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International Journal of Obesity (2005) Aug 2023Recent studies suggest that tirzepatide, a dual glucose-dependent insulinotropic-peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA), has significant... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recent studies suggest that tirzepatide, a dual glucose-dependent insulinotropic-peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA), has significant weight loss effects. This systematic review and meta-analysis aims to assess the efficacy and safety of tirzepatide for weight loss in patients with overweight or obesity.
METHODS
Medline, Embase and Cochrane CENTRAL were searched for randomized controlled trials (RCTs) on tirzepatide's weight loss efficacy for these patients. A single arm meta-analysis of proportions estimated primary outcomes, ≥5%, ≥10%, and ≥15% weight loss, and adverse events (AEs); while meta-analysis of means estimated secondary outcomes. Comparative meta-analysis was conducted between tirzepatide and control arms where mean differences and odds ratios were estimated for continuous and dichotomous outcomes respectively.
RESULTS
RCTs included in this study revealed that among 5800 patients, 78.22% (95% CI: 72.15% to 83.73%), 55.60% (95% CI: 46.54% to 64.47%), 32.28% (95% CI: 23.17% to 42.12%) achieved ≥5%, ≥10%, and ≥15% weight loss, respectively. Tirzepatide 5 mg demonstrated weight loss superiority relative to placebo (MD: -12.47 kg, 95% CI: -13.94 kg to -11.00 kg) and semaglutide (n = 1409, MD: -1.90 kg, 95% CI: -2.97 kg to -0.83 kg) with dose-dependent increase for 10 mg and 15 mg doses. The comparison between tirzepatide and semaglutide was examined in the SURPASS-2 trial that was included in this systematic review. For AEs, there was increase odds of experiencing gastrointestinal AEs with tirzepatide compared to placebo, but no significant difference with semaglutide.
CONCLUSION
Tirzepatide has significant potential as a weight loss drug in patients with overweight and obesity, with little increase in AEs compared to other weight loss drugs. With its ability to concurrently target multiple aspects of metabolic syndrome, it should be considered as the next helm of weight loss therapies.
Topics: Humans; Overweight; Obesity; Gastric Inhibitory Polypeptide; Anti-Obesity Agents; Weight Loss; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Glucagon-Like Peptide-1 Receptor
PubMed: 37253796
DOI: 10.1038/s41366-023-01321-5 -
Fertility and Sterility Dec 2023The impact of paternal obesity and metabolic disease on semen quality and fertility outcomes is not fully appreciated. With increasing obesity rates, researchers have... (Review)
Review
The impact of paternal obesity and metabolic disease on semen quality and fertility outcomes is not fully appreciated. With increasing obesity rates, researchers have studied the intricate relationship between paternal body mass index, metabolic health, and male fertility. This systematic review identified 112 articles in the MEDLINE database between 2013 and 2023 that investigated the effects of body mass index, diabetes, metabolic syndrome, exercise, weight loss medication, or bariatric surgery on semen parameters, sperm quality, or fertility outcomes. This review suggests that obesity, diabetes, and metabolic syndrome have a negative impact on various parameters of male fertility, from semen quality to sperm deoxyribonucleic acid integrity. There is also mounting evidence that male obesity is correlated negatively with live births via both natural conception and assisted reproductive technologies. Lifestyle interventions, such as physical exercise, generally appear to improve male fertility markers; however, the type and intensity of exercise may play a crucial role. Pharmacologic treatments for weight loss, such as metformin and glucagon-like peptide 1 agonists, present a more complex picture, with studies suggesting both beneficial and detrimental effects on male reproductive health. Similarly, surgical interventions, such as gastric bypass surgery, show promise in improving hormonal imbalances but have mixed effects on semen parameters. Future research is needed to clarify these associations and inform clinical guidelines. In the interim, health practitioners should incorporate these insights into clinical practices, encouraging proactive lifestyle changes and providing targeted treatments to improve male reproductive health.
Topics: Male; Humans; Semen Analysis; Semen; Metabolic Syndrome; Obesity; Infertility, Male; Fertility; Weight Loss; Diabetes Mellitus
PubMed: 37839720
DOI: 10.1016/j.fertnstert.2023.10.017 -
Endocrine Practice : Official Journal... Feb 2024Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially for type 2 diabetes mellitus, show promise in promoting weight loss and improving heart health in obese... (Meta-Analysis)
Meta-Analysis Review
Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists on Body Weight and Cardiometabolic Parameters in Individuals With Obesity and Without Diabetes: A Systematic Review and Meta-Analysis.
