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.

Vitamin D Supplementation and Fractures in Adults: A Systematic Umbrella Review of Meta-Analyses of Controlled Trials.

CONTEXT: The growing number of systematic reviews/meta-analyses (SR/MAs) on vitamin D (±â€…calcium) for fracture prevention has led to contradictory guidelines. OBJECTIVE: This umbrella review aims to assess the quality and explore the reasons for the discrepancy of SR/MAs of trials on vitamin D supplementation for fracture risk reduction in adults. METHODS: We searched 4 databases (2010-2020), Epistemonikos, and references of included SRs/MAs, and we contacted experts in the field. We used A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR-2) for quality assessment. We compared results and investigated reasons for discordance using matrices and subgroup analyses (PROSPERO registration: CRD42019129540). We included 13 SR/MAs on vitamin D and calcium (Ca/D) and 19 SR/MAs on vitamin D alone, compared to placebo/control. RESULTS: Only 2 from 10 SRs/MAs on Ca/D were of moderate quality. Ca/D reduced the risk of hip fractures in 8 of 12 SRs/MAs (relative risk [RR] 0.61-0.84), and any fractures in 7 of 11 SR/MAs (RR 0.74-0.95). No fracture risk reduction was noted in SRs/MAs exclusively evaluating community-dwelling individuals or in those on vitamin D alone compared to placebo/control. Discordance in results between SRs/MAs stems from inclusion of different trials, related to search periods and eligibility criteria, and varying methodology (using intention to treat, per-protocol, or complete case analysis from individual trials). CONCLUSION: Ca/D reduces the risk of hip and any fractures, possibly driven by findings from institutionalized individuals. Individual participant data meta-analyses of patients on Ca/D with sufficient follow-up periods, and subgroup analyses, would unravel determinants for a beneficial response to supplementation.

Risk of Postoperative Renal Failure in Radical Nephrectomy and Nephroureterectomy: A Validated Risk Prediction Model.

INTRODUCTION: The study aimed to construct and validate a risk prediction model for incidence of postoperative renal failure (PORF) following radical nephrectomy and nephroureterectomy. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database years 2005-2014 were used for the derivation cohort. A stepwise multivariate logistic regression analysis was conducted, and the final model was validated with an independent cohort from the ACS-NSQIP database years 2015-2017. RESULTS: In cohort of 14,519 patients, 296 (2.0%) developed PORF. The final 9-factor model included age, gender, diabetes, hypertension, BMI, preoperative creatinine, hematocrit, platelet count, and surgical approach. Model receiver-operator curve analysis provided a C-statistic of 0.79 (0.77, 0.82; p < 0.001), and overall calibration testing R2 was 0.99. Model performance in the validation cohort provided a C-statistic of 0.79 (0.76, 0.81; p < 0.001). CONCLUSION: PORF is a known risk factor for chronic kidney disease and cardiovascular morbidity, and is a common occurrence after unilateral kidney removal. The authors propose a robust and validated risk prediction model to aid in identification of high-risk patients and optimization of perioperative care.

Vitamin D3 Dose Requirement That Raises 25-Hydroxyvitamin D to Desirable Level in Overweight and Obese Elderly.

CONTEXT: Guidelines for the dosage of vitamin D supplementation vary widely globally. OBJECTIVE: To investigate the impact of 2 vitamin D doses, bracketed between the IOM recommended dietary allowance (RDA) and the upper tolerable limit, on vitamin D nutritional status in elderly individuals. METHODS: This post hoc analysis of data collected from a 12-month, double-blind, randomized control trial included 221 ambulatory participants (≥ 65 years) with a mean BMI of 30.2 kg/m2 and a mean baseline serum 25-hydroxyvitamin D [25(OH)D] level of 20.4 ±â€…7.4 ng/mL, who were recruited from 3 outpatient centers in Lebanon. All participants received 1000 mg of elemental calcium daily from calcium citrate plus the daily equivalent of either 600 IU or 3750 IU of vitamin D3. RESULTS: Mean 25(OH)D level at 12 months was 26.0 ng/mL with low dose and 36.0 ng/mL with high dose vitamin D3. The proportion of participants reaching a value ≥ 20 ng/mL was 86% in the low dose, and 99% in the high dose arms, with no gender differences. The increment of 25(OH)D per 100 IU/day was 1 ng/mL with the low dose, and 0.41 ng/mL with the high dose. Serum 25(OH)D levels at 1 year were highly variable in both treatment arms. Baseline 25(OH)D level and vitamin D dose-but not age, BMI, gender, or season-were significant predictors of serum 25(OH)D level post-intervention. CONCLUSION: The IOM Recommended Dietary Allowance (RDA) of 600 IU/day does not bring 97.5% of ambulatory elderly individuals above the desirable threshold of 20 ng/mL. Country-specific RDAs are best derived taking into account the observed variability and predictors of achieved 25(OH)D levels.