RESUMO
OBJECTIVES: The objective of this study was to evaluate the effectiveness of the combined use of empagliflozin (EMPA) and topiramate (TPM) versus a placebo in overweight/obese individuals without diabetes on a calorie-restricted diet. METHODS: In this study, 44 non-diabetic and overweight/obese subjects who were on a calorie restricted diet were randomly assigned into 2 groups: (1) Participants received a 10 mg EMPA tablet daily plus TPM tablet (at the 1st week 25 mg once a day and from the second week 25 mg twice a day); (2) Participants received an empagliflozin placebo (daily) plus a topiramate placebo (as mentioned for topiramate tablet in group 1), for 12 weeks. At baseline and weeks 4, 8, 12, weight, height, body mass index (BMI), waist circumference (WC), and body composition were evaluated. Before and after the intervention, blood pressure, C reactive protein, and glucose and lipid profile parameters were measured. RESULTS: The EMPA/TPM group, compared to placebo, had a greater percent change of weight at week 12 (- 8.92 ± 1.80 vs. - 4.93 ± 1.17). The intervention group had a greater percent change of fat mass and fat percent at week 12 (P < 0.05). However, there was no difference in the percent of change in fat-free percent between the two groups at week 12 (P = 0.577). Within-group analysis found a significant reduction in SBP, DBP, FBS, insulin, HOMA-IR, TC, LDL, HDL, TG, and CRP in both groups (P < 0.05). At week 12, no statistically significant difference was observed between the two groups in any of mentioned variables (P > 0.05). CONCLUSION: In non-diabetic overweight/obese individuals, the combination of EMPA/TPM and calorie restriction led to a notable decrease in body weight and was generally well-tolerated. Further research is required to evaluate the potential advantages of utilizing this combination for sustained weight management in the long run. LEVEL I: Randomized clinical trial.
Assuntos
Compostos Benzidrílicos , Restrição Calórica , Glucosídeos , Obesidade , Sobrepeso , Topiramato , Humanos , Compostos Benzidrílicos/uso terapêutico , Glucosídeos/uso terapêutico , Masculino , Feminino , Adulto , Obesidade/tratamento farmacológico , Obesidade/dietoterapia , Obesidade/complicações , Sobrepeso/tratamento farmacológico , Sobrepeso/dietoterapia , Topiramato/uso terapêutico , Pessoa de Meia-Idade , Índice de Massa Corporal , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , Quimioterapia Combinada , Método Duplo-Cego , Fármacos Antiobesidade/uso terapêutico , Composição Corporal/efeitos dos fármacos , Circunferência da Cintura/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Resultado do Tratamento , Redução de Peso/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêuticoRESUMO
Chronic rhinosinusitis with nasal polyps (CRSwNP) significantly impacts quality of life and often presents therapeutic challenges, with biologics like dupilumab showing promise in managing severe, uncontrolled cases. The aim of this study was to assess the influence of overweight on the effectiveness of dupilumab in patients with uncontrolled CRSwNP. This retrospective study analyzed treatment outcomes of 75 CRSwNP patients receiving dupilumab, categorizing them into underweight/normal-weight (BMI ≤ 24.9 kg/m2) and overweight/obese (BMI ≥ 25 kg/m2) groups. Outcome measures included changes in nasal polyp score (NPS) and sinonasal outcome test (SNOT-22) scores. Results demonstrated that the underweight/normal-weight group experienced significantly greater improvements in NPS and a higher rate of total NPS improvement compared to the overweight/obese group. While SNOT-22 scores improved in both groups, no significant differences were observed. Among patients with comorbid asthma, the underweight/normal-weight subgroup also showed significantly better outcomes, including greater reductions in both NPS and SNOT-22 scores. Multiple regression analysis identified BMI as an independent prognostic factor for NPS outcomes. The findings suggest that overweight/obesity adversely affects the response to dupilumab in CRSwNP, emphasizing the need for personalized treatment strategies considering BMI.
