SUN-675 Very Low Energy Ketogenic Therapy In Combination With Liraglutide As A Synergic Strategy For The Treatment Of Obesity: A Real-world Clinical Evaluation

Introducción: El envejecimiento provoca, entre otros cambios, disminución de la masa muscular y reducción de la independencia funcional. La práctica regular de actividad física es considerada una herramienta esencial para lograr un envejecimiento saludable. Objetivo: Analizar los efectos de un programa de entrenamiento multicomponente sobre medidas antropométricas, condición física y calidad de vida relacionada con la salud en personas mayores independientes funcionalmente. Material y Métodos: Estudio pre-experimental (con pre y post evaluación) que contó con 17 personas mayores (13 mujeres y 4 hombres) con una edad media de 72,5 años. Se evaluaron medidas antropométricas básicas (peso corporal, estatura bípeda e índice de masa corporal [IMC]), condición física a través del Senior Fitness Test y la calidad de vida relacionada con la salud por medio de la encuesta SF-36. Se realizaron comparaciones pre y post intervención a través de las pruebas t de Student y Wilcoxon considerando un p<0,05. Resultados: Luego de 12 semanas de intervención las personas mayores reportaron una reducción significativa (p<0,001) del peso corporal e IMC. Aumento significativo (p<0,05) en las pruebas relacionadas con la fuerza del tren inferior y superior, capacidad cardiorrespiratoria, agilidad y equilibrio dinámico, y una reducción significativa (p<0,05) en la distancia entre manos (para la flexibilidad del tren superior) y entre manos y pie (para la flexibilidad del tren inferior). Además, se presentó un aumento significativo (p<0,05) en siete dimensiones de la calidad de vida relacionada con la salud (i.e. función física, rol físico, salud general, vitalidad, función social, rol emocional y salud mental) y una reducción significativa (p=0,000) del dolor corporal. Conclusiones: Existe una reducción significativa del peso corporal e IMC y un aumento significativo de la condición física y calidad de vida relacionada con la salud en personas mayores luego de 12 semanas de participación en un programa de entrenamiento multicomponente.

Semaglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, represents a significant development in the therapeutic landscape for type 2 diabetes mellitus (T2DM). Its molecular structure, featuring 94% homology to human GLP-1 with modifications for albumin binding and resistance to dipeptidyl peptidase-4 (DPP-4) degradation, confers an extended half-life of approximately one week. This profile permits once-weekly subcutaneous or, uniquely, once-daily oral administration facilitated by the absorption enhancer sodium N-(8-[2-hydroxybenzoyl]-amino) caprylate (SNAC). The mechanism of action involves glucose-dependent stimulation of insulin secretion, suppression of inappropriate glucagon release, and delayed gastric emptying. Apart from glycemic control, semaglutide exerts central effects on appetite regulation, leading to significant reductions in body weight. Large-scale clinical trial programs (SUSTAIN for subcutaneous, PIONEER for oral) have shown robust reductions in HbA1c and body weight compared to placebo and active comparators, including other GLP-1 receptor agonists and SGLT2 inhibitors. Moreover, dedicated cardiovascular outcome trials have established its benefit in reducing major adverse cardiovascular events (MACE) in patients with T2DM and high cardiovascular risk. Its clinical utility extends to chronic weight management, with higher-dose formulations approved for obesity. The primary adverse events are gastrointestinal in nature, including nausea, vomiting, and diarrhea, which are typically dose-dependent and transient. Therapeutic monitoring include potential risks for diabetic retinopathy complications and the class-specific boxed warning regarding thyroid C-cell tumors, derived from rodent studies

The effects of capsinoids supplementation on body composition and anthropometric measures: A systematic review and dose–response meta-analysis of randomized controlled trials

