The impact of metformin on weight and metabolic parameters in patients with obesity: A systematic review and meta-analysis of randomized controlled trials.

There are conflicting data on the weight-reducing potential of metformin (MTF) in nondiabetic patients with obesity. The purpose of this systematic review and meta-analysis was to evaluate the effect of MTF on weight and cardiometabolic parameters in adults with overweight/obesity with or without nonalcoholic fatty liver disease (NAFLD) (CRD42018085512). We included randomized controlled trials (RCTs) in adults without diabetes mellitus, with mean body mass index (BMI) ≥ 25 kg/m2, with or without NAFLD, comparing MTF to placebo/control, lifestyle modification (LSM) or a US Food and Drug Administration-approved anti-obesity drug, reporting on weight or metabolic parameters, and extending over at least 3 months. We conducted a systematic search in MEDLINE, EMBASE, PubMed and the Cochrane Library without time limitation (until March 2022). We screened and selected eligible articles, abstracted relevant data, and assessed the risk of bias. All steps were in duplicate and independently. We conducted a random-effects model meta-analysis using Review Manager version 5.3, with prespecified subgroup analyses in case of heterogeneity. We identified 2650 citations and included 49 trials (55 publications). Compared to placebo, MTF was associated with a significant reduction in BMI (mean difference [MD] -0.56 [-0.74, -0.37] kg/m2; p < 0.0001), at doses ranging from 500 to 2550 mg/day, and with a significant percentage change in BMI of -2.53% (-2.90, -2.17) at the dose 1700 mg/day. There was no interaction by baseline BMI, MTF dose or duration, nor presence or absence of NAFLD. There was no significant difference between MTF and LSM. Orlistat was more effective than MTF (at doses of 1000-1700 mg/day) in terms of weight loss, with an MD in BMI of -3.17 (-5.88; -0.47) kg/m2, favouring the former. Compared to placebo/control, MTF improved insulin parameters, while no effect was detected when compared to LSM. A few small trials showed heterogenous effects on liver parameters in patients with NAFLD treated with MTF compared to placebo/control. There was a large variability in the expression of outcome measures and RCTs were of low quality. In conclusion, MTF was associated with a modest weight reduction in obese nondiabetic patients. Further high-quality and better powered studies are needed to examine the impact of MTF in patients with insulin resistance and NAFLD.

Mortality risk in patients with obesity and COVID-19 infection: a systematic review and meta-analysis.

Obesity is a risk factor for severe respiratory diseases, including COVID-19 infection. Meta-analyses on mortality risk were inconsistent. We systematically searched 3 databases (Medline, Embase, CINAHL) and assessed the quality of studies using the Newcastle-Ottawa tool (CRD42020220140). We included 199 studies from US and Europe, with a mean age of participants 41.8-78.2 years, and a variable prevalence of metabolic co-morbidities of 20-80 %. Exceptionally, one third of the studies had a low prevalence of obesity of <20 %. Compared to patients with normal weight, those with obesity had a 34 % relative increase in the odds of mortality (p-value 0.002), with a dose-dependent relationship. Subgroup analyses showed an interaction with the country income. There was a high heterogeneity in the results, explained by clinical and methodologic variability across studies. We identified one trial only comparing mortality rate in vaccinated compared to unvaccinated patients with obesity; there was a trend for a lower mortality in the former group. Mortality risk in COVID-19 infection increases in parallel to an increase in BMI. BMI should be included in the predictive models and stratification scores used when considering mortality as an outcome in patients with COVID-19 infections. Furthermore, patients with obesity might need to be prioritized for COVID-19 vaccination.

Comparison of Postoperative Outcomes of Trans-urethral Resection of the Prostate, Laser Vaporization, and Laser Enucleation: A Double Propensity Score Matched Analysis.