Assuntos
Anticorpos Monoclonais Humanizados , Índice de Massa Corporal , Pólipos Nasais , Sobrepeso , Rinite , Sinusite , Humanos , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/complicações , Masculino , Feminino , Sinusite/tratamento farmacológico , Sinusite/complicações , Anticorpos Monoclonais Humanizados/uso terapêutico , Estudos Retrospectivos , Pessoa de Meia-Idade , Rinite/tratamento farmacológico , Rinite/complicações , Doença Crônica , Sobrepeso/complicações , Sobrepeso/tratamento farmacológico , Adulto , Resultado do Tratamento , Obesidade/complicações , Obesidade/tratamento farmacológico , Idoso , Qualidade de Vida , RinossinusiteRESUMO
OBJECTIVE: Type 2 diabetes (T2D) mellitus is increasing exponentially in India, with overweight/obesity being prime contributors. This study aimed at assessing the clinical impact of the combination therapy of a glucagon-like peptide-1 receptor agonist (GLP-1RA) injection (inj.) and a sodium-glucose cotransporter-2 inhibitor (SGLT-2i) in overweight/obese patients from the Indian subcontinent. METHODS: In two real-world evidence (RWE) studies (RWE1 and 2), we retrospectively observed the effect of the combination therapy of a GLP-1RA, injection dulaglutide (DU) 1.5 mg/week, and an SGLT-2i, canagliflozin (CAN) 100 mg/day at weeks 16, 32, and 52 on HbA1c, body weight (weight), systolic blood pressure (SBP), lipids, change in doses of antidiabetic agents (ADA) and antihypertensive agents (AHA) in overweight/obese Asian Indian subjects with T2D, who had suboptimal glycemic control. RESULTS: A total of 95 T2D patients [51 males (M), 44 females (F)] completed the two RWE studies. In RWE 1, 40 patients (20 M/20 F), mean [standard deviation (SD)] age 49.4 (10.7) years (Y), weight 92.6 (6.6) kg, body mass index (BMI) 30.6 (2.3) kg/m2, duration of T2D 8.1 (3.2) Y, completed the study. At week 32, the mean (SD) reduction in A1c (%) was -1.3% [8.4 (0.7) to 7.1 (0.3); p < 0.01] and mean (SD) weight (kg) loss was -5.5 [92.6 (6.6) to 87.9 (7.02); p < 0.00001]. This group was then followed up until week 52. In RWE 2, 55 patients (31 M/24 F), age 51 (5.8) Y, weight 92.6 ± 3.4 kg, BMI 31.1 ± 2.1 kg/m2, SBP 142.4 ± 3.9 mm Hg, estimated glomerular filtration rate (eGFR) 62 ± 5 mL/minute/1.73 m2, with 8.4 ± 3.3 Y duration of diabetes met the inclusion criteria. In 71% of subjects, A1c decreased by -1.4% [8.5 ± 0.4 to 7.1 ± 0.2; p < 0.0001] at week 16 and was 6.8 ± 0.3 (p = 0.0002) in 18% at week 32. CONCLUSION: A statistically significant (SS) improvement in glycemic control, weight, and improvement in cardiovascular (CV) risk factors was observed with the GLP-1RA/SGLT-2i combination, which was well tolerated.
Assuntos
Canagliflozina , Diabetes Mellitus Tipo 2 , Quimioterapia Combinada , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hipoglicemiantes , Obesidade , Sobrepeso , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Masculino , Feminino , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Pessoa de Meia-Idade , Índia , Obesidade/tratamento farmacológico , Obesidade/complicações , Sobrepeso/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/administração & dosagem , Canagliflozina/uso terapêutico , Canagliflozina/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/uso terapêutico , Adulto , Estudos Retrospectivos , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Hemoglobinas Glicadas/análise , Resultado do Tratamento , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Fragmentos Fc das ImunoglobulinasRESUMO
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.
Assuntos
Biomarcadores , Composição Corporal , Diabetes Mellitus Tipo 2 , Peptídeos Semelhantes ao Glucagon , Resistência à Insulina , Sobrepeso , Humanos , Composição Corporal/efeitos dos fármacos , Idoso , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Peptídeos Semelhantes ao Glucagon/farmacologia , Masculino , Biomarcadores/sangue , Feminino , Sobrepeso/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Envelhecimento/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Estado Pré-Diabético/tratamento farmacológico , Estado Pré-Diabético/sangue , Desempenho Físico FuncionalRESUMO
OBJECTIVE: The prevalence of overweight and obesity among beneficiaries of the Military Health System (MHS) is 41.6% and 30.5%, respectively. This incurs significant medical, fiscal, and military readiness costs. It is not currently known how the utilization of antiobesity medications (AOMs) within the MHS compares with that in the Veterans Health Administration or the private sector. Our aim was to assess the utilization of AOMs within the MHS. METHODS: A cross-sectional study was conducted using data gathered from the MHS Data Repository and the inclusion of all adult TRICARE Prime and Plus beneficiaries ages 18 to 64 years who were prescribed at least one TRICARE-approved AOM during the years 2018 to 2022. RESULTS: The total study population included 4,414,127 beneficiaries, of whom 1,871,780 were active-duty service members. The utilization of AOMs among the eligible population was 0.56% (0.44% among active-duty personnel). Liraglutide was the most-prescribed AOM (36% of the total). Female sex, age greater than or equal to 30 but less than 60 years, and enlisted or warrant officer rank were all associated with statistically significant higher odds of receiving AOMs. CONCLUSIONS: Comparable with the US private sector, the MHS significantly underutilizes AOMs, including among active-duty service members, despite coverage of AOMs since 2018.
