Asunto(s)
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 EdadAsunto(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.
Asunto(s)
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
Postpartum mothers and their healthcare providers often face the challenge of limited data regarding the safety of drug therapies during lactation. Pregnancy can lead to sustained weight gain, and obesity can negatively impact both physical and psychological well-being. The introduction of GLP-1 agonists to augment weight loss has become a topic of interest for many postpartum mothers. Our study aims to investigate the transmission of semaglutide into human milk in the first steps to ensure the safety and health of both lactating mothers and their breastfed infants. Semaglutide quantification was performed using high-resolution liquid chromatography-mass spectrometry. InfantRisk Center Human Milk biorepository released milk samples from eight women collected at 0, 12 and 24 h post-semaglutide administration. Semaglutide was extracted using protein precipitation in methanol, followed by chromatographic separation. Linear calibration curves for the method ranged between 2.5-30 ng/mL, with a limit of detection of 1.7 ng/mL and a limit of quantification of 5.7 ng/mL (LLOQ). Semaglutide was not detected in any of the collected human milk samples. A worst-case scenario of the relative infant dose (RID) was calculated using the LLOQ as the drug concentration in milk when considering semaglutide's bioavailability and long-acting dose profile. The maximum RID projected was 1.26%, far below the standard 10% safety threshold. While questions about long-term infant outcomes, the safety of maternal nutrient intake, and the nutrient content of breast milk remain, our findings suggest that semaglutide concentrations in human milk are unlikely to pose clinical concerns for breastfed infants. These results support healthcare providers in making informed decisions regarding postpartum therapeutic interventions.
Asunto(s)
Lactancia Materna , Péptidos Similares al Glucagón , Leche Humana , Humanos , Leche Humana/química , Femenino , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/análisis , Péptidos Similares al Glucagón/efectos adversos , Recién Nacido , Adulto , Lactancia , LactanteRESUMEN
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.
Asunto(s)
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
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.
Asunto(s)
Fármacos Antiobesidad , Liraglutida , Obesidad , Osteoartritis , Humanos , Osteoartritis/tratamiento farmacológico , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Fármacos Antiobesidad/uso terapéutico , Fármacos Antiobesidad/efectos adversos , Liraglutida/uso terapéutico , Anciano , Estudios de Cohortes , Adulto , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/análogos & derivados , Péptidos Similares al Glucagón/efectos adversos , Factores de Riesgo , Estudios de SeguimientoRESUMEN
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/métodosAsunto(s)
Antipsicóticos , Péptidos Similares al Glucagón , Clorhidrato de Lurasidona , Náusea , Humanos , Clorhidrato de Lurasidona/efectos adversos , Náusea/inducido químicamente , Antipsicóticos/efectos adversos , Antipsicóticos/administración & dosificación , Péptidos Similares al Glucagón/efectos adversos , Péptidos Similares al Glucagón/administración & dosificación , Femenino , Masculino , Esquizofrenia/tratamiento farmacológico , Persona de Mediana EdadRESUMEN
Nonarteritic anterior ischemic optic neuropathy (NAION) was first documented by a French physician Jean-Pierre Saint-Yves in 1817 (19th century). The clinical description of NAION was not known until 1935 when C. Miller Fischer thoroughly described it. Briefly, NAION is a rare (2.5-11.8 per 1,00,000 cases in men above 50 years) but serious condition that causes sudden painless loss of vision due to ischemia of the optic nerve.1 It is more common in Caucasians compared with Asians and is associated with various risk factors such as hypertension, type 2 diabetes (T2D), smoking, hyperlipidemia, obesity, obstructive sleep apnea, small optic nerve cup ("disk at risk"), optic nerve drusen, and certain drugs, especially phosphodiesterase type 5 inhibitors (PDE-5I), amiodarone, and cabergoline.2 Although the clinical development programs and real-world studies of semaglutide [a glucagon-like peptide-1 receptor agonist (GLP-1RA) approved for the treatment of T2D and obesity] did not report any significant increase in the risk of NAION, a recent retrospective cohort study suggested a possible link between NAION and semaglutide.3 This editorial briefly summarizes the current knowledge about NAION and its relation to metabolic disorders, cardiovascular, and antidiabetes drugs and puts a perspective concerning semaglutide.
