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Trastorno por Atracón , Diabetes Mellitus Tipo 1 , Péptidos Similares al Glucagón , Obesidad , Humanos , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/complicaciones , Obesidad/tratamiento farmacológico , Obesidad/complicaciones , Trastorno por Atracón/tratamiento farmacológico , Femenino , Hipoglucemiantes/uso terapéutico , Adulto , Resultado del Tratamiento , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Heart failure with mildly reduced or preserved ejection fraction (hereafter referred to as HFpEF) is the most common type of heart failure and is associated with a high risk of hospitalisation and death, especially in patients with overweight, obesity, or type 2 diabetes. In the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide improved heart failure-related symptoms and physical limitations in participants with HFpEF. Whether semaglutide also reduces clinical heart failure events in this group remains to be established. METHODS: We conducted a post-hoc pooled, participant-level analysis of four randomised, placebo-controlled trials (SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM) to examine the effects of once-weekly subcutaneous semaglutide (2·4 mg in SELECT, STEP-HFpEF, and STEP-HFpEF DM; 1·0 mg in FLOW) on heart failure events. The STEP-HFpEF and STEP-HFpF DM trials enrolled participants with obesity-related HFpEF, the SELECT trial enrolled participants with atherosclerotic cardiovascular disease and overweight or obesity, and the FLOW trial enrolled participants with type 2 diabetes and chronic kidney disease. Hence, for this analysis, we include all participants from the STEP-HFpEF trials and those with an investigator-reported history of HFpEF from SELECT and FLOW. The main outcomes for this analysis were the composite endpoint of time to cardiovascular death or first worsening heart failure event (defined as hospitalisation or urgent visit due to heart failure), time to first worsening heart failure event, and time to cardiovascular death. Efficacy and safety endpoints were analysed with the full analysis set (ie, all participants randomly assigned to treatment, according to the intention-to-treat principle). The SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM trials are registered at ClinicalTrials.gov, NCT03574597, NCT03819153, NCT04788511, and NCT04916470, respectively, and all are complete. FINDINGS: Across the four trials, 3743 (16·8%) of 22 282 participants had a history of HFpEF (1914 assigned to semaglutide and 1829 assigned to placebo). In this group of participants with HFpEF, semaglutide reduced the risk of the combined endpoint of cardiovascular death or heart failure events (103 [5·4%] of 1914 in the semaglutide group had events vs 138 [7·5%] of 1829 in the placebo group; hazard ratio [HR] 0·69 [95% CI 0·53-0·89]; p=0·0045). Semaglutide also reduced the risk of worsening heart failure events (54 [2·8%] vs 86 [4·7%]; HR 0·59 [0·41-0·82]; p=0·0019). No significant effect on cardiovascular death alone was seen (59 [3·1%] vs 67 [3·7%]; HR 0·82 [0·57-1·16]; p=0·25). A lower proportion of patients treated with semaglutide had serious adverse events than did those who were treated with placebo (572 [29·9%] vs 708 [38·7%]). INTERPRETATION: In patients with HFpEF, semaglutide reduced the risk of the combined endpoint of cardiovascular death or worsening heart failure events, and worsening heart failure events alone, whereas its effect on cardiovascular death alone was not significant. These data support the use of semaglutide as an efficacious therapy to reduce the risk of clinical heart failure events in patients with HFpEF, for whom few treatment options are currently available. FUNDING: Novo Nordisk.
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Agonistas Receptor de Péptidos Similares al Glucagón , Péptidos Similares al Glucagón , Insuficiencia Cardíaca , Volumen Sistólico , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Péptidos Similares al Glucagón/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/mortalidad , Hospitalización/estadística & datos numéricos , Obesidad/tratamiento farmacológico , Resultado del Tratamiento , Agonistas Receptor de Péptidos Similares al Glucagón/uso terapéuticoAsunto(s)
Péptidos Similares al Glucagón , Insuficiencia Cardíaca , Obesidad , Calidad de Vida , Volumen Sistólico , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Obesidad/tratamiento farmacológico , Volumen Sistólico/efectos de los fármacos , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversosAsunto(s)
Péptidos Similares al Glucagón , Insuficiencia Cardíaca , Obesidad , Calidad de Vida , Volumen Sistólico , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Volumen Sistólico/efectos de los fármacos , Obesidad/tratamiento farmacológico , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Resultado del TratamientoRESUMEN
SOURCE CITATION: Perkovic V, Tuttle KR, Rossing P, et al; FLOW Trial Committees and Investigators. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med. 2024;391:109-121. 38785209.