Assuntos
Fármacos Antiobesidade , Obesidade , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Estudos Transversais , Fármacos Antiobesidade/uso terapêutico , Estados Unidos/epidemiologia , Obesidade/epidemiologia , Obesidade/tratamento farmacológico , Adulto Jovem , Adolescente , Militares/estatística & dados numéricos , Liraglutida/uso terapêutico , Saúde Militar/estatística & dados numéricos , Sobrepeso/epidemiologia , Sobrepeso/tratamento farmacológico , Setor Privado/estatística & dados numéricos , United States Department of Veterans Affairs/estatística & dados numéricos , PrevalênciaRESUMO
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.
Assuntos
Glicemia , Índice de Massa Corporal , Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Peptídeos Semelhantes ao Glucagon , Hemoglobinas Glicadas , Hipoglicemiantes , Metformina , Obesidade , Sobrepeso , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Masculino , Pessoa de Meia-Idade , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Hemoglobinas Glicadas/efeitos dos fármacos , Hemoglobinas Glicadas/análise , Obesidade/tratamento farmacológico , Obesidade/complicações , Metformina/uso terapêutico , Sobrepeso/tratamento farmacológico , Sobrepeso/complicações , Glicemia/efeitos dos fármacos , Glicemia/análise , Idoso , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Análise de Variância , Adulto , Quimioterapia Combinada , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Proteínas Recombinantes de FusãoRESUMO
Polyphenols exert beneficial effects on host metabolism, which may be mediated by the gut microbiota. We investigated sex-specific differences in microbiota composition and interactions with cardiometabolic parameters after polyphenol supplementation in individuals with overweight/obesity. In a double-blind, randomized, placebo-controlled trial, 19 women and 18 men with normal glucose tolerance and body mass index >25 kg/m2 received epigallocatechin-3-gallate and resveratrol (EGCG+RES, 282 + 80 mg/d) or placebo supplements for 12 weeks. Fecal microbiota composition (16S rRNA gene amplicon sequencing, V3-V4 region), in vivo whole-body fat oxidation (indirect calorimetry), and mitochondrial respiration in permeabilized skeletal muscle fibers (SkM-Ox; ex vivo respirometry) were determined pre- and post-intervention. Overall, EGCG+RES supplementation did not affect gut microbiota composition. Akkermansia, Ruminococcaceae UCG-002, Subdoligranulum, and Lachnospiraceae UCG-004 were more abundant, while Veillonella, Tyzzerella 4, Clostridium innocuum group, Ruminococcus gnavus group, Escherichia-Shigella, and an uncultured Ruminococcaceae family genus were less abundant in women compared to men. In women, only baseline Eubacterium ventriosum group abundance correlated with EGCG+RES-induced changes in SkM-Ox. In men, low Dorea, Barnsiella, Anaerotruncus, Ruminococcus, Subdoligranulum, Coprococcus, Eubacterium ventriosum group, Ruminococcaceae UCG-003, and a Ruminococcaceae family genus abundance, and high Blautia abundance at baseline were associated with improvements in SkM-Ox. Changes in whole-body fat oxidation were not associated with gut microbiota features. We conclude that baseline microbiota composition predicts changes in SkM-Ox as a result of EGCG+RES supplementation in men but not in women. Men may be more prone to diet-induced, gut microbiota-related improvements in cardiometabolic health. These sex-differences should be further investigated in future precision-based intervention studies.
Assuntos
Catequina , Suplementos Nutricionais , Microbioma Gastrointestinal , Obesidade , Sobrepeso , Polifenóis , Resveratrol , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Feminino , Obesidade/microbiologia , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Método Duplo-Cego , Sobrepeso/microbiologia , Sobrepeso/metabolismo , Sobrepeso/tratamento farmacológico , Adulto , Resveratrol/farmacologia , Resveratrol/administração & dosagem , Polifenóis/farmacologia , Polifenóis/metabolismo , Polifenóis/administração & dosagem , Catequina/análogos & derivados , Catequina/farmacologia , Catequina/metabolismo , Catequina/administração & dosagem , Pessoa de Meia-Idade , Fezes/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Bactérias/efeitos dos fármacos , Fatores Sexuais , RNA Ribossômico 16S/genéticaRESUMO
BACKGROUND: Glucagon-like peptide-1 receptor agonist (GLP-1RA) is incretin-based therapy that possessed significant glucose lowering and weight loss properties. The present study aims to analyze the efficacy of GLP-1RA in the management of overweight/obese individuals with prediabetes. METHODS: A thorough search was carried out on the Cochrane Library, ClinicalTrials.gov, Scopus, and Medline databases until April 3rd, 2024, using a mix of pertinent keywords. This review incorporates randomized clinical trials (RCTs) concerning the efficacy of GLP-1RA for prediabetes. The primary outcome was regression to normoglycemia and/or progression to type 2 diabetes (T2D). We used random-effect models to examine the odds ratio (OR) and mean difference (MD). RESULTS: A total of eight RCTs were incorporated. The results of our meta-analysis indicated that GLP-1RA therapy was associated with higher odds of regression to normoglycemia (OR 4.80; 95%CI: 3.40-6.77, p < 0.00001, I2 = 67 %) and lower risk of progression into T2D (OR 0.27; 95%CI: 0.18-0.42, p < 0.00001, I2 = 0 %) in overweight/obese individuals with prediabetes. Administration of GLP-1RA was also associated with higher reduction in HbA1c (MD -0.28 %; p < 0.00001), fasting glucose (MD -0.45 mmol/L; p < 0.00001), and BMI (MD -1.71 kg/m2; p < 0.00001) in comparison to placebo. However, the administration of GLP-1RA was associated with higher incidence of total adverse events (TAEs), treatment discontinuation due to AEs, hypoglycemia, and gastrointestinal AEs. CONCLUSIONS: This study indicates that while GLP-1RA is a potent therapeutic agent for prediabetes, its adverse effects are concerning, thereby precluding its recommendation as a prediabetes therapy.