Asunto(s)
Péptidos Similares al Glucagón , Neuropatía Óptica Isquémica , Humanos , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Neuropatía Óptica Isquémica/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Factores de RiesgoRESUMEN
Importance: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained use primarily due to their weight-reduction effects, although a regulatory review was undertaken for potential suicidality concern. Objectives: To evaluate potential signals for suicidal and self-injurious adverse drug reactions (ADRs) associated with the GLP-1 RAs semaglutide and liraglutide. Design, Setting, and Participants: Disproportionality analysis through the case-control design using the World Health Organization (WHO) global database of suspected ADRs. Participants were clinical patients worldwide experiencing an ADR suspectedly attributable to semaglutide or liraglutide in the database from inception to August 30, 2023. Data were analyzed from September to December 2023. Exposure: Treatment with semaglutide or liraglutide regardless of indication or treatment duration. Main Outcomes and Measures: Reporting odds ratio (ROR) and the bayesian information component (IC) with 95% CIs were calculated as measures of disproportionate reporting of suicidal and self-injurious ADRs associated with semaglutide and liraglutide compared with all other medications. Sensitivity analyses were conducted including patients with coreported use of antidepressants and benzodiazepines and using dapagliflozin, metformin, and orlistat as comparators. A disproportionality signal was considered when the lower limits of the ROR and IC were above 1 and 0, respectively. Results: A total of 107 (median [IQR] age 48 [40-56] years; 59 female patients [55%]) and 162 (median [IQR] age 47 [38-60] years; 100 female patients [61%]) cases of suicidal and/or self-injurious ADRs were reported between November 2000 and August 2023 with semaglutide and liraglutide, respectively. Significant disproportionality was detected only for semaglutide-associated suicidal ideation (ROR, 1.45; 95% CI, 1.18-1.77; IC, 0.53; 95% CI, 0.19-0.78), which remained significant in patients with coreported use of antidepressants (ROR, 4.45; 95% CI, 2.52-7.86; IC, 1.96; 95% CI, 0.98-2.63) and benzodiazepines (ROR, 4.07; 95% CI, 1.69-9.82; IC, 1.67; 95% CI, 0.11-2.65), when compared with dapagliflozin (ROR, 5.56; 95% CI, 3.23-9.60; IC, 0.70; 95% CI, 0.36-0.95), metformin (ROR, 3.86; 95% CI, 2.91-5.12; IC, 1.20; 95% CI, 0.94-1.53) and orlistat (ROR, 4.24; 95% CI, 2.69-6.69; IC, 0.70; 95% CI, 0.36-0.95). Conclusions and Relevance: This study using the WHO database found a signal of semaglutide-associated suicidal ideation, which warrants urgent clarification.