Disclosure: A.L. Peters: Advisory Board Member; Self; Abbott Diabetes Care, Eli Lilly & Company, Medscape, Novo Nordisk, Zealand. Grant Recipient; Self; Dexcom, Insulet Corporation. Stock Owner; Self; Omada Health, Teladoc. Other; Self; Abbott Diabetes Care. R. Buzzetti: Consulting Fee; Self; Sanofi, Novo Nordisk, Eli Lilly & Company. Speaker; Self; AstraZeneca, Abbott Laboratories. C.J. Lee: Employee; Self; Eli Lilly & Company. Stock Owner; Self; Eli Lilly & Company. I. Pavo: Employee; Self; Eli Lilly & Company. Stock Owner; Self; Eli Lilly & Company. M. Liu: Other; Self; Eli Lilly & Company. J.S. Paik: Employee; Self; Eli Lilly & Company. Stock Owner; Self; Eli Lilly & Company. Tirzepatide, a novel once weekly GIP and GLP-1 receptor agonist, is approved for treatment of type 2 diabetes (T2D). People with T2D and positive glutamic acid decarboxylase autoantibodies (GADA), which is also referred to as latent autoimmune diabetes in adults (LADA), may often remain undetected and may be associated with more rapid progression to insulin therapy. The diagnosis is primarily made by the presence of GADA in patients previously diagnosed with T2D. The aim of this post hoc analysis was to evaluate the effect of tirzepatide on hemoglobin A1c (HbA1c) levels in people with T2D who were GADA-positive versus GADA-negative from the Phase 3 SURPASS clinical trial program. Tirzepatide-treated patients from SURPASS 2-5 studies were included in this analysis. Patients who had GADA concentrations ≥5 IU/mL were categorized as GADA-positive (ELISA, RSR Ltd., Cardiff, UK). Change from baseline in HbA1c at 40/42 weeks was assessed in GADA-positive vs GADA-negative patients using mixed model repeated measures from the efficacy analysis set, adjusting for baseline covariates including study, sex, HbA1c, and body mass index (BMI). All randomized patients who took at least one dose of study drug, excluding patients who discontinued study drug due to inadvertent enrollment and excluding data after initiation of rescue medication or premature discontinuation of study drug, were included in this analysis. Of the 3827 tirzepatide-treated patients who were tested for GADA, 3671 (95.9%) were GADA-negative, 120 (3.2%) were GADA-positive, and 36 (0.9%) were “no GADA status”. Baseline parameters were similar between the groups, except for baseline BMI and serum triglyceride concentration which were slightly lower in GADA-positive patients compared to GADA-negative patients (mean baseline BMI [SD] 32.2 [6.1] vs 33.6 [6.3] kg/m2, mean triglycerides 169.2 [101.3] vs 188.1 [131.4] mg/dL). At 40/42 weeks, both groups achieved significant reductions in HbA1c (-2.11% vs -2.32%; p<0.001 for both groups) and body weight (-9.2 kg vs -9.6 kg; p<0.001 for both groups), for GADA-positive vs. GADA-negative patients, respectively. Reductions in HbA1c were slightly greater in GADA-negative patients (estimated treatment differences [95% confidence interval]: 0.21% [0.03, 0.39]; p=0.024), whereas reductions in body weight did not significantly differ between groups (0.38 kg [-0.99, 1.75]; p=0.588). These data demonstrate that tirzepatide was effective in reducing HbA1c and body weight, irrespective of GADA status in adults with T2D, thus suggesting that tirzepatide may be effective to improve glycemic control in GADA-positive individuals. Future studies could help elucidate the long-term impact of GADA positivity on the progression of diabetes. Presentation: Thursday, June 15, 2023

Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are a class of antidiabetic drugs developed over the past 15 years. GLP-1, a gastrointestinal peptide hormone that contributes to the postprandial “incretin effect”, stimulates glucose-dependent insulin secretion. The incretin effect is greatly diminished in type 2 diabetes, but can be restored by GLP-1RAs. These drugs also exert other GLP-1 effects, including reducing glucagon secretion, delaying gastric emptying, reducing food intake, improving cardiac ventricular function, and lowering blood pressure. Short-acting GLP-1RAs are administered once daily (lixisenatide) or twice daily (exenatide); long-acting GLP 1RAs are administered once daily (liraglutide) or once weekly (slow-release exenatide, dulaglutide, albiglutide). All GLP-1RAs significantly reduce glycated hemoglobin (HbA1c) in patients with type 2 diabetes whose glycemic control is inadequate with oral antidiabetic drugs. Compared with other antidiabetic medications, GLP-1RAs provide better glycemic control with the additional benefit of weight loss. Within this class, long-acting GLP-1RAs are more efficacious than short-acting GLP-1RAs, with similar or lower risk of hypoglycemia and lower incidence of gastrointestinal adverse effects. Head-to-head trials and a network meta-analysis suggest that once daily liraglutide is the most effective GLP-1RA in reducing HbA1c. Dulaglutide is the only once-weekly GLP 1RA demonstrated to be noninferior to liraglutide. The once-weekly GLP-1RAs offer additional advantages to patients, including fewer injections and easy-to-use, single-dose pen devices. Despite the relatively recent development of GLP-1RAs, international diabetes guidelines recognize the benefits of this class of drugs and recommend them as a treatment option for patients with type 2 diabetes.