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Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Hipoglucemiantes , Insuficiencia Renal Crónica , 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 Renal Crónica/complicaciones , Hipoglucemiantes/uso terapéutico , Nefropatías Diabéticas/prevención & control , Masculino , Persona de Mediana Edad , FemeninoRESUMEN
The rising prevalence of obesity is of major concern. There are currently 5 Food and Drug Administration-approved medications for the treatment of obesity: orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide 3.0 mg, and semaglutide 2.4 mg. Surgical options such as bariatric surgery and endoscopic surgery induce more durable weight loss than pharmacotherapy or lifestyle interventions alone. However, patients often experience weight regain and weight loss plateau after surgery. The addition of multimodal or multihormonal pharmacotherapy is a promising tool to address these challenges. The optimal timing of obesity pharmacotherapy with surgical and endoscopic interventions requires further investigation.
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Fármacos Antiobesidad , Naltrexona , Obesidad , Pérdida de Peso , Humanos , Fármacos Antiobesidad/uso terapéutico , Naltrexona/uso terapéutico , Cirugía Bariátrica/métodos , Orlistat/uso terapéutico , Fentermina/uso terapéutico , Liraglutida/uso terapéutico , Bupropión/uso terapéutico , Topiramato/uso terapéutico , Péptidos Similares al Glucagón/uso terapéuticoRESUMEN
PURPOSE OF REVIEW: Pediatric obesity is a growing epidemic. Lifestyle modifications remain central to obesity treatment, however pharmacologic options have gained traction, particularly glucagon-like peptide-1 receptor agonists (GLP-1RA). This review aims to summarize evidence on the use of GLP-1RAs in the management of pediatric obesity, physiological mechanisms of action of GLP-1RAs and their role in appetite regulation and glucose homeostasis and address the challenges and special considerations surrounding GLP-1RA use. RECENT FINDINGS: Recent studies have highlighted the efficacy of GLP-1RAs, such as exenatide, liraglutide, and semaglutide, in promoting weight loss and improving metabolic parameters in children and adolescents. GLP-1RA's efficacy extends beyond glycemic control to include weight loss mechanisms such as delayed gastric emptying (gastroparesis), and appetite suppression. Semaglutide, the newest GLP-1RA, holds potential for substantial weight loss in adolescents and demonstrates a similar safety and efficacy as seen in adults. SUMMARY: GLP-1RAs may offer a promising adjunct therapy for pediatric obesity, particularly in cases where lifestyle interventions alone are insufficient. However, further research is needed to elucidate long-term safety and efficacy outcomes and to address potential disparities in access to care. Overall, this review highlights the relevance and timeliness of incorporating GLP-1RAs into the comprehensive management of pediatric obesity.
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Exenatida , Receptor del Péptido 1 Similar al Glucagón , Péptidos Similares al Glucagón , Obesidad Infantil , Humanos , Niño , Obesidad Infantil/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/análogos & derivados , Adolescente , Exenatida/uso terapéutico , Liraglutida/uso terapéutico , Pérdida de Peso/efectos de los fármacos , Resultado del Tratamiento , Fármacos Antiobesidad/uso terapéutico , Ponzoñas/uso terapéuticoRESUMEN
Importance: Limited data are available on long-term weight loss achieved with semaglutide or liraglutide for type 2 diabetes (T2D) or obesity in clinical practice. Objective: To document weight loss achieved with injectable forms of semaglutide or liraglutide and identify factors associated with weight reduction of 10% or greater at 1 year. Design, Setting, and Participants: This retrospective cohort study used electronic health records from a large, integrated health system in Ohio and Florida. Participants included adults with a body mass index (calculated as the weight in kilograms divided by the height in meters squared) of at least 30.0 who initiated treatment with semaglutide or liraglutide between July 1, 2015, and June 30, 2022. Follow-up was completed July 28, 2023. Exposure: Injectable forms of semaglutide or