Asunto(s)
Péptidos Similares al Glucagón , Hipoglucemiantes , Liraglutida , Suicidio , Organización Mundial de la Salud , Humanos , Liraglutida/uso terapéutico , Liraglutida/efectos adversos , Péptidos Similares al Glucagón/efectos adversos , Péptidos Similares al Glucagón/uso terapéutico , Femenino , Masculino , Estudios de Casos y Controles , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Suicidio/estadística & datos numéricos , Persona de Mediana Edad , Adulto , Conducta Autodestructiva/inducido químicamente , Conducta Autodestructiva/epidemiologíaRESUMEN
BACKGROUND: There are currently limited data regarding the effect of semaglutide 2·4 mg in individuals with obesity and prediabetes in clinical trials. We aimed to assess the efficacy and safety of semaglutide 2·4 mg for weight management and glycaemic control in participants with obesity and prediabetes. METHODS: STEP 10 was a randomised, double-blind, parallel-group, phase 3 trial done across 30 trial sites in Canada, Denmark, Finland, Spain, and the UK and included participants aged 18 years or older with a BMI of 30 kg/m2 or higher and prediabetes according to UK National Institute for Health and Care Excellence criteria (defined as having at least one of the following at screening: HbA1c of 6·0-6·4% [42-47 mmol/mol] or fasting plasma glucose [FPG] of 5·5-6·9 mmol/L). Participants were randomly assigned (2:1) to once-weekly subcutaneous semaglutide 2·4 mg or placebo with diet and physical activity counselling for 52 weeks, followed by a 28-week off-treatment period. Primary endpoints were percentage change in bodyweight and proportion of participants reverting to normoglycaemia (HbA1c <6·0% [<42 mmol/mol] and FPG <5·5 mmol/L) at week 52 (assessed in all randomly assigned participants by intention to treat). Selective safety data were collected for participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT05040971, and is complete. FINDINGS: Between Sept 16 and Dec 29, 2021, 138 participants were randomly assigned to semaglutide 2·4 mg and 69 to placebo. 147 (71%) were female and 60 (29%) were male; 183 (88%) were White. All randomly assigned participants received at least one dose of study drug. Baseline mean age was 53 years (SD 11), bodyweight 111·6 kg (22·2), BMI 40·1 kg/m2 (6·9), waist circumference 120·1 cm (14·7), HbA1c 5·9% (0·3; 41·3 mmol/mol [3·0]), and FPG 5·9 mmol/L (0·6). There was a significantly greater reduction in bodyweight with semaglutide 2·4 mg than with placebo at week 52 (-13·9% [SD 0·7] vs -2·7% [0·6]; estimated treatment difference -11·2% [95% CI -13·0 to -9·4]; p<0·0001). Greater proportions of participants reverted to normoglycaemia at week 52 with semaglutide 2·4 mg than with placebo (103 [81%] of 127 vs nine [14%] of 64; odds ratio 19·8 [95% CI 8·7 to 45·2]; p<0·0001). Serious adverse events occurred in 12 (9%) participants receiving semaglutide 2·4 mg versus six (9%) receiving placebo. Adverse events leading to treatment discontinuation occurred in eight (6%) participants in the semaglutide 2·4 mg group versus one (1%) participant in the placebo group. No new safety signals were reported. INTERPRETATION: Semaglutide 2·4 mg provided superior reduction in bodyweight and reversion to normoglycaemia versus placebo in participants with obesity and prediabetes. The safety and tolerability profile was consistent with previous studies and with the GLP-1 receptor agonist class. These findings support the potential use of semaglutide 2·4 mg as a treatment option for individuals with obesity and prediabetes to achieve reversion to normoglycaemia. FUNDING: Novo Nordisk. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.
Asunto(s)
Péptidos Similares al Glucagón , Obesidad , Estado Prediabético , Humanos , Masculino , Femenino , Método Doble Ciego , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Persona de Mediana Edad , Estado Prediabético/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Adulto , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Glucemia/análisis , Glucemia/efectos de los fármacos , Resultado del Tratamiento , Anciano , Pérdida de Peso/efectos de los fármacosRESUMEN
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
INTRODUCTION: The prevalence of obesity has increased worldwide over the past decades. Regional variations exist in the relationship between body mass index (BMI), body fat, and health risks: Asians typically have a lower BMI than people of European descent, but a higher risk of obesity-related comorbidities. However, there is a paucity of evidence for anti-obesity medications (AOMs) in East Asian populations. In this study, we aimed to systematically review evidence regarding the safety and efficacy of AOMs among adults with obesity disease in East Asia, and to assess the feasibility of conducting an indirect treatment comparison (ITC) between the semaglutide and mazindol trials. METHODS: The Embase, MEDLINE, and ICHUSHI databases were searched via the Ovid SP platform for randomized controlled trials, in English or Japanese, reporting data on semaglutide or mazindol therapy with placebo or diet and exercise as comparators. The potential risks of bias in conducting a population-adjusted ITC were determined based on the heterogeneity of potential effect modifiers and variations in study design. RESULTS: Of 21 publications, 2 were included in this study based on the eligibility criteria. The STEP 6 study established the clinical efficacy of subcutaneous semaglutide compared with placebo in the reduction of body weight and cardiometabolic risk factors [glycated hemoglobin (HbA1c), total cholesterol, and systolic blood pressure] among Japanese and South Korean people with obesity disease. Mazindol also proved beneficial in reducing body weight and total cholesterol compared with placebo in Japan. Both semaglutide and mazindol were associated with higher rates of adverse events and treatment discontinuation than placebo. An ITC between the two studies was not deemed feasible based on the potential risks of bias. CONCLUSIONS: Semaglutide and mazindol are associated with significant body weight reduction among people with obesity in East Asia. Further research based on label indications and up-to-date real-world data among East Asian people with obesity would help determine additional clinical benefits.
