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In this phase 3b, open-label, randomized, controlled trial involving adults with obesity without type 2 diabetes, tirzepatide was superior to semaglutide in reducing body weight and waist circumference.

Aims/hypothesis We previously reported that obese individuals with the metabolic syndrome (at risk), compared with obese individuals without the metabolic syndrome (healthy obese), have elevated serum AGEs that strongly correlate with insulin resistance, oxidative stress and inflammation. We hypothesised that a diet low in AGEs (L-AGE) would improve components of the metabolic syndrome in obese individuals, confirming high AGEs as a new risk factor for the metabolic syndrome. Methods A randomised 1 year trial was conducted in obese individuals with the metabolic syndrome in two parallel groups: L-AGE diet vs a regular diet, habitually high in AGEs (Reg-AGE). Participants were allocated to each group by randomisation using random permuted blocks. At baseline and at the end of the trial, we obtained anthropometric variables, blood and urine samples, and performed OGTTs and MRI measurements of visceral and subcutaneous abdominal tissue and carotid artery. Only investigators involved in laboratory determinations were blinded to dietary assignment. Effects on insulin resistance (HOMA-IR) were the primary outcome. Results Sixty-one individuals were randomised to a Reg-AGE diet and 77 to an L-AGE diet; the data of 49 and 51, respectively, were analysed at the study end in 2014. The L-AGE diet markedly improved insulin resistance; modestly decreased body weight; lowered AGEs, oxidative stress and inflammation; and enhanced the protective factors sirtuin 1, AGE receptor 1 and glyoxalase I. The Reg-AGE diet raised AGEs and markers of insulin resistance, oxidative stress and inflammation. There were no effects on MRI-assessed measurements. No side effects from the intervention were identified. HOMA-IR came down from 3.1 ± 1.8 to 1.9 ± 1.3 ( p  < 0.001) in the L-AGE group, while it increased from 2.9 ± 1.2 to 3.6 ± 1.7 ( p  < 0.002) in the Reg-AGE group. Conclusions / interpretation L-AGE ameliorates insulin resistance in obese people with the metabolic syndrome, and may reduce the risk of type 2 diabetes, without necessitating a major reduction in adiposity. Elevated serum AGEs may be used to diagnose and treat ‘at-risk’ obesity. Trial registration ClinicalTrials.gov NCT01363141 Funding The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (DK091231)

Hypertension is becoming a global epidemic for both rural and urban populations; it is a major public health challenge in Iran. Fluoride can be a risk factor for hypertension. Cross-sectional analysis was conducted in two study areas to assess the relation of fluoride with blood pressure prevalence, BMI, waist circumference, and waist-to-hip ratio (WHR) among different age groups in both sexes. The mean value of fluoride concentration in the drinking water from the four study villages varied from 0.68 to 10.30 mg/L. The overall prevalence of HTN and prehypertension in all subjects was 40.7%. The prevalence of isolated systolic hypertension, isolated diastolic hypertension, systolic-diastolic hypertension, and prehypertension in the total sample population was 1.15, 0.28, 9.53, and 29.76%, respectively. The odd ratio of hypertension in residents who drank water with high fluoride levels was higher than that in residents who drank water with lower level of fluoride (OR 2.3, 1.03–5.14). Logistic regression results showed that age (P < 0.001), sex (P = 0.018), BMI (P = 0.015), and the fluoride level in drinking water (P = 0.041) had a significant relationship with increased blood pressure. There were no statistically significant correlations between fluoride and BMI, hip circumference, and waist to hip ratio (WHR). The findings of this study are important for health care personnel and policymakers.