Delirium occurs in up to 30% of hospitalised patients and is associated with prolonged hospital stay and increased morbidity and mortality. Recently published reports have suggested that the standard drug for delirium, haloperidol, a typical antipsychotic that may cause adverse extrapyramidal symptoms among patients, may be replaced by atypical antipsychotics such as risperidone, olanzapine or quetiapine, that are as effective as haloperidol in controlling delirium, but that have a lower incidence of extrapyramidal adverse effects. To compare the efficacy and incidence of adverse effects of haloperidol with risperidone, olanzapine, and quetiapine in the treatment of delirium. The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 7 August 2006 using the search terms:haloperidol or haldol or risperidone or risperdal* or quetiapine or seroquel* or olanzapine or zyprexa* or aminotriazole or sertindole or leponex* or zeldox* or ziprasidone. Types of studies included unconfounded, randomised trials with concealed allocation of subjects. For inclusion trials had to have assessed patients pre- and post-treatment. Where cross-over studies are included, only data from the first part of the study were examined. Interrupted time series were excluded. Length of trial and number of measurements did not influence the selection of trials for study. Where indicated, individual patient data were requested for further examination. Two reviewers extracted data from included trials. Data were pooled where possible, and analysed using appropriate statistical methods. Odds ratios of average differences were calculated. Only 'intention to treat' data were included. Analysis included haloperidol treated patients, compared with placebo. Three studies were found that satisfied selection criteria. These studies compared haloperidol with risperidone, olanzapine, and placebo in the management of delirium and in the incidence of adverse drug reactions. Decrease in delirium scores were not significantly different comparing the effect of low dose haloperidol (< 3.0 mg per day) with the atypical antipsychotics olanzapine and risperidone (Odds ratio 0.63 (95% CI 10.29 - 1.38; p = 0.25). Low dose haloperidol did not have a higher incidence of adverse effects than the atypical antipsychotics. High dose haloperidol (> 4.5 mg per day) in one study was associated with an increased incidence of extrapyramidal adverse effects, compared with olanzapine. Low dose haloperidol decreased the severity and duration of delirium in post-operative patients, although not the incidence of delirium, compared to placebo controls in one study. There were no controlled trials comparing quetiapine with haloperidol. There is no evidence that haloperidol in low dosage has different efficacy in comparison with the atypical antipsychotics olanzapine and risperidone in the management of delirium or has a greater frequency of adverse drug effects than these drugs. High dose haloperidol was associated with a greater incidence of side effects, mainly parkinsonism, than the atypical antipsychotics. Low dose haloperidol may be effective in decreasing the degree and duration of delirium in post-operative patients, compared with placebo. These conclusions must be tempered by the observation that they are based on small studies of limited scope, and therefore will require further corroborating evidence before they can be translated into specific recommendation for the treatment of delirium.