OBJECTIVE
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially for type 2 diabetes mellitus, show promise in promoting weight loss and improving heart health in obese individuals without diabetes. Our goal was to examine existing research for conclusive evidence on various types of GLP-1 RAs for weight loss and cardiometabolic benefits in obesity without diabetes.
METHODS
We conducted an electronic search on PubMed, Scopus, and Cochrane Central using keywords, such as "GLP-1 RA," "obesity," and "weight loss." We considered all available global GLP-1 RAs for inclusion. Our analysis focused on weight loss, blood pressure (BP) changes (systolic and diastolic BPs), and lipid profile effects (high-density lipoprotein, low-density lipoprotein, total cholesterol, and triacylglycerol). We used a random-effects meta-analysis with the standardized mean difference (SMD), mean difference (MD), odds ratio, and relative risk to present the results.
RESULTS
Our search yielded a total of 7535 articles. We included 15 trials in our study. GLP-1 RAs led to significant weight loss (MD, -8.77 kg; P <.01) in obese individuals. GLP-1 RAs also improved the systolic BP (MD, -4.13 mm Hg; P <.01), diastolic BP (MD, -1.39 mm Hg; P <.01), and lipid profiles, including improved levels of triacylglycerol (SMD, -0.99 mg/dL; P <.01), total cholesterol (SMD, -0.73 mg/dL; P <.01), very low-density lipoprotein (SMD, -1.11 mg/dL; P <.01), and low-density lipoprotein (SMD, -0.27 mg/dL; P <.01), and significantly increased high-density lipoprotein levels (SMD, 0.11 mg/dL; P <.01). However, GLP-1 RAs were associated with an increased risk of gastrointestinal adverse events.
CONCLUSION
GLP-1 RAs were found to be beneficial for not only weight loss but also reduction in risk factors for cardiovascular disease such as BP and lipid profile. Consistent beneficial results were observed across the various subtypes of GLP-1 RAs.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Glucagon-Like Peptide-1 Receptor Agonists; Glucagon-Like Peptide 1; Obesity; Cardiovascular Diseases; Weight Loss; Lipids; Triglycerides; Lipoproteins, HDL; Lipoproteins, LDL; Cholesterol; Glucagon-Like Peptide-1 Receptor
PubMed: 38029929
DOI: 10.1016/j.eprac.2023.11.007 -
Antimicrobial Agents and Chemotherapy May 2024The prevalence of obesity has increased considerably in the last few decades. Pathophysiological changes in obese patients lead to pharmacokinetic (PK) and...
The prevalence of obesity has increased considerably in the last few decades. Pathophysiological changes in obese patients lead to pharmacokinetic (PK) and pharmacodynamic (PD) alterations that can condition the correct exposure to antimicrobials if standard dosages are used. Inadequate dosing in obese patients can lead to toxicity or therapeutic failure. In recent years, additional antimicrobial PK/PD data, extended infusion strategies, and studies in critically ill patients have made it possible to obtain data to provide a better dosage in obese patients. Despite this, it is usually difficult to find information on drug dosing in this population, which is sometimes contradictory. This is a comprehensive review of the dosing of different types of antimicrobials (antibiotics, antifungals, antivirals, and antituberculosis drugs) in obese patients, where the literature on PK and possible dosing strategies in obese adults was critically assessed.
Topics: Humans; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Antitubercular Agents; Antiviral Agents; Critical Illness; Obesity
PubMed: 38526051
DOI: 10.1128/aac.01719-23 -
Journal of Hepatology Aug 2023The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing. We aimed to estimate the pooled global NAFLD incidence. (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing. We aimed to estimate the pooled global NAFLD incidence.
METHODS
We performed a systematic review and meta-analysis of cohort studies of adults without NAFLD at baseline to evaluate the global incidence of ultrasound-diagnosed NAFLD.