The frequency of obesity has risen dramatically in recent years but only few safe and effective drugs are currently available. We assessed the effect of liraglutide on bodyweight and tolerability in obese individuals without type 2 diabetes. We did a double-blind, placebo-controlled 20-week trial, with open-label orlistat comparator in 19 sites in Europe. 564 individuals (18–65 years of age, body-mass index 30–40 kg/m 2) were randomly assigned, with a telephone or web-based system, to one of four liraglutide doses (1·2 mg, 1·8 mg, 2·4 mg, or 3·0 mg, n=90–95) or to placebo (n=98) administered once a day subcutaneously, or orlistat (120 mg, n=95) three times a day orally. All individuals had a 500 kcal per day energy-deficit diet and increased their physical activity throughout the trial, including the 2-week run-in. Weight change analysed by intention to treat was the primary endpoint. An 84-week open-label extension followed. This study is registered with ClinicalTrials.gov, number NCT00422058. Participants on liraglutide lost significantly more weight than did those on placebo (p=0·003 for liraglutide 1·2 mg and p<0·0001 for liraglutide 1·8–3·0 mg) and orlistat (p=0·003 for liraglutide 2·4 mg and p<0·0001 for liraglutide 3·0 mg). Mean weight loss with liraglutide 1·2–3·0 mg was 4·8 kg, 5·5 kg, 6·3 kg, and 7·2 kg compared with 2·8 kg with placebo and 4·1 kg with orlistat, and was 2·1 kg (95% CI 0·6–3·6) to 4·4 kg (2·9–6·0) greater than that with placebo. More individuals (76%, n=70) lost more than 5% weight with liraglutide 3·0 mg that with placebo (30%, n=29) or orlistat (44%, n=42). Liraglutide reduced blood pressure at all doses, and reduced the prevalence of prediabetes (84–96% reduction) with 1·8–3·0 mg per day. Nausea and vomiting occurred more often in individuals on liraglutide than in those on placebo, but adverse events were mainly transient and rarely led to discontinuation of treatment. Liraglutide treatment over 20 weeks is well tolerated, induces weight loss, improves certain obesity-related risk factors, and reduces prediabetes. Novo Nordisk A/S, Bagsvaerd, Denmark.

Regular consumption of flavonoids may reduce the risk for CVD. However, the effects of individual flavonoids, for example, quercetin, remain unclear. The present study was undertaken to examine the effects of quercetin supplementation on blood pressure, lipid metabolism, markers of oxidative stress, inflammation, and body composition in an at-risk population of ninety-three overweight or obese subjects aged 25–65 years with metabolic syndrome traits. Subjects were randomised to receive 150 mg quercetin/d in a double-blinded, placebo-controlled cross-over trial with 6-week treatment periods separated by a 5-week washout period. Mean fasting plasma quercetin concentrations increased from 71 to 269 nmol/l (P < 0·001) during quercetin treatment. In contrast to placebo, quercetin decreased systolic blood pressure (SBP) by 2·6 mmHg (P < 0·01) in the entire study group, by 2·9 mmHg (P < 0·01) in the subgroup of hypertensive subjects and by 3·7 mmHg (P < 0·001) in the subgroup of younger adults aged 25–50 years. Quercetin decreased serum HDL-cholesterol concentrations (P < 0·001), while total cholesterol, TAG and the LDL:HDL-cholesterol and TAG:HDL-cholesterol ratios were unaltered. Quercetin significantly decreased plasma concentrations of atherogenic oxidised LDL, but did not affect TNF-α and C-reactive protein when compared with placebo. Quercetin supplementation had no effects on nutritional status. Blood parameters of liver and kidney function, haematology and serum electrolytes did not reveal any adverse effects of quercetin. In conclusion, quercetin reduced SBP and plasma oxidised LDL concentrations in overweight subjects with a high-CVD risk phenotype. Our findings provide further evidence that quercetin may provide protection against CVD.

The efficacy of GLP1 receptor agonists (GLP1-RAs) in treating polycystic ovarian syndrome (PCOS) remains unclear. While GLP1-RAs are known to promote weight loss in patients with diabetes and living with obesity, their impact on weight reduction and hormonal regulation in women with PCOS is understudied. Therefore, we aimed to assess the efficacy of GLP1-RAs in PCOS women living with obesity through a meta-analysis, comparing their effects to placebo. The use of GLP1-RAs in PCOS women living with obesity can reduce body mass index and waist circumference as well as improve hyperinsulinism, and hyperandrogenism as well as normalize total testosterone, total cholesterol and HOMA-IR markers in PCOS women living with obesity. We systematically searched the PubMed, Cochrane Central, Scopus and Embase databases to identify randomized controlled trials (RCT) comparing GLP1-RAs versus placebo among women diagnosed with PCOS based on the Rotterdam Criteria. Our primary outcomes of interest included body mass index (BMI), triglycerides, waist circumference, total testosterone, total cholesterol, and HOMA-IR. We performed data extraction and quality assessment for studies that met the inclusion criteria. We pooled mean difference (MD) and 95 % confidence intervals (CI) with a random-effect model for continuous endpoints. We included 176 participants from four RCTs. Semaglutide and Liraglutide were used in 23 (13 %) and 103 (58 %) participants, respectively. GLP1-RAs use was associated with a significant reduction in waist circumference (MD: −5.16 cm; 95 % CI: −6.11 to −4.21; p ˂ 0.00001), body mass index (BMI) (MD: −2.42; 95 % CI: −3.10 to −1.74; p ˂ 0.00001), serum triglycerides (MD: −0.20; 95 % CI: −0.30 to −0.11; p ˂ 0.00001) and total testosterone levels (MD: −1.33; 95 % CI: −2.55 to −0.12; p = 0.03) when compared to placebo. There was no significant difference in total cholesterol (MD: −0.04; 95 % CI: −0.10 to 0.01; p = 0.15) and HOMA-IR (MD: −0.30; 95 % CI: −0.92 to 0.32; p = 0.35) levels. Adverse events information was available for 112 patients, where 49 had light side effects such as nausea and abdominal pain. The use of GLP1-RAs demonstrates efficacy in reducing BMI, triglycerides, waist circumference and total testosterone. There was no significant difference in total cholesterol and HOMA-IR levels. These results signify its viability as a favourable treatment option for managing PCOS symptoms in women living with obesity. •Our findings argue in favor of the use of GLP1-RAs for the treatment of PCOS.•GLP1-RAs reduced BMI, triglycerides, waist circumference, and total testosterone among overweight women with PCOS.•GLP1-RAs should be considered for treating overweight PCOS women who are intolerant to Metformin.