liraglutide approved for T2D or obesity. Main Outcomes and Measures: Percentage weight change and categorical weight reduction of 10% or greater at 1 year. Results: A total of 3389 patients (mean [SD] age, 50.4 [12.2] years; 1835 [54.7%] female) were identified. Of these, 1341 patients received semaglutide for T2D; 1444, liraglutide for T2D; 227, liraglutide for obesity; and 377, semaglutide for obesity. Mean (SD) percentage weight change at 1 year was -5.1% (7.8%) with semaglutide vs -2.2% (6.4%) with liraglutide (P < .001); -3.2% (6.8%) for T2D as a treatment indication vs -5.9% (9.0%) for obesity (P < .001); and -5.5% (7.5%) with persistent medication coverage (ie, a cumulative gap of less than 90 days) at 1 year vs -2.8% (7.0%) with 90 to 275 medication coverage days and -1.8% (6.7%) with fewer than 90 medication coverage days (P < .001). In the multivariable model, semaglutide vs liraglutide (adjusted odds ratio [AOR], 2.19 [95% CI, 1.77-2.72]), obesity as a treatment indication vs T2D (AOR, 2.46 [95% CI, 1.83-3.30]), persistent medication coverage vs 90 medication coverage days (AOR, 3.36 [95% CI, 2.52-4.54]) or 90 to 275 medication coverage days within the first year (AOR, 1.50 [95% CI, 1.10-2.06]), high dosage of the medication vs low (AOR, 1.58 [95% CI, 1.11-2.25]), and female sex (AOR, 1.57 [95% CI, 1.27-1.94]) were associated with achieving a 10% or greater weight reduction at year 1. Conclusions and Relevance: In this retrospective cohort study of 3389 patients with obesity, weight reduction at 1 year was associated with the medication's active agent, its dosage, treatment indication, persistent medication coverage, and patient sex. Future research should focus on identifying the reasons for discontinuation of medication use and interventions aimed at improving long-term persistent coverage.
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Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Hipoglucemiantes , Liraglutida , Obesidad , Pérdida de Peso , Humanos , Liraglutida/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Pérdida de Peso/efectos de los fármacos , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/análogos & derivados , Estudios Retrospectivos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Adulto , Anciano , Ohio , Índice de Masa Corporal , FloridaRESUMEN
BACKGROUND: The reward-regulatory properties of GLP-1 are attracting increasing interest. Animal studies show that GLP-1 receptor agonists not only reduce consumption of addictive substances, but also influence sexual behaviour. We aimed to investigate the effect of dulaglutide versus placebo on sexual desire in humans. METHODS: In this randomised, double-blind, placebo-controlled crossover trial, healthy eugonadal men of normal weight, aged 18-50 years with active and satisfactory sex lifes were (1:1) randomly allocated to dulaglutide or placebo for four weeks. We assessed sexual desire (Massachusetts General Hospital-Sexual Functioning Questionnaire [MGH-SFQ]), hormones of the hypothalamic-pituitary-gonadal axis (total testosterone, follicle-stimulating hormone [FSH], luteinizing hormone [LH]) and sperm parameters. Changes in these parameters were compared under dulaglutide versus placebo using paired t-tests. FINDINGS: 24 out of 26 randomised participants completed the study (13 participants randomised to dulaglutide first and 13 to placebo first). No change in the MGH-SFQ was observed after four weeks of dulaglutide versus placebo (estimated difference 0.58 [95% CI -0.83 to 2.00], p-value = 0.402). Hormones of the hypothalamic-pituitary-gonadal axis (estimated differences: total testosterone (nmol/l) 0.9 [95% CI -1.5 to 3.3], FSH (IU/l) -0.2 [95% CI -0.3 to 0.0] and LH (IU/l) -0.8 [95% CI -1.5 to 0.0]) as well as sperm parameters all remained in the normal range without significant differences between the treatments. No severe adverse events occurred. INTERPRETATION: In this study of healthy men, we found no evidence of negative impacts of a four-week treatment with the widely used GLP-1 receptor agonist dulaglutide on sexual desire, hypothalamic-pituitary-gonadal axis hormones or sperm parameters. FUNDING: Swiss National Science Foundation (PZ00P3_193206), Gottfried and Julia Bangerter-Rhyner Foundation, Goldschmidt-Jacobson Foundation, Swiss Academy of Medical Sciences.