OBJECTIVE: To compare postoperative outcomes of 3 types of endourologic surgeries (trans-urethral resection of the prostate [TURP], laser vaporization [LVP], and laser enucleation [LEP]) for benign prostatic hypertrophy (BPH) treatment using the ACS-NSQIP database. METHODS: The ACS-NSQIP database was queried for men who underwent TURP, PVP, and LEP for treatment of BPH from 2011 till 2019. Demographics, clinical, operative characteristics, and 30-day outcomes were compared. Univariate and multivariate regression models were constructed. Propensity score matching was then performed as a sensitivity analysis. RESULTS: A total of 74,273 patients underwent endourologic surgeries for BPH, 65.4% had TURP, 28.6% PVP, and 5.9% LEP. Patients undergoing TURP were more likely to be older with higher ASA class, abnormal labs, and comorbidities (diabetic, congestive heart failure, and bleeding requiring transfusion) (P-value <.001). After adjusting for covariates and propensity score matching, LVP demonstrated shorter hospital stays, shorter operative times, less reoperation rates, decreased DVT/PE risk, with, however, higher odds of urinary tract infection and sepsis as compared to TURP (P-value<.028). Furthermore, LEP was found to have shorter hospital stays, longer operative times, and decreased odds of urinary tract infections and sepsis as compared to TURP (P-value<.006). CONCLUSION: LVP and LEP showed better surgical outcomes and characteristics as compared to TURP. Further research is needed to account for longer duration of follow-up and patient-specific urologic outcomes, such as prostate size, urinary incontinence, erectile dysfunction, and retrograde ejaculation.

Pharmacotherapy of obesity: an update on the available medications and drugs under investigation.

Obesity is an epidemic and a public health threat. Medical weight management remains one of the options for the treatment of excess weight and recent advances have revolutionized how we treat, and more importantly how we will be treating obesity in the near future. Metreleptin and Setmelanotide are currently indicated for rare obesity syndromes, and 5 other medications (orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide, semaglutide) are approved for non-syndromic obesity. Tirzepatide is about to be approved, and other drugs, with exciting novel mechanisms of action primarily based on incretins, are currently being investigated in different phases of clinical trials. The majority of these compounds act centrally, to reduce appetite and increase satiety, and secondarily, in the gastrointestinal tract to slow gastric emptying. All anti-obesity medications improve weight and metabolic parameters, with variable potency and effects depending on the specific drug. The currently available data do not support a reduction in hard cardiovascular outcomes, but it is almost certain that such data are forthcoming in the very near future. The choice of the anti-obesity medication needs to take into consideration the patient's clinical and biochemical profile, co-morbidities, and drug contra-indications, as well as expected degree of weight loss and improvements in cardio-renal and metabolic risk. It also remains to be seen whether precision medicine may offer personalized solutions to individuals with obesity, and whether it may represent the future of medical weight management along with the development of novel, very potent, anti-obesity medications currently in the pipeline. Funding: None.

The effect of aspartame and sucralose intake on body weight measures and blood metabolites: role of their form (solid and/or liquid) of ingestion.

The ingestion of non-caloric sweeteners (NCS) from food and/or drink was intended to reduce caloric intake without compromising palatability. However, the inconclusive relation between NCS and body weight may partially relate to their form of ingestion (solid or liquid). Thus, two paralleled experiments (aspartame and sucralose) were conducted. In each, Sprague Dawley rats (7-week-old male) were randomly divided into four groups. In Expt 1, aspartame (0·05 %) was added to the diet (AD) or drinking water (AW) or both diet and water (ADW), and a control group (C) was given a non-sweetened diet with plain water. In Expt 2, sucralose (0·016 %) was similarly provided in the diet (SD) or drinking water (SW) or both diet and water (SDW), with a control group (C). All rats had free access to food and water for 7 weeks. Energy intake, body weight and body composition were monitored and blood metabolites were determined. Results showed that aspartame ingestion significantly increased body weight and fat mass mainly due to an increase in energy efficiency. The effect was related to the amount rather than the form of ingestion. Additionally, aspartame ingestion was associated with glucose intolerance. Sucralose ingestion had a similar impact to that of aspartame though to a lesser extent. In conclusion, 7-week ingestion of aspartame and sucralose had adverse effects on body measures that were not related to the form of ingestion.