The impact of blood glucose-lowering medications on weight has always been a topic of interest in the treatment of diabetic patients. This study investigates the effect of empagliflozin on weight in patients with prediabetes and type 2 diabetes. This quasi-experimental study was performed on patients with prediabetes or type 2 diabetes with an HbA1c level up to 1% higher than the treatment target, and not using other blood glucose-lowering medications. Patients received 10 milligrams of Empagliflozin once daily for three months, and weight, BMI, waist circumference, and blood pressure were evaluated monthly. Forty-three patients (21 women and 22 men) enrolled. The average weight of patients decreased by 2.96 ± 1.96 kg (3.8%) ( P  < 0.001). BMI decreased by -1.10 ± 0.71 Kg/m 2 (3.72%) ( P  < 0.001). The waist circumference of patients decreased by -3.23 ± 3.69 centimeters ( P  < 0.001). FPG decreased from 114.86 to 109.48 mg/dL ( P  < 0.001), and HbA1c decreased from 6.52% to 6.38% ( P  < 0.001). The weight change was more significant in men than women (-3.59 ± 1.74 vs. -2.30. ± 1.99), ( P  = 0.029). Weight reduction was greater in patients with GFR higher than 90 compared to GFR lower than 90 (-3.34. ± 2.00 vs. -2.16 ± 1.67) ( P  = 0.063). Also, no significant difference was observed in the weight, BMI, and waist circumference changes between different BMI groups (less than 25, 25 to 30, 30 to 35, and higher than 35). The trend of weight and BMI changes during the three-month empagliflozin treatment period was significant ( P  < 0.001) and didn’t reach a plateau level after three months. The change in waist circumference was also significant, reaching a plateau level after one month ( P  < 0.001). There was no significant change in blood pressure. In conclusion the weight, BMI, and waist circumference of patients decreased following the administration of empagliflozin. Weight reduction was more pronounced in males than females and in patients with a GFR above 90 than those with a GFR below 90. Trial registration : This study was approved by the Research Deputy of Kerman University of Medical Sciences with tracking number 401,000,516, IRCT code: IRCT20090317001774N10, and ethical code: IR.KMU.AH.REC.1402.065 was approved by Research Ethics Committee of Afzalipour Hospital- Kerman University of Medical Sciences.

•Eight studies, with 372 participants were included in meta-analysis.•Chia consumption significantly reduced DBP (-7.49 mmHg) and SBP (-5.61 mmHg) in adults.•Chia consumption significantly reduced WC (-1.46 cm) in adults in adults.•Chia consumption did not significantly change the BMI and weight in adults. Growing evidence has suggested that the consumption of chia seed can decrease blood pressure and obesity in adults. However, even studies have reported uncertain findings. The current meta-analysis aimed to assess the findings of randomized controlled trials (RCTs) on the efficacy of chia seed supplementation on blood pressure (systolic blood pressure [SBP], diastolic blood pressure [DBP]) and body composition (waist circumference [WC], weight, body mass index [BMI]) in adults. A systematic search of the literature was carried out in the PubMed, Web of Knowledge, Scopus, Cochrane Central Library, and EMBASE from inception up to October 2024. Data were extracted and analyzed using a random-effects model, and reported as weighted mean differences (WMD) with 95% confidence intervals (CI). A total of eight RCTs involving 372 participants were included in the meta-analysis. The results showed that chia consumption significantly reduced DBP (WMD: -7.49 mmHg; 95% CI: -9.64, -5.34; P < 0.001) and SBP (WMD: -5.61 mmHg; 95% CI: -8.77, -2.44; P = 0.001). Moreover, consuming chia seeds was linked to a notable decrease in WC (WMD: -1.46 cm; 95% CI: -2.68, -0.25; P = 0.01), but it had no significant effect on, BMI (WMD: -0.31 kg/m2; 95% CI: - 0.96, 0.34; P = 0.34) and weight (WMD: 0.09 kg; 95% CI: -0.76, 0.93; P = 0.84). Chia consumption can significantly reduce SBP, DBP, and WC in adults, but no significant impact was showed on BMI and weight. To verify these results, more studies involving a greater number of participants are required.