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Estudios Cruzados , Receptor del Péptido 1 Similar al Glucagón , Péptidos Similares al Glucagón , Fragmentos Fc de Inmunoglobulinas , Proteínas Recombinantes de Fusión , Humanos , Masculino , Fragmentos Fc de Inmunoglobulinas/farmacología , Péptidos Similares al Glucagón/análogos & derivados , Péptidos Similares al Glucagón/farmacología , Péptidos Similares al Glucagón/uso terapéutico , Adulto , Receptor del Péptido 1 Similar al Glucagón/agonistas , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Proteínas Recombinantes de Fusión/farmacología , Persona de Mediana Edad , Adulto Joven , Método Doble Ciego , Adolescente , Testosterona/análogos & derivados , Hormona Luteinizante/sangreRESUMEN
BACKGROUND: Older adults with type 2 diabetes mellitus (T2DM) or prediabetes are at increased risk of adverse changes in body composition, physical function, and aging-related biomarkers compared to those with normal glucose tolerance. Semaglutide is a glucagon-like peptide 1 receptor agonist that has been approved for T2DM and chronic weight management. Although semaglutide is effective for weight loss and T2DM management, its effects on lean body mass, physical function, and biomarkers of aging are understudied in older adults. OBJECTIVE: This study aims to compare the effects of lifestyle counseling with and that without semaglutide on body composition, physical function, and biomarkers of aging in older adults. METHODS: This is an open-label randomized controlled trial. A total of 20 adults (aged 65 years and older) with elevated BMI (27-40 kg/m2) and prediabetes or well-controlled T2DM (hemoglobin A1c 5.7%-7.5%) are recruited, stratified by sex, and randomized 1:1 to one of 2 groups (semaglutide plus lifestyle counseling vs lifestyle counseling alone) and followed up for 5 months. Those in the semaglutide group are titrated to 1 mg weekly, as tolerated, for 12 weeks. Lifestyle counseling is given by registered dietitians and based on the Diabetes Prevention Program Lifestyle Change Program. Our primary outcomes include changes in lean mass, physical function, and biomarkers of aging. Body composition is measured by dual-energy x-ray absorptiometry and includes total fat mass and lean mass. Physical function is measured by 6-minute walk distance, grip strength, and short physical performance battery. Biomarkers of aging are measured in blood, skeletal muscle, and abdominal adipose tissue to include C-reactive protein, interleukin-6, tumor necrosis factors α, and ß galactosidase staining. RESULTS: The study was funded in December 2021 with a projected data collection period from spring 2023 through summer 2024. CONCLUSIONS: Despite the elevated risk of adverse changes in body composition, physical function, and biomarkers of aging among older adults with glucose intolerance and elevated adiposity, the benefits and risks of commonly prescribed antihyperglycemic or weight loss medications such as semaglutide are understudied. This study aims to fill this knowledge gap to inform clinicians about the potential for additional clinically meaningful, nonglycemic effects of semaglutide. TRIAL REGISTRATION: ClinicalTrials.gov NCT05786521; https://clinicaltrials.gov/study/NCT05786521. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/62667.
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Biomarcadores , Composición Corporal , Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Resistencia a la Insulina , Sobrepeso , Humanos , Composición Corporal/efectos de los fármacos , Anciano , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/farmacología , Masculino , Biomarcadores/sangre , Femenino , Sobrepeso/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Envejecimiento/efectos de los fármacos , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Estado Prediabético/tratamiento farmacológico , Estado Prediabético/sangre , Rendimiento Físico FuncionalRESUMEN
In addition to optimal glycemic control and management of other factors aggravating the pathology (hypertension, dyslipidemia, -obesity), the cornerstone of treatment of diabetic kidney disease (DKD) includes blockers of the renin-angiotensin system, sodium-glucose cotransporter 2 inhibitors or nonsteroidal antagonists of the mineralocorticoid receptor (finerenone). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recommended in the treatment of high-risk patients with type 2 diabetes (T2DM) to reduce cardiovascular (CV) risk. Data from CV studies indicate a nephroprotective effect of certain GLP-1 RAs in T2DM patients with DKD. The FLOW study published in May 2024, analyzing the impact of semaglutide vs placebo on renal events as primary outcome, confirms this renal protection of GLP-1 RAs.