Asunto(s)
Fármacos Antiobesidad , Péptidos Similares al Glucagón , Obesidad , Humanos , Obesidad/tratamiento farmacológico , Fármacos Antiobesidad/uso terapéutico , Fármacos Antiobesidad/efectos adversos , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Asia Oriental , Adulto , Pueblo Asiatico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Índice de Masa Corporal , Pérdida de Peso/efectos de los fármacos , Pueblos del Este de AsiaRESUMEN
INTRODUCTION: Leukocytoclastic vasculitis (LCV) is a small vessel vasculitis involving arterioles, capillaries and postcapillary venules. LCV is generally confined to the skin, with extracutaneous manifestations occurring less frequently. LCV has multiple potential etiologies. Indeed, histological LCV can be found in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, immune complex vasculitis, vasculitis associated with systemic diseases (i.e. sarcoidosis, Sjögren's syndrome, rheumatoid arthritis, and systemic lupus erythematosus), or in vasculitis associated with cancer, infections, sepsis and use of certain medications. LCV can also be idiopathic in up to 50% of cases. CASE REPORT: Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist used for management of type 2 diabetes mellitus (T2DM), obesity and overweight associated with one or more weight-related comorbidities. A case of drug-induced LCV has already been described with the use of once-daily oral semaglutide. Herein, we describe the first case of skin-limited LCV induced by once-weekly subcutaneous semaglutide in a 73-year-old man with T2DM, who experienced the complete resolution of the skin lesions shortly after the discontinuation of semaglutide therapy. CONCLUSION: Future prospective studies, adverse event reporting and post-marketing surveillance will certainly contribute to establishing if LCV represents a less rare than expected side effect of both oral and subcutaneous semaglutide formulations.