Background and objectivesA plant-based diet is an effective strategy in the treatment of obesity. In this 16-week randomized clinical trial, we tested the effect of a plant-based diet on body composition and insulin resistance. As a part of this trial, we investigated the role of plant protein on these outcomes.Subjects and methodsOverweight participants (n = 75) were randomized to follow a plant-based (n = 38) or a control diet (n = 37). Dual X-ray Absorptiometry assessed body composition, Homeostasis Model Assessment (HOMA-IR) assessed insulin resistance, and a linear regression model was used to test the relationship between protein intake, body composition, and insulin resistance.ResultsThe plant-based vegan diet proved to be superior to the control diet in improving body weight, fat mass, and insulin resistance markers. Only the vegan group showed significant reductions in body weight (treatment effect −6.5 [95% CI −8.9 to −4.1] kg; Gxt, p < 0.001), fat mass (treatment effect −4.3 [95% CI −5.4 to −3.2] kg; Gxt, p < 0.001), and HOMA-IR (treatment effect −1.0 [95% CI −1.2 to −0.8]; Gxt, p = 0.004). The decrease in fat mass was associated with an increased intake of plant protein and decreased intake of animal protein (r = -0.30, p = 0.011; and r = +0.39, p = 0.001, respectively). In particular, decreased % leucine intake was associated with a decrease in fat mass (r = +0.40; p < 0.001), in both unadjusted and adjusted models for changes in BMI and energy intake. In addition, decreased % histidine intake was associated with a decrease in insulin resistance (r = +0.38; p = 0.003), also independent of changes in BMI and energy intake.ConclusionsThese findings provide evidence that plant protein, as a part of a plant-based diet, and the resulting limitation of leucine and histidine intake are associated with improvements in body composition and reductions in both body weight and insulin resistance.

Tirzepatide is a novel dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors that offers promising therapeutic potential beyond glycemic control. Originally developed for the treatment of type 2 diabetes mellitus, tirzepatide has demonstrated a wide array of pleiotropic effects in clinical studies. These include significant reductions in body weight, improvements in lipid profiles, decreased blood pressure, and attenuation of hepatic steatosis. Emerging data also support its cardioprotective and nephroprotective roles, as well as efficacy in patients with heart failure with preserved ejection fraction (HFpEF). Furthermore, tirzepatide is currently under investigation for the treatment of obstructive sleep apnea and shows early promise in neuroprotection. This review summarizes the current evidence on the diverse biological actions of tirzepatide and discusses their potential clinical implications in the context of metabolic syndrome and associated comorbidities. Materials and methods: A review of the literature available in the PubMed database was performed, using the key words: “tirzepatide”, “obesity treatment”, “GIP”, “GLP-1”, “glucose-dependent insulinotropic polypeptide”, “glucagon-like peptide-1”. Conclusion: The clinical benefits of tirzepatide extend well beyond glucose lowering, encompassing a broad spectrum of metabolic, cardiovascular and renal effects. These pleiotropic actions position tirzepatide as a valuable pharmacological agent in the multifactorial management of type 2 diabetes, obesity and related conditions. Continued investigation into its mechanisms of action and therapeutic scope may further redefine its role in the treatment of complex metabolic disorders. Given the growing body of evidence, tirzepatide represents a paradigm shift toward integrated care for patients with metabolic syndrome and its systemic manifestations.

Long-acting amylin analogue for weight reduction

The present study determined the effect of black soy peptide supplementation on body weight and body fat in overweight/obese subjects. In a double-blind controlled trial, participants (n = 80) were randomized to either soy peptide supplementation (the test group) or to a placebo (the placebo group). Sixty-four people completed the study, and anthropometric parameters, serum inflammatory markers, and leptin and lipid profiles were measured. After 6 weeks, the test group (n = 35) had significant reductions in body weight (p = 0.003) and body mass index (BMI) (p = 0.004), body fat mass (p = 0.038). After 12 weeks, they also had significant reductions in body weight (p < 0.001), BMI (p < 0.001), body fat percentage (p = 0.002), and body fat mass (p = 0.001). However, these significances were not observed in the placebo group (n = 29). In addition, net changes in body weight and body fat mass in the test group were significantly bigger than those in the placebo group after 12 weeks. Leptin levels were significantly reduced in the test groups (p = 0.047), but were not observed in the placebo group (p = 0.323). Interestingly, the subjects with weight reductions ≥1kg in the test group had greater reductions in circulating leptin levels (p = 0.002). Additionally, fasting insulin levels were significantly reduced in the test groups. The conclusion is that black soy peptide supplementation may be beneficial for body weight control in overweight/obese subjects.