Outre le contrôle glycémique et la prise en charge d'autres facteurs d'aggravation de la pathologie, la pierre angulaire du traitement de la maladie rénale diabétique (MRD) comprend les bloqueurs du système rénine-angiotensine, les inhibiteurs du cotransporteur sodium-glucose de type 2 ou encore la finérénone (antagoniste de l'aldostérone). Les agonistes du récepteur du glucagon-like peptide-1 (ARGLP-1) sont recommandés dans le traitement des patients avec un diabète de type 2 (DT2) à haut risque afin de réduire le risque cardiovasculaire (CV). Les données provenant des études CV indiquent un effet néphroprotecteur de certains ARGLP-1 chez les patients DT2 avec MRD. L'étude FLOW, publiée fin mai 2024 et analysant l'impact du sémaglutide sur les événements rénaux comme critère principal, confirme cette protection rénale des ARGLP-1.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Receptor del Péptido 1 Similar al Glucagón , Humanos , Receptor del Péptido 1 Similar al Glucagón/agonistas , Nefropatías Diabéticas/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/farmacología , Enfermedades Cardiovasculares/prevención & control , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/fisiología , Agonistas Receptor de Péptidos Similares al GlucagónRESUMEN
Background: Semaglutide is a glucagon-like peptide-1 receptor agonists (GLP-1-RAs) approved for the treatment of type 2 diabetes mellitus (T2DM) at doses up to 1 mg. The results from randomized control trials and real-world studies revealed that weekly semaglutide was associated with significant improvements in HbA1c and body weight. To our knowledge, no study assessed the effectiveness of using semaglutide for patients with T2DM in the Saudi population. We aim to assess the effectiveness of once weekly SC 0.5 and 1 mg of semaglutide on HbA1c and weight reduction in patients with T2DM in the Saudi population within 12 months of use, evaluate the predictors of response, and compare the effect of the two doses. Method: This is a retrospective cohort study conducted at Security Force Hospital in Riyadh, Saudi Arabia. Using electronic medical records of patients with type two diabetes who received semaglutide 0.5 or 1 mg for a total duration of at least 12 months of use. Results: Within the study period of semaglutide use, HbA1c significantly decreased from baseline by -2.1% (-2.3 to -1.91, 95% CI) (P <0.001). While the mean change in weight was -6.19 kg (-6.66 to -5.72, 95% CI) (P<0.001). Moreover, BMI, FBG, total cholesterol, LDL, and TG all decreased significantly from baseline (p<0.001). When comparing the sub-groups of 0.5 and 1 mg doses, although results were numerically favorable of 1 mg, there were no statistically significant differences in HbA1c % (-2.1 ± 1.8 vs. -2.1 ± 1.9, p-value= 0.934, respectively), and weight (-6.1 ± 5 vs. -6.2 ± 4.4 kg, p-value=0.837, respectively). Significant predictors of HbA1c reduction were the duration of DM, baseline HbA1c, and insulin therapy. While the significant predictor for weight reduction was insulin therapy. Conclusion: This study is document the effectiveness of once-weekly SC semaglutide on glycemic control and weight loss in real-world practice. We recommend a starting goal dose of 0.5 mg and gradual increase of dose based individual patient response. further studies are needed to assess the effectiveness and tolerability of various semagltude doses.
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Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Hemoglobina Glucada , Hipoglucemiantes , Humanos , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/administración & dosificación , Hemoglobina Glucada/análisis , Arabia Saudita/epidemiología , Adulto , Anciano , Resultado del Tratamiento , Glucemia/efectos de los fármacos , Glucemia/análisis , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Pérdida de Peso/efectos de los fármacosRESUMEN
Obesity is an epidemic worldwide. Overweight and multiple obesity-related mechanisms, including dysmetabolic alterations, contribute to cardiovascular deleterious effects. Hence, overweight and obesity have been independently associated with increased cardiovascular risk, whose assessment is crucial for preserving life quality and reducing mortality, and to address appropriate therapeutic strategies in obese patients. Beyond the standard of care in managing overweight and obesity in adults (i.e., diet and physical exercise), several relevant pharmacotherapies have been approved, and several procedures and device types for weight loss have been recommended. In such a contest, medical weight management remains one option for treating excess weight. Most drugs used for obesity reduce appetite and increase satiety and, secondarily, slow gastric emptying to reduce body weight and, therefore, act also to improve metabolic parameters. In this contest, agonists of the glucagon-like peptide-1 receptor (GLP-1RAs) modulate different metabolic pathways associated with glucose metabolism, energy homeostasis, antioxidation, and inflammation. Moreover, this class of drugs has shown efficacy in improving glycemic control, reducing the incidence of cardiovascular events in type 2 diabetic patients, and reducing body weight independently of the presence of diabetes. Recently, in overweight or obese patients with pre-existing cardiovascular disease but without diabetes, the GLP-1RA semaglutide reduced the incidence of cardiovascular and cerebrovascular events and death from cardiovascular causes. Thus, semaglutide has been approved for secondary prevention in obese people with cardiovascular disease. Nevertheless, whether this class of drugs is equally effective for primary prevention in obese people has to be demonstrated. In this review, we will summarize updates on the pathophysiology of obesity, the effects of obesity on cardiovascular risk, the impact of different obesity phenotypes on cardiovascular diseases, and the novelties in the clinical management of obesity for cardiovascular prevention.
