidepressant medications by repurposing drugs originally developed to address antidiabetic conditions. Earlier investigations have shown that GLP-1 (Glucagon-like Peptide-1) analogs exhibit neuroprotective qualities in various models of neurological diseases, encompassing conditions such as Alzheimer's disease, Parkinson's disease, and stroke. Moreover, GLP-1 analogs have demonstrated the capability to enhance neurogenesis, a process recognized for its significance in memory formation and the cognitive and emotional aspects of information processing. Nonetheless, whether semaglutide holds efficacy as both an antidepressant and anxiolytic agent remains uncertain. To address this, our study focused on a mouse model of depression linked to type 2 diabetes induced by a High Fat Diet (HFD). In this model, we administered semaglutide (0.05 mg/Kg intraperitoneally) on a weekly basis to evaluate its potential as a therapeutic option for depression and anxiety. Diabetic mice had higher blood glucose, lipidic profile, and insulin resistance. Moreover, mice fed HFD showed higher serum interleukin (IL)-1ß and lipopolysaccharide (LPS) associated with impaired humor and cognition. The analysis of behavioral responses revealed that the administration of semaglutide effectively mitigated depressive- and anxiety-like behaviors, concurrently demonstrating an enhancement in cognitive function. Additionally, semaglutide treatment protected synaptic plasticity and reversed the hippocampal neuroinflammation induced by HFD fed, improving activation of the insulin pathway, demonstrating the protective effects of semaglutide. We also found that semaglutide treatment decreased astrogliosis and microgliosis in the dentate gyrus region of the hippocampus. In addition, semaglutide prevented the DM2-induced impairments of pro-opiomelanocortin (POMC), and G-protein-coupled receptor 43 (GPR43) and simultaneously increased the NeuN + and Glucagon-like Peptide-1 receptor (GLP-1R+) neurons in the hippocampus. Our data also showed that semaglutide increased the serotonin (5-HT) and serotonin transporter (5-HTT) and glutamatergic receptors in the hippocampus. At last, semaglutide changed the gut microbiota profile (increasing Bacterioidetes, Bacteroides acidifaciens, and Blautia coccoides) and decreased leaky gut, improving the gut-brain axis. Taken together, semaglutide has the potential to act as a therapeutic tool for depression and anxiety.