The current state of knowledge regarding the association of dairy products and weight gain, overweight, and obesity is based on studies reporting contradicting and inconclusive results. The aim of the present study was thus to clarify the link between dairy consumption in relation to changes in anthropometric measures/adiposity by a meta-analytical approach. For the meta-analysis PubMed, EMBASE, Web of Sciences, and google scholar were searched by two independent authors up to May 2016 with no restriction to language or calendar date. Prospective cohort studies reporting about intake of dairy consumption (including milk, yogurt, cheese, butter) and changes in body weight or waist circumference, risk of overweight, obesity, or weight gain were eligible. Pooled effects were calculated using a random effects model, and also a fixed effect model for sensitivity analysis. Due to the heterogeneity of statistical analytical approaches of the studies the analysis were done separately for beta-coefficients of changes in body weight and/or waist circumference per serving of dairy, for differences in weight gain/gain in waist circumference when comparing extreme categories of dairy consumption, and for odds ratios in regard to weight gain, overweight/obesity, or abdominal obesity. 24 studies (27 reports) met the inclusion criteria for the systematic review, and 22 studies provided sufficient data for inclusion in the meta-analysis. The meta-analysis of the five studies on changes in body weight per serving of dairy no significant results could be found for whole fat dairy and low fat dairy. However, there was inverse association between changes in body weight for each serving's increase of yogurt (beta: -40.99 gram/year, 95% CI, -48.09 to -33.88), whereas each serving's increase of cheese was positively associated (beta: -10.97 gram/year, 95% CI, 2.86 to 19.07). Furthermore, the highest dairy intake category was associated with a reduced risk of abdominal obesity (OR: 0.85; 95% CI, 0.76 to 0.95), and risk of overweight (OR: 0.87; 95% CI, 0.76 to 1.00) compared to the lowest intake category. No significant association could be observed for risk of weight gain. In summary the results of the meta-analysis still reflect that dairy consumption was not positively related to changes in body weight. Yogurt was the only dairy food that showed some evidence for a beneficial effect, where higher intakes were inversely associated a reduced risk of obesity, changes in body weight or waist circumference. Further research is needed, since the overall interpretation of the results is limited by heterogeneous risk estimates.

Although clozapine is the gold-standard for treatment refractory schizophrenia, it has the worst metabolic profile of all antipsychotics. This is partly mediated by clozapine's impact on glucagon-like peptide (GLP-1). There is an absence of robust evidence for effective treatments for clozapine associated weight gain and metabolic syndrome. Metformin, with its role in increasing GLP-1 may aid weight loss among people on clozapine. We conducted a systematic-review and meta-analysis of metformin versus placebo for change in weight and metabolic syndrome for people on clozapine without diabetes mellitus. We searched the Cochrane Schizophrenia Group's trial register, Pubmed and Embase, as well as the following Chinese databases: the Chinese Biomedical Literature Service System and China Knowledge Resource Integrated Database. This was supplemented by hand searches of key papers. Eight studies, of which three were from Chinese databases, with 478 participants were included. We found that metformin was superior to placebo in terms of weight loss (-3.12kg, 95%CI -4.88kg to -1.37kg) and BMI (-1.18kg/m2, 95%CI -1.76kg/m2 to -0.61kg/m2). Metformin significantly improved three of the five components of metabolic syndrome; waist circumference, fasting glucose and triglycerides. Sensitivity analysis on study quality and duration did not greatly impact results. Metformin led to clinically meaningful weight loss among people on clozapine, and may reduce the rates of metabolic syndrome. Inclusion of metformin into the treatment protocols of people on clozapine, as tolerated, should be considered. PROSPERO registration number: CRD42015029723.