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Enfermedades Cardiovasculares , Factores de Riesgo de Enfermedad Cardiaca , Obesidad , Humanos , Obesidad/complicaciones , Obesidad/fisiopatología , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/etiología , Receptor del Péptido 1 Similar al Glucagón/agonistas , Péptidos Similares al Glucagón/uso terapéutico , Fármacos Antiobesidad/uso terapéutico , Pérdida de PesoRESUMEN
BACKGROUND: Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure. METHODS: The SELECT trial was a randomised, double-blind, multicentre, placebo-controlled, event-driven phase 3 trial in 41 countries. Adults aged 45 years and older, with a BMI of 27 kg/m2 or greater and established cardiovascular disease were eligible for the study. Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo. In a prespecified analysis, we examined the effect of semaglutide compared with placebo in patients with and without a history of heart failure at enrolment, subclassified as heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, or unclassified heart failure. Endpoints comprised MACE (a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death); a composite heart failure outcome (cardiovascular death or hospitalisation or urgent hospital visit for heart failure); cardiovascular death; and all-cause death. The study is registered with ClinicalTrials.gov, NCT03574597. FINDINGS: Between Oct 31, 2018, and March 31, 2021, 17â604 patients with a mean age of 61·6 years (SD 8·9) and a mean BMI of 33·4 kg/m2 (5·0) were randomly assigned to receive semaglutide (8803 [50·0%] patients) or placebo (8801 [50·0%] patients). 4286 (24·3%) of 17â604 patients had a history of investigator-defined heart failure at enrolment: 2273 (53·0%) of 4286 patients had heart failure with preserved ejection fraction, 1347 (31·4%) had heart failure with reduced ejection fraction, and 666 (15·5%) had unclassified heart failure. Baseline characteristics were similar between patients with and without heart failure. Patients with heart failure had a higher incidence of clinical events. Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19). Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint) and heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint), although patients with heart failure with reduced ejection fraction had higher absolute event rates than those with heart failure with preserved ejection fraction. For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use. Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype. INTERPRETATION: In patients with atherosclerotic cardiovascular diease and overweight or obesity, treatment with semaglutide 2·4 mg reduced MACE and composite heart failure endpoints compared with placebo in those with and without clinical heart failure, regardless of heart failure subtype. Our findings could facilitate prescribing and result in improved clinical outcomes for this patient group. FUNDING: Novo Nordisk.
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Péptidos Similares al Glucagón , Insuficiencia Cardíaca , Obesidad , Humanos , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/efectos adversos , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Método Doble Ciego , Anciano , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Volumen Sistólico/efectos de los fármacos , Resultado del Tratamiento , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Inyecciones SubcutáneasRESUMEN
In this editorial, we comment on Yin et al's recently published Letter to the editor. In particular, we focus on the potential use of glucagon-like peptide 1 receptor agonists (GLP-1RAs) alone, but even more so in combination therapy, as one of the most promising therapies in metabolic dysfunction-associated steatotic liver disease (MASLD), the new definition of an old condition, non-alcoholic fatty liver disease, which aims to better define the spectrum of steatotic pathology. It is well known that GLP-1RAs, having shown outstanding performance in fat loss, weight loss, and improvement of insulin resistance, could play a role in protecting the liver from progressive damage. Several clinical trials have shown that, among GLP-1RAs, semaglutide is a safe, well-studied therapeutic choice for MASLD patients; however, most studies demonstrate that, while semaglutide can reduce steatosis, including steatohepatitis histological signs (in terms of inflammatory cell infiltration and hepatocyte ballooning), it does not improve fibrosis. Combinations of therapies with different but complementary mechanisms of action are considered the best way to improve efficiency and slow disease progression due to the complex pathophysiology of the disease. In particular, GLP-1RAs associated with antifibrotic drug therapy, dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1RA or GLP-1 and glucagon RAs have promoted greater improvement in hepatic steatosis, liver biochemistry, and non-invasive fibrosis tests than monotherapy. Therefore, although to date there are no definitive indications from international drug agencies, there is the hope that soon the therapeutic lines in the most advanced phase of study will be able to provide a therapy for MASLD, one that will certainly include the use of GLP-1RAs as combination therapy.