We investigated the effect of exergames and aquatic exercises on lung function and weight loss in obese children. Sixty-one obese male primary-school children were randomly allocated to video game, aquatic exercise, and control groups. Lung functions and anthropometric variables were measured before and after the intervention and after one month (follow-up). In the video game group, an Xbox Kinect game was played for 60 min during three sessions a week. The aquatic aerobic exercise was performed three times per week and consisted of a warm-up, main exercises, and a cool down phase. For the video game group, there was a significant reduction in body weight between (i) pre- and (ii) post-intervention and follow-up. In the aquatic exercise group, there was a significant reduction in body weight between pre- and post-intervention and between pre-intervention and follow-up. Both exercise groups improved the waist/hip ratio index compared to the control group. Forced vital capacity was significantly improved in the follow-up of the video game group and the aquatic exercise group compared to the control group. A significant improvement was found in forced expiratory volume in the first second at post-intervention and follow-up in the video game and the aquatic exercise groups. Exergames and aquatic exercises improved weight loss and lung function in obese children.

Do we need another <scp>SGLT2</scp> inhibitor?

Insecticidal potential of Bowman–Birk proteinase inhibitors from red gram ( Cajanus cajan) and black gram ( Vigna mungo) against lepidopteran insect pests

BackgroundThe high co-prevalence of obesity and end-stage osteoarthritis requiring arthroplasty, with the former being a risk factor for complications during arthroplasty, has led to increasing interest in employing preoperative weight loss interventions such as bariatric surgery and diet modification. However, the current evidence is conflicting, and this study aimed to investigate the effect of weight loss intervention before arthroplasty in prospective randomized controlled trials.MethodsFour electronic databases (MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials) were searched for prospective randomized controlled trials that compared weight loss interventions with usual care from inception to October 2023 by following the PRISMA guidelines. The Cochrane risk of bias tool and GRADE framework were used to assess the quality of the studies. Meta-analyses were performed when sufficient data were available from 2 or more studies.ResultsThree randomized controlled trials involving 198 patients were identified. Two studies employed diet modification, and one study utilized bariatric surgery. All three studies reported significant reductions in body weight and body mass index (BMI), and intervention groups had fewer postoperative complications. There was no difference in the length of stay between the intervention group and the control group. Variable patient-reported outcome measures were used by different research groups.ConclusionWeight loss intervention can achieve significant reductions in body weight and body mass index before arthroplasty, with fewer postoperative complications reported. Further studies with different populations could confirm the effect of these interventions among populations with different obesity characteristics.

AimsTo describe the real‐world use and effectiveness of IDegLira, a fixed‐ratio combination of the basal insulin degludec, and the glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) liraglutide.Materials and MethodsThis European, multicentre, retrospective chart review comprised adults (n = 611) with type 2 diabetes, who started IDegLira ≥6 months before data collection. Clinical characteristics were assessed at baseline (defined as the most recent recording during the 6 months before the first IDegLira prescription) and 3, 6, 9 and 12 months (± 45 days for each time point) after commencing IDegLira, where data were available.ResultsBaseline regimens included non‐injectable medications (19%), basal insulin (19%), GLP‐1RA (10%), free combination therapy (insulin/GLP‐1RA, 24%) and multiple daily‐dose insulin injections (MDI, 28%), all ± oral antidiabetic drugs. After 6 months, significant glycated haemoglobin (HbA1c) reductions were observed in patients overall and in all subgroups (−10 mmol/mol [−0.9%] overall; P < .0001), and a significant reduction in mean body weight (−0.7 kg; P < .05) was observed in patients overall and in patients receiving MDI (−2.4 kg; P < .0001). The mean IDegLira dose was 22, 30 and 32 dose steps at initiation, and at 6 and 12 months follow‐up, respectively. In total, only 67 patients reached the maximum 50 dose steps, with most coming from the free combination therapy (n = 31) or MDI (n = 15) baseline regimen groups. Hypoglycaemia rates were reduced by 82% (rate ratio 0.18; P < .0001) in the 6‐month period after vs before IDegLira initiation. Overall, a total of 12 patients experienced 15 events in the 6 months after IDegLira initiation.ConclusionIn real‐world practice, after 6 months and at a moderate dose, IDegLira resulted in substantial reductions in HbA1c and body weight, with a reduced risk of hypoglycaemia.