RESULTS
A total of 63 eligible studies (1,201,807 persons) were analyzed. Studies were from Mainland China/Hong Kong (n = 26), South Korea (n = 22), Japan (n = 14), other (n = 2, Sri Lanka, Israel); 63.8% were clinical center studies; median study year 2000 to 2016; 87% were good quality. Among the 1,201,807 persons at risk, 242,568 persons developed NAFLD, with an incidence rate of 4,612.8 (95% CI 3,931.5-5,294.2) per 100,000 person-years and no statistically significant differences by study sample size (p = 0.90) or study setting (p = 0.055). Males had higher incidence vs. females (5,943.8 vs. 3,671.7, p = 0.0013). Both the obese (vs. non-obese) and the overweight/obese groups (vs. normal weight) were about threefold more likely to develop NAFLD (8,669.6 vs. 2,963.9 and 8,416.6 vs. 3,358.2, respectively) (both p <0.0001). Smokers had higher incidence than non-smokers (8,043.2 vs. 4,689.7, p = 0.046). By meta-regression, adjusting for study year, study setting, and study location, study period of 2010 or after and study setting were associated with increased incidence (p = 0.010 and p = 0.055, respectively). By country, China had a higher NAFLD incidence compared to non-China regions (p = 0.012) and Japan a lower incidence compared to non-Japan regions (p = 0.005).
CONCLUSIONS
NAFLD incidence is increasing with a current estimate of 4,613 new cases per 100,000 person-years. Males and overweight/obese individuals had significantly higher incidence rates compared to females and those of normal weight. Public health interventions for prevention of NAFLD are needed with a special emphasis on males, overweight/obese individuals, and higher risk regions.
IMPACT AND IMPLICATIONS
Non-alcoholic fatty liver disease (NAFLD) affects approximately 30% of people worldwide and appears to be increasing, but data to estimate the incidence rate are limited. In this meta-analytic study of over 1.2 million people, we estimated an incidence rate of NAFLD of 46.13 per 1,000 person-years with significant differences by sex, BMI, geography, and time-period. As treatment options for NAFLD remain limited, prevention of NAFLD should remain the focus of public health strategies. Studies such as these can help policy makers in determining which and whether their interventions are impactful.
Topics: Male; Adult; Female; Humans; Non-alcoholic Fatty Liver Disease; Incidence; Overweight; Obesity; Cohort Studies
PubMed: 37040843
DOI: 10.1016/j.jhep.2023.03.040 -
Advanced Biology Aug 2023Obesity often results in severe negative health consequences and represents a growing issue for global health. Reducing food intake is a crucial factor for weight loss.... (Review)
Review
Obesity often results in severe negative health consequences and represents a growing issue for global health. Reducing food intake is a crucial factor for weight loss. Intermittent fasting is a relatively new intervention that contributes to weight reduction. Considering the intimate relationship between obesity and inflammatory pathologies with gut microbiota alterations, a systematic review of the literature was herein conducted to elucidate the relationship between time-restricted food intake and gut microbiota diversity in humans. Searches are carried out in three databases (PubMed, MedLine/OVID, and Academic Search Complete) between April 2019 and April 2022. Nine studies (all with longitudinal design) were identified as eligible by presenting data about the impact of intermittent fasting schemes on gut microbiota. At the phylum level, Firmicutes and Bacteroidetes increase throughout follow-ups, while 16 bacteria genera change their abundance in response to intermittent fasting. Finally, some genera associated with clinical predictors such as weight change, abdominal circumference, and metabolic variables were reported. Changes induced by fasting schemes positively impact the diversity and abundance of gut microbiota and the biomarkers described here. However, the changes previously reported have been studied in short periods and some return to their basal state after fasting intervention.
Topics: Humans; Animals; Obesity; Gastrointestinal Microbiome; Intermittent Fasting; Inflammation; Bacteria
PubMed: 36950759
DOI: 10.1002/adbi.202200337 -
Diabetes, Obesity & Metabolism Sep 2023To compare the benefits and harms of drugs approved for weight management in adults with obesity or overweight. (Meta-Analysis)
Meta-Analysis
AIM
To compare the benefits and harms of drugs approved for weight management in adults with obesity or overweight.
MATERIALS AND METHODS
We performed a systematic review of drugs approved for treating obesity and overweight. We searched MEDLINE, Embase and CENTRAL through 26 February 2023. Random-effects network meta-analysis was applied.
RESULTS
A total of 168 trials (97 938 patients) were included. There was no evidence that drugs approved for weight management had different associations with cardiovascular death (69 trials, 59 037 participants). Naltrexone/bupropion was associated with lower cardiovascular mortality than placebo (odds ratio [OR], 0.62 [95% CI: 0.39, 0.99]; low certainty evidence). All drugs were associated with greater weight loss at 12 months than placebo (33 trials, 37 616 participants), mainly semaglutide (mean difference [MD], -9.02 kg [95% CI: -10.42, -7.63]; moderate certainty) and phentermine/topiramate (MD, -8.10 kg [95% CI: -10.14, -6.05]; high certainty); and with greater waist circumference reduction at 12 months than placebo (24 trials, 35 733 participants), mainly semaglutide (MD, -7.84 cm [95% CI: -9.34, -6.34]; moderate certainty) and phentermine/topiramate (MD, -6.20 cm [95% CI: -7.46, -4.94]; high certainty). Semaglutide and phentermine/topiramate were associated with lower or no difference in the odds of treatment withdrawal compared with all other drugs (87 trials, 70 860 participants).