Assuntos
Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hipoglicemiantes , Obesidade , Sobrepeso , Estado Pré-Diabético , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Estado Pré-Diabético/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Obesidade/tratamento farmacológico , Obesidade/complicações , Sobrepeso/tratamento farmacológico , Sobrepeso/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , PrognósticoRESUMO
AIM: To synthesize the evidence on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in adolescents with overweight or obesity. MATERIALS AND METHODS: For this systematic review and network meta-analysis, we searched five databases and registries until 2 March 2024 for eligible randomized controlled trials (RCTs). The primary outcome was weight change. We did a pairwise meta-analysis to compare GLP-1RAs and placebo, followed by a drug-wise network meta-analysis (NMA) to compare GLP-1RAs against each other. RESULTS: We screened 770 records to include 12 RCTs with 883 participants. The evidence suggests that GLP-1RAs reduced weight (mean difference -4.21 kg, 95% confidence interval [CI] -7.08 to -1.35) and body mass index (BMI; mean difference -2.11 kg/m2, 95% CI -3.60 to -0.62). The evidence on waist circumference, body fat percentage and adverse events (AEs) was very uncertain. The results remained consistent with subgroup analyses for coexisting type 2 diabetes. Longer therapy duration led to a greater reduction in weight and BMI. In the NMA, semaglutide led to the greatest weight reduction, followed by exenatide, liraglutide and lixisenatide. CONCLUSIONS: The evidence suggests that GLP-1RAs reduce most weight-related outcomes in adolescents, with semaglutide being the most efficacious. There is uncertain evidence on body fat and serious AEs, probably due to fewer studies and low incidence, respectively. Larger RCTs with head-to-head comparisons, pragmatic design, adiposity-related outcomes, and economic evaluation can further guide the use and choice of GLP-1RAs.
Assuntos
Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hipoglicemiantes , Metanálise em Rede , Obesidade Infantil , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Adolescente , Hipoglicemiantes/uso terapêutico , Obesidade Infantil/tratamento farmacológico , Obesidade Infantil/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Exenatida/uso terapêutico , Sobrepeso/complicações , Sobrepeso/tratamento farmacológico , Liraglutida/uso terapêutico , Feminino , Redução de Peso/efeitos dos fármacos , Masculino , Comorbidade , Agonistas do Receptor do Peptídeo 1 Semelhante ao GlucagonAssuntos
Diabetes Mellitus Tipo 2 , Jejum , Hipoglicemiantes , Sobrepeso , Humanos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/etiologia , Hipoglicemiantes/uso terapêutico , Refeições , Metformina/uso terapêutico , Hemoglobinas Glicadas/análise , Sobrepeso/sangue , Sobrepeso/complicações , Sobrepeso/dietoterapia , Sobrepeso/tratamento farmacológico , Alimentos EspecializadosRESUMO
Importance: Although tirzepatide and semaglutide were shown to reduce weight in randomized clinical trials, data from head-to-head comparisons in populations with overweight or obesity are not yet available. Objective: To compare on-treatment weight loss and rates of gastrointestinal adverse events (AEs) among adults with overweight or obesity receiving tirzepatide or semaglutide labeled for type 2 diabetes (T2D) in a clinical setting. Design, Setting, and Participants: In this cohort study, adults with overweight or obesity receiving semaglutide or tirzepatide between May 2022 and September 2023 were identified using electronic health record (EHR) data linked to dispensing information from a collective of US health care systems. On-treatment weight outcomes through November 3, 2023, were assessed. Adults with overweight or obesity and regular care in the year before initiation, no prior glucagon-like peptide 1 receptor agonist receptor agonist use, a prescription within 60 days prior to initiation, and an available baseline weight were identified. The analysis was completed on April 3, 2024. Exposures: Tirzepatide or semaglutide in formulations labeled for T2D, on or off label. Main Outcomes and Measures: On-treatment weight change in a propensity score-matched population, assessed as hazard of achieving 5% or greater, 10% or greater, and 15% or greater weight loss, and percentage change in weight at 3, 6, and 12 months. Hazards of gastrointestinal AEs were compared. Results: Among 41â¯222 adults meeting the study criteria (semaglutide, 32â¯029; tirzepatide, 9193), 18â¯386 remained after propensity score matching. The