Asunto(s)
Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Vasculitis Leucocitoclástica Cutánea , Humanos , Masculino , Péptidos Similares al Glucagón/efectos adversos , Péptidos Similares al Glucagón/administración & dosificación , Anciano , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Vasculitis Leucocitoclástica Cutánea/inducido químicamente , Vasculitis Leucocitoclástica Cutánea/tratamiento farmacológico , Vasculitis Leucocitoclástica Cutánea/patología , Inyecciones Subcutáneas , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/administración & dosificaciónAsunto(s)
Diabetes Mellitus Tipo 2 , Agonistas Receptor de Péptidos Similares al Glucagón , Insuficiencia Cardíaca , Hipoglucemiantes , Obesidad , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Insuficiencia Cardíaca/etiología , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Obesidad/cirugía , Agonistas Receptor de Péptidos Similares al Glucagón/efectos adversos , Agonistas Receptor de Péptidos Similares al Glucagón/uso terapéutico , Cirugía BariátricaRESUMEN
Importance: Anecdotal experience raised the possibility that semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA) with rapidly increasing use, is associated with nonarteritic anterior ischemic optic neuropathy (NAION). Objective: To investigate whether there is an association between semaglutide and risk of NAION. Design, Setting, and Participants: In a retrospective matched cohort study using data from a centralized data registry of patients evaluated by neuro-ophthalmologists at 1 academic institution from December 1, 2017, through November 30, 2023, a search for International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code H47.01 (ischemic optic neuropathy) and text search yielded 16â¯827 patients with no history of NAION. Propensity matching was used to assess whether prescribed semaglutide was associated with NAION in patients with type 2 diabetes (T2D) or overweight/obesity, in each case accounting for covarying factors (sex, age, systemic hypertension, T2D, obstructive sleep apnea, obesity, hyperlipidemia, and coronary artery disease) and contraindications for use of semaglutide. The cumulative incidence of NAION was determined with the Kaplan-Meier method and a Cox proportional hazards regression model adjusted for potential confounding comorbidities. Data were analyzed from December 1, 2017, through November 30, 2023. Exposures: Prescriptions for semaglutide vs non-GLP-1 RA medications to manage either T2D or weight. Main Outcomes and Measures: Cumulative incidence and hazard ratio of NAION. Results: Among 16â¯827 patients, 710 had T2D (194 prescribed semaglutide; 516 prescribed non-GLP-1 RA antidiabetic medications; median [IQR] age, 59 [49-68] years; 369 [52%] female) and 979 were overweight or obese (361 prescribed semaglutide; 618 prescribed non-GLP-1 RA weight-loss medications; median [IQR] age, 47 [32-59] years; 708 [72%] female). In the population with T2D, 17 NAION events occurred in patients prescribed semaglutide vs 6 in the non-GLP-1 RA antidiabetes cohort. The cumulative incidence of NAION for the semaglutide and non-GLP-1 RA cohorts over 36 months was 8.9% (95% CI, 4.5%-13.1%) and 1.8% (95% CI, 0%-3.5%), respectively. A Cox proportional hazards regression model showed higher risk of NAION for patients receiving semaglutide (hazard ratio [HR], 4.28; 95% CI, 1.62-11.29); P < .001). In the population of patients who were overweight or obese, 20 NAION events occurred in the prescribed semaglutide cohort vs 3 in the non-GLP-1 RA cohort. The cumulative incidence of NAION for the semaglutide vs non-GLP-1 RA cohorts over 36 months was 6.7% (95% CI, 3.6%-9.7%) and 0.8% (95% CI, 0%-1.8%), respectively. A Cox proportional hazards regression model showed a higher risk of NAION for patients prescribed semaglutide (HR, 7.64; 95% CI, 2.21-26.36; P < .001). Conclusions and Relevance: This study's findings suggest an association between semaglutide and NAION. As this was an observational study, future study is required to assess causality.
Asunto(s)
Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Hipoglucemiantes , Neuropatía Óptica Isquémica , Humanos , Femenino , Masculino , Estudios Retrospectivos , Péptidos Similares al Glucagón/efectos adversos , Péptidos Similares al Glucagón/uso terapéutico , Persona de Mediana Edad , Neuropatía Óptica Isquémica/inducido químicamente , Neuropatía Óptica Isquémica/epidemiología , Anciano , Incidencia , Factores de Riesgo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéuticoAsunto(s)