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Receptor del Péptido 1 Similar al Glucagón , Péptidos Similares al Glucagón , Enfermedad del Hígado Graso no Alcohólico , Humanos , Receptor del Péptido 1 Similar al Glucagón/agonistas , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Péptidos Similares al Glucagón/uso terapéutico , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Resistencia a la Insulina , Quimioterapia Combinada/métodos , Péptido 1 Similar al Glucagón/agonistas , Péptido 1 Similar al Glucagón/metabolismo , Resultado del Tratamiento , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Progresión de la Enfermedad , Incretinas/uso terapéuticoRESUMEN
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.
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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
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.
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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
The availability of glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) such as liraglutide and semaglutide, and a GLP-1 and glucose dependent insulinotropic polypeptide coagonist (tirzepatide) represents a paradigm shift in the management of both type 2 diabetes and obesity. There is now considerable attention, including in the public media, on the effect of both long-acting and short-acting GLP-1RAs to delay gastric emptying. Although slowed gastric emptying is integral to reducing post-prandial blood glucose responses in type 2 diabetes, marked slowing of gastric emptying might also increase the propensity for longer intragastric retention of food, with a consequent increased risk of aspiration at the time of surgery or upper gastrointestinal endoscopy. This Personal View summarises current knowledge of the effects of GLP-1 and GLP-1RAs on gastrointestinal physiology, particularly gastric emptying, and discusses the implications for the development of sound pre-operative or pre-procedural guidelines. The development of pre-procedural guidelines is currently compromised by the poor evidence base, particularly in relation to the effect of long-acting GLP-1RAs on gastric emptying. We suggest pre-procedural management pathways for individuals on GLP-1RA-based therapy and discuss priorities for future research.
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Diabetes Mellitus Tipo 2 , Vaciamiento Gástrico , Receptor del Péptido 1 Similar al Glucagón , Péptidos Similares al Glucagón , Hipoglucemiantes , Humanos , Receptor del Péptido 1 Similar al Glucagón/agonistas , Vaciamiento Gástrico/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/farmacología , Obesidad/tratamiento farmacológico , Liraglutida/uso terapéutico , Liraglutida/farmacología , Péptido 1 Similar al Glucagón/agonistas , Agonistas Receptor de Péptidos Similares al GlucagónRESUMEN
BACKGROUND: Obesity has been established as a significant risk factor for osteoarthritis. Anti-obesity medications (AOMs) have demonstrated efficacy in weight management. However, potential impact on osteoarthritis risk remains uncertain. METHODS: This retrospective cohort study used Kythera data from NOV2022 to JULY2024. Patients with obesity using AOMs were identified through diagnosis and prescription claims for tirzepatide, semaglutide, or liraglutide between 1NOV2023 and 31JAN2024, with a 6-month follow-up to assess OA risk. OA risk, analyzed using Cox regression and propensity score matching, controlled for comorbidities and sociodemographic factors. RESULTS: There were 39,394 patients living with obesity using AOM (23,933 semaglutide 12,854 tirzepatide, 2,607 liraglutide) and 72,405 without AOM use. The adjusted osteoarthritis risk was 27% % lower in AOM users than in non-users (hazard ratio (HR) = 073, 95% CI (0.67-0.79), p < 0.01). Among AOMs, tirzepatide was associated with a significantly lower osteoarthritis (OA) risk compared to semaglutide (HR = 0.57, 95% CI: 0.50-0.65, p < 0.0001). Liraglutide was linked to a significantly higher OA risk vs tirzepatide (HR = 1.63, 95% CI: 1.23-2.15, p = 0.0007). CONCLUSIONS: AOM use was associated with a significantly lower risk of OA and may be an effective obesity management intervention.