CONCLUSIONS
Among adults with obesity or overweight, semaglutide and phentermine/topiramate were associated with greater body weight loss and waist circumference reduction at 12 months than all other drugs, and lower or no significant difference in risks of withdrawal. There was no evidence that drugs approved for weight management had different associations with cardiovascular death.
Topics: Adult; Humans; Overweight; Topiramate; Network Meta-Analysis; Randomized Controlled Trials as Topic; Obesity; Phentermine
PubMed: 37254688
DOI: 10.1111/dom.15138 -
Frontiers in Endocrinology 2023A systematic review and meta-analysis was conducted to synthesize the available data from clinical trials and assess the safety issues of tirzepatide (pancreatitis and... (Meta-Analysis)
Meta-Analysis
PURPOSE
A systematic review and meta-analysis was conducted to synthesize the available data from clinical trials and assess the safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes (T2D) and obesity.
METHODS
A systematic search was conducted in three electronic databases, namely Embase, PubMed, and the Cochrane Library, up until March 1, 2023, to identify randomized controlled trials (RCTs) comparing tirzepatide to either placebo or active hypoglycemic drugs in individuals with T2D and obesity. Heterogeneity was assessed using the I2 value and Cochran's Q test, and a fixed effects model was employed to estimate the safety profile of tirzepatide. The safety outcomes of interest, including pancreatitis, the composite of gallbladder or biliary diseases, cholecystitis, and cholelithiasis and biliary diseases, were evaluated. (The composite of gallbladder or biliary diseases incorporated cholelithiasis, cholecystitis, other gallbladder disorders, and biliary diseases.).
RESULTS
A total of nine trials with 9871 participants (6828 in the tirzepatide group and 3043 in the control group) that met the pre-specified criteria were included. When compared to all control groups consisting of basal insulin (glargine or degludec), selective GLP1-RA (dulaglutide or semaglutide once weekly), and placebo, an increased risk of pancreatitis was not found to be significantly associated with tirzepatide (RR 1.46, [95% CI] 0.59 to 3.61; I2 = 0.0%, p = 0.436). For gallbladder or biliary disease, the composite of gallbladder or biliary disease was significantly associated with tirzepatide compared with placebo or basal insulin (RR 1.97, [95% CI] 1.14 to 3.42; I2 = 0.0%, p = 0.558), but not with the risk of cholelithiasis, cholecystitis or biliary diseases.
CONCLUSION
Based on the currently available data, tirzepatide appears to be safe regarding the risk of pancreatitis. However, the increased risk of the composite outcome of gallbladder or biliary diseases observed in RCTs warrants further attention from physicians in clinical practice.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023412400.
Topics: Humans; Cholecystitis; Diabetes Mellitus, Type 2; Insulin Glargine; Obesity; Pancreatitis; Cholelithiasis
PubMed: 37908750
DOI: 10.3389/fendo.2023.1214334 -
British Journal of Sports Medicine Aug 2023To determine and compare the dose-response effects of exercise and caloric restriction on visceral adipose tissue in overweight and obese adults, while controlling for... (Meta-Analysis)
Meta-Analysis Review
Dose-response effects of exercise and caloric restriction on visceral adiposity in overweight and obese adults: a systematic review and meta-analysis of randomised controlled trials.
OBJECTIVE
To determine and compare the dose-response effects of exercise and caloric restriction on visceral adipose tissue in overweight and obese adults, while controlling for the weekly energy deficit induced by the interventions.
METHODS
PubMed, Embase, CINAHL and Web of Science were searched for randomised controlled trials comparing exercise or caloric restriction against eucaloric controls in overweight or obese adults. The primary outcome was the change in visceral fat measured by CT or MRI. Meta-analyses and meta-regressions were performed to determine the overall effect size (ES) and the dose-dependent relationship of exercise and caloric restriction on visceral fat. Heterogeneity, risk of bias and the certainty of evidence were also assessed.
RESULTS
Forty randomised controlled trials involving 2190 participants were included. Overall, exercise (ES -0.28 (-0.37 to -0.19); p<0.001; I=