Péptidos Similares al Glucagón , Neuropatía Óptica Isquémica , Humanos , Neuropatía Óptica Isquémica/inducido químicamente , Neuropatía Óptica Isquémica/tratamiento farmacológico , Neuropatía Óptica Isquémica/diagnóstico , Péptidos Similares al Glucagón/efectos adversos , Péptidos Similares al Glucagón/uso terapéutico , Masculino , Femenino , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Anciano , Agudeza Visual , Persona de Mediana EdadRESUMEN
Importance: Obesity affects approximately 19% of women and 14% of men worldwide and is associated with increased morbidity. Antiobesity medications (AOMs) modify biological processes that affect appetite and significantly improve outcomes, such as type 2 diabetes, hypertension, and dyslipidemia. Observations: AOMs should be administered in combination with lifestyle interventions and can be classified according to their mechanisms of action. Orlistat modifies digestive tract absorption and causes gastrointestinal adverse effects, such as oily fecal spotting and urgency, in more than 25% of patients. Centrally acting drugs, such as phentermine-topiramate and naltrexone-bupropion, regulate appetite in the brain and are associated with constipation in approximately 20% of patients, although the incidence of other adverse effects (eg, paresthesia, nausea) varies by medication. Nutrient-stimulated hormone-based medications, such as liraglutide, semaglutide, and tirzepatide, mimic the actions of enteropancreatic hormones that modify central appetite regulation and provide multiple cardiometabolic weight-loss benefits. Adverse effects of these drugs include nausea (28%-44%), diarrhea (21%-30%), and constipation (11%-24%). The relative potency of adult obesity medications has been studied in meta-analyses. Compared with placebo, orlistat was associated with 3.1% greater weight loss (52 randomized clinical trials [RCTs]; 16â¯964 participants), phentermine-topiramate was associated with 8.0% greater weight loss (5 RCTs; 3407 participants), naltrexone-bupropion was associated with 4.1% greater weight loss (6 RCTs; 9949 participants), liraglutide was associated with 4.7% greater weight loss (18 RCTs; 6321 participants), semaglutide was associated with 11.4% greater weight loss (5 RCTs; 4421 participants), and tirzepatide 15 mg was associated with 12.4% greater weight loss (6 RCTs; 1972 participants). Conclusion and Relevance: Obesity is associated with increased morbidity. Antiobesity medications are effective adjunctive therapy to lifestyle changes for improved weight loss and health outcomes.
Asunto(s)
Fármacos Antiobesidad , Dieta Saludable , Obesidad , Femenino , Humanos , Masculino , Fármacos Antiobesidad/uso terapéutico , Fármacos Antiobesidad/efectos adversos , Bupropión/uso terapéutico , Bupropión/efectos adversos , Combinación de Medicamentos , Fructosa/análogos & derivados , Fructosa/uso terapéutico , Fructosa/efectos adversos , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Lactonas/uso terapéutico , Lactonas/efectos adversos , Liraglutida/uso terapéutico , Liraglutida/efectos adversos , Naltrexona/uso terapéutico , Naltrexona/efectos adversos , Obesidad/dietoterapia , Obesidad/tratamiento farmacológico , Orlistat/uso terapéutico , Fentermina/uso terapéutico , Fentermina/efectos adversos , Topiramato/uso terapéutico , Topiramato/efectos adversos , Pérdida de Peso/efectos de los fármacos , Terapia Combinada/métodosRESUMEN
BACKGROUND: Semaglutide is increasingly used in the management of type 2 diabetes mellitus and obesity. Ensuring the safety of this medication is crucial for its clinical use. This meta-analysis evaluates the safety profile of semaglutide across patient populations and treatment durations. METHODS: Randomized controlled trials assessing the safety of semaglutide vs. placebo, with specified treatment durations were identified. The primary outcome was occurrence of any cardiovascular adverse events. Secondary outcomes included sudden cardiac death, adverse events leading to death, adverse events, gastrointestinal side effects, occurrence of hypoglycemia, and new-onset neoplasm. RESULTS: A total of 23 studies met the inclusion criteria with a combined sample size of 57,911 participants. The meta-analysis revealed that the adverse event associated with semaglutide is gastrointestinal in nature (nausea and vomiting). No significant differences were observed between semaglutide and comparator groups. CONCLUSION: Semaglutide appears to have a favorable safety profile across diverse patient populations and treatment durations, supporting its continued use in the management of type 2 diabetes mellitus and obesity. It is generally well-tolerated, with a low incidence of adverse events. Clinicians should be aware of these findings and monitor patients accordingly. Further long-term studies are warranted to assess the safety of semaglutide in clinical practice.