mean (SD) age was 52.0 (12.9) years, 12â¯970 were female (70.5%), 14â¯182 were white (77.1%), 2171 Black (11.8%), 354 Asian (1.9%), 1679 were of other or unknown race, and 9563 (52.0%) had T2D. The mean (SD) baseline weight was 110 (25.8) kg. Follow-up was ended by discontinuation for 5140 patients (55.9%) receiving tirzepatide and 4823 (52.5%) receiving semaglutide. Patients receiving tirzepatide were significantly more likely to achieve weight loss (≥5%; hazard ratio [HR], 1.76, 95% CI, 1.68, 1.84; ≥10%; HR, 2.54; 95% CI, 2.37, 2.73; and ≥15%; HR, 3.24; 95% CI, 2.91, 3.61). On-treatment changes in weight were larger for patients receiving tirzepatide at 3 months (difference, -2.4%; 95% CI -2.5% to -2.2%), 6 months (difference, -4.3%; 95% CI, -4.7% to -4.0%), and 12 months (difference, -6.9%; 95% CI, -7.9% to -5.8%). Rates of gastrointestinal AEs were similar between groups. Conclusions and Relevance: In this population of adults with overweight or obesity, use of tirzepatide was associated with significantly greater weight loss than semaglutide. Future study is needed to understand differences in other important outcomes.
Assuntos
Peptídeos Semelhantes ao Glucagon , Obesidade , Sobrepeso , Redução de Peso , Humanos , Masculino , Feminino , Redução de Peso/efeitos dos fármacos , Pessoa de Meia-Idade , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Adulto , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Idoso , Receptor do Peptídeo Semelhante ao Glucagon 2 , Polipeptídeo Inibidor GástricoRESUMO
White kidney bean (Phaseolus vulgaris L.) extracts can aid weight management by reducing calorie intake from complex carbohydrates through alpha-amylase inhibition. We examined the impact of a proprietary aqueous extract from whole dried white kidney beans standardized by its alpha-amylase inhibitor activity (Phase 2 white kidney bean extract (WKBE)) on weight management in subjects with overweight and moderate obesity. In a randomized, double-blind, placebo-controlled fashion, 81 participants completed the study and ingested either a high dose of Phase 2 (1000 mg, WKBE HIGH), a low dose (700 mg, WKBE LOW), or a matching placebo (microcrystalline cellulose, PLA) three times a day, 30 min before meals, for 12 weeks during a calorie restricted diet. In a dose-dependent manner, Phase 2 significantly reduced body weight, fat mass, BMI, waist, hip and in the WKBE HIGH group thigh circumference. Phase 2 is an effective and safe supplement aiding weight and fat loss. ClinicalTrials.gov identifier NCT02930668.
Assuntos
Phaseolus , Extratos Vegetais , Humanos , Masculino , Feminino , Método Duplo-Cego , Phaseolus/química , Pessoa de Meia-Idade , Adulto , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Redução de Peso/efeitos dos fármacos , Obesidade/tratamento farmacológico , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo , Sobrepeso/tratamento farmacológico , Lectinas de PlantasRESUMO
Semaglutide is found to be efficient for weight loss in patients with overweight or obesity with diabetes mellitus (DM). With a wide range of adverse events reported, the efficacy and safety of once-weekly subcutaneous semaglutide in individuals without DM, with overweight or obesity, is unclear. We conducted a comprehensive meta-analysis of randomized studies on once-weekly semaglutide in this patient population. We identified nine studies with 11,641 patients in the semaglutide group and 10,479 in the placebo group. We observed that semaglutide resulted in significant benefits, including change in body weight (%): mean difference (MD) of -11.49% (p < 0.0001), change in absolute body weight: MD of -11.74 kg (p < 0.0001), and change in waist circumference: MD of -9.06 cm (p < 0.0001). Gastrointestinal side effects are predominant including nausea: odds ratio (OR) of 4.06 (p < 0.0001), vomiting: OR of 4.43 (p < 0.0001), diarrhea: OR of 2.10 (p < 0.0001), constipation: OR of 2.43 (p < 0.0001), gallbladder disorders: OR of 1.26 (p = 0.010), and cholelithiasis: OR of 2.06 (p = 0.04). Serious adverse events were not statistically significant: OR of 1.06 (p = 0.82). However, the percentage of participants discontinuing due to adverse events and gastrointestinal side effects was statistically significant: ORs of 2.22 (p < 0.0001) and 3.77 (p < 0.0001), respectively. This study shows that in patients with overweight or obesity without DM, once-weekly subcutaneous semaglutide can significantly decrease body weight without risk of serious adverse events when compared with a placebo. However, gastrointestinal side effects are predominant with semaglutide, which can result in medication discontinuation.
Assuntos
Peptídeos Semelhantes ao Glucagon , Obesidade , Sobrepeso , Ensaios Clínicos Controlados Aleatórios como Assunto , Redução de Peso , Humanos , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Redução de Peso/efeitos dos fármacos , Obesidade/tratamento farmacológico , Obesidade/complicações , Injeções Subcutâneas , Sobrepeso/complicações , Sobrepeso/tratamento farmacológico , Resultado do Tratamento , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/administração & dosagem , Fármacos Antiobesidade/uso terapêutico , Esquema de MedicaçãoRESUMO
Objective: The aim of this meta-analysis was to investigate the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on blood glucose and weight in adolescents with overweight/obesity and/or type 2 diabetes mellitus (T2DM) aged <18 years. Methods: PubMed, Embase, Web of Science, and Cochrane Library were searched for all randomized controlled trials (RCTs) up to August 2023 comparing GLP-1RAs with placebo in overweight/obese and/or T2DM adolescents and extracted relevant data for meta-analysis. Results: Fourteen RCTs were included in the meta-analysis with a total of 1,262 participants. Results revealed that the GLP-1RAs group had a more significant reduction in glycosylated hemoglobin A1c (HbA1c; risk difference (RD)=-0.34%, p<0.001) than the control group. However, there was no difference in fasting plasma glucose [fasting plasma glucose (FPG); RD=-2.07 mg/dL, p=0.065] between the two groups. Nonetheless, the experimental group that received exenatide showed no significant reduction in HbA1c (p=0.253) and FPG (p=0.611) between the two groups. The GLP-1RAs group had a more significant decline in body weight (RD=-4.28 kg, p=0.002) and body mass index (BMI) (RD=-1.63 kg/m2, p=0.002) compared to the control group. The experimental group was given liraglutide (RD=-2.31 kg, p=0.038) or exenatide (RD=-2.70 kg, p<0.001). Compared to the control group, the experimental group had a more significant drop in body weight than the control group. However, for the experimental group that received liraglutide, the BMI had a no significant reduction between the two groups (RD=-0.81 kg/m2, p=0.260). For the experimental group using exenatide, BMI declined more significantly in the intervention group than in the control group (RD=-1.14 kg/m2, p<0.001). Conclusion: This study showed that GLP-1RAs reduced HbA1c, FPG, and weight loss in overweight/obese and/or T2DM adolescents. Liraglutide was better than exenatide in terms of glucose reduction. Nevertheless, in terms of weight control, exenatide was more effective than liraglutide.
Assuntos
Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hipoglicemiantes , Sobrepeso , Obesidade Infantil , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Adolescente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Sobrepeso/tratamento farmacológico , Obesidade Infantil/tratamento farmacológico , Glicemia/efeitos dos fármacos , Exenatida/uso terapêutico , Exenatida/administração & dosagem , Hemoglobinas Glicadas/efeitos dos fármacos , Hemoglobinas Glicadas/metabolismo , Liraglutida/uso terapêutico , Resultado do Tratamento , Obesidade/tratamento farmacológico , Agonistas do Receptor do Peptídeo 1 Semelhante ao GlucagonRESUMO
BACKGROUND: Moxonidine, an imidazoline I1 receptor agonist, is an effective antihypertensive drug that was shown to improve insulin sensitivity. RAAS-blockers are recommended as first-line therapy in patients with diabetes, alone or in combination with a calcium-channel antagonist or a diuretic. AIMS: This study compared the effects of moxonidine and ramipril on blood pressure (BP) and glucose metabolism in overweight patients with mild-to-moderate hypertension and impaired fasting glucose or type 2 diabetes. METHODS: Treatment-naïve patients for hypertension and dysglycemia were randomized to 12 weeks of double-blind moxonidine 0.4 mg or ramipril 5 mg once-daily treatment. At 12 weeks, for a further 12 weeks non-responders received combination of mox/ram, while responders continued blinded treatment. RESULTS: Moxonidine and ramipril were equivalent in lowering SiDBP and SiSBP at the end of the first 12 weeks. The responder rate was approximately 50% in both groups, with a mean SiDBP and SiSBP decrease of 10 and 15 mm Hg in the responders, respectively. The normalization rate (SiDBP < 85 mm Hg) was non significantly different between treatments groups. Moxonidine reduced heart rate (HR) (average -3.5 bpm, p = 0.017) during monotherapy, and when added to ramipril. HbA1c decreased significantly at Week 12 in both groups. Neither drug affected glucose or insulin response to the oral glucose tolerance test. In non-responders, moxonidine/ramipril combination further reduced BP without compromising metabolic parameters. CONCLUSION: Moxonidine 0.4 mg and ramipril 5 mg were equally effective on BP lowering and were well tolerated and mostly metabolically neutral either as monotherapies or in combination. HR was lowered on moxonidine treatment.
Assuntos
Anti-Hipertensivos , Glicemia , Pressão Sanguínea , Diabetes Mellitus Tipo 2 , Quimioterapia Combinada , Frequência Cardíaca , Hipertensão , Imidazóis , Sobrepeso , Ramipril , Humanos , Ramipril/administração & dosagem , Ramipril/uso terapêutico , Ramipril/farmacologia , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Feminino , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Método Duplo-Cego , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Imidazóis/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/efeitos adversos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Sobrepeso/tratamento farmacológico , Sobrepeso/fisiopatologia , Sobrepeso/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Idoso , Adulto , Resultado do Tratamento , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/efeitos adversosRESUMO
OBJECTIVE: To determine whether semaglutide slows progression of glycemia in people with cardiovascular disease and overweight or obesity but without diabetes. RESEARCH DESIGN AND METHODS: In a multicenter, double-blind trial, participants aged ≥45 years, with BMI ≥27 kg/m2, and with preexisting cardiovascular disease but without diabetes (HbA1c <6.5%) were randomized to receive subcutaneous semaglutide (2.4 mg weekly) or placebo. Major glycemic outcomes were HbA1c and proportions achieving biochemical normoglycemia (HbA1c <5.7%) and progressing to biochemical diabetes (HbA1c ≥6.5%). RESULTS: Of 17,604 participants, 8,803 were assigned to semaglutide and 8,801 to placebo. Mean ± SD intervention exposure was 152 ± 56 weeks and follow-up 176 ± 40 weeks. In both treatment arms mean nadir HbA1c for participants was at 20 weeks. Thereafter, HbA1c increased similarly in both arms, with a mean difference of -0.32 percentage points (95% CI -0.33 to -0.30; -3.49 mmol/mol [-3.66 to -3.32]) and with the difference favoring semaglutide throughout the study (P < 0.0001). Body weight plateaued at 65 weeks and was 8.9% lower with semaglutide. At week 156, a greater proportion treated with semaglutide were normoglycemic (69.5% vs. 35.8%; P < 0.0001) and a smaller proportion had biochemical diabetes by week 156 (1.5% vs. 6.9%; P < 0.0001). The number needed to treat was 18.5 to prevent a case of diabetes. Both regression and progression were dependent on glycemia at baseline, with the magnitude of weight reduction important in mediating 24.5% of progression and 27.1% of regression. CONCLUSIONS: In people with preexisting cardiovascular disease and overweight or obesity but without diabetes, long-term semaglutide increases regression to biochemical normoglycemia and reduces progression to biochemical diabetes but does not slow glycemic progression over time.
Assuntos
Glicemia , Peptídeos Semelhantes ao Glucagon , Hemoglobinas Glicadas , Obesidade , Sobrepeso , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Sobrepeso/tratamento farmacológico , Sobrepeso/complicações , Obesidade/tratamento farmacológico , Obesidade/complicações , Idoso , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Método Duplo-Cego , Hemoglobinas Glicadas/metabolismo , Hipoglicemiantes/uso terapêuticoRESUMO
OBJECTIVE: To evaluate the cardiovascular effects of semaglutide by baseline glycated hemoglobin (HbA1c) and change in HbA1c in a prespecified analysis of Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT). RESEARCH DESIGN AND METHODS: In SELECT, people with overweight or obesity and atherosclerotic cardiovascular disease without diabetes were randomized to weekly semaglutide 2.4 mg or placebo. The primary end point of first major adverse cardiovascular event (MACE) (cardiovascular mortality, nonfatal myocardial infarction, or stroke) was reduced by 20% with semaglutide versus placebo. Analysis of outcomes included first MACE, its individual components, expanded MACE (cardiovascular mortality, nonfatal myocardial infarction, or stroke; coronary revascularization; or hospitalization for unstable angina), a heart failure composite (heart failure hospitalization or urgent medical visit or cardiovascular mortality), coronary revascularization, and all-cause mortality by baseline HbA1c subgroup and categories of HbA1c change (<-0.3, -0.3 to 0.3, and >0.3 percentage points) from baseline to 20 weeks using the intention-to-treat principle with Cox proportional hazards. RESULTS: Among 17,604 participants (mean age 61.6 years, 72.3% male), baseline HbA1c was <5.7% for 33.5%, 5.7% to <6.0% for 34.6%, and 6.0% to <6.5% for 31.9%. Cardiovascular risk reduction with semaglutide versus placebo was not shown to be different across baseline HbA1c groups and was consistent with that of the overall study for all end points, except all-cause mortality. Cardiovascular outcomes were also consistent across subgroups of HbA1c change. CONCLUSIONS: In people with overweight or obesity and established atherosclerotic cardiovascular disease but not diabetes, semaglutide reduced cardiovascular events irrespective of baseline HbA1c or change in HbA1c. Thus, semaglutide is expected to confer cardiovascular benefits in people with established atherosclerotic cardiovascular disease who are normoglycemic at baseline and/or in those without HbA1c improvements.
Assuntos
Peptídeos Semelhantes ao Glucagon , Hemoglobinas Glicadas , Obesidade , Sobrepeso , Humanos , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Hemoglobinas Glicadas/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Obesidade/complicações , Obesidade/tratamento farmacológico , Sobrepeso/complicações , Sobrepeso/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/mortalidade , Hipoglicemiantes/uso terapêuticoRESUMO
Pomegranate juice (PJ) and inulin have been reported to ameliorate diet-induced metabolic disorders by regulating gut microbiota dysbiosis. However, there was a lack of clinical evidence for the combined effects of PJ and inulin on regulating gut microbiota in individuals with metabolic disorders. A double-blind, parallel, randomized, placebo-controlled trial was conducted, and 68 overweight/obese individuals (25 ≤ BMI ≤ 35 kg/m2) were randomly assigned to receive 200 mL/d PJ, PJ supplemented with inulin, or placebo for 3 weeks. Our results showed that PJ and PJ+inulin did not significantly alter the levels of anthropometric and blood biochemical indicators after 3 weeks of treatment. However, there was an increasingly significant impact from placebo to PJ to PJ+inulin on the composition of gut microbiota. Detailed bacterial abundance analysis further showed that PJ+inulin treatment more profoundly resulted in significant changes in the abundance of gut microbiota at each taxonomic level than PJ. Moreover, PJ+inulin treatment also promoted the production of microbiota-associated short-chain fatty acids and pomegranate polyphenol metabolites, which correlated with the abundance of the bacterial genus. Our results suggested that PJ supplemented with inulin modulates gut microbiota composition and thus promotes the production of microbiota-associated metabolites that exert potential beneficial effects in overweight/obese subjects.
Assuntos
Bactérias , Sucos de Frutas e Vegetais , Microbioma Gastrointestinal , Inulina , Obesidade , Sobrepeso , Punica granatum , Humanos , Inulina/farmacologia , Inulina/administração & dosagem , Inulina/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Adulto , Obesidade/metabolismo , Obesidade/microbiologia , Obesidade/dietoterapia , Obesidade/tratamento farmacológico , Punica granatum/química , Punica granatum/metabolismo , Feminino , Pessoa de Meia-Idade , Sobrepeso/metabolismo , Sobrepeso/microbiologia , Sobrepeso/tratamento farmacológico , Sobrepeso/dietoterapia , Método Duplo-Cego , Sucos de Frutas e Vegetais/análise , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Bactérias/isolamento & purificação , Bactérias/efeitos dos fármacos , Suplementos Nutricionais/análise , Ácidos Graxos Voláteis/metabolismo , Adulto JovemRESUMO
AIMS: To summarize the effects of semaglutide 2.4 mg on weight-related quality of life (WRQOL) and health-related quality of life (HRQOL), focusing on the confirmatory secondary endpoint of physical functioning. MATERIALS AND METHODS: The STEP 1-4 Phase 3a, 68-week, double-blind, randomized controlled trials assessed the efficacy and safety of semaglutide 2.4 mg versus placebo in individuals with overweight/obesity. WRQOL and HRQOL were assessed by change from baseline to Week 68 in two different but complementary measures, the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT; STEP 1 and 2) and the SF-36v2 Health Survey Acute (SF-36v2; STEP 1-4). RESULTS: Superiority for semaglutide 2.4 mg over placebo based on IWQOL-Lite-CT and SF-36v2 physical functioning scores was confirmed in STEP 1 and 2 and in STEP 1, 2 and 4, respectively. At Week 68, a greater proportion of participants treated with semaglutide 2.4 mg than with placebo reached meaningful within-person change (MWPC) thresholds for IWQOL-Lite-CT Physical Function scores in STEP 1 (51.8% vs. 28.3%; p < 0.0001) and STEP 2 (39.6% vs. 29.5%; p = 0.0083) and the MWPC threshold for SF-36v2 Physical Functioning in STEP 1 (39.8% vs. 24.1%; p < 0.0001), STEP 2 (41.0% vs. 27.3%; p = 0.0001) and STEP 4 (18.0% vs. 6.6%; p < 0.0001). All other IWQOL-Lite-CT and SF-36v2 scale scores in STEP 1-4 were numerically improved with semaglutide 2.4 mg versus placebo, except for SF-36v2 Role Emotional in STEP 2. CONCLUSIONS: Semaglutide 2.4 mg significantly improved physical functioning, with greater proportions of participants achieving MWPC compared with placebo, and showed beneficial effects on WRQOL and HRQOL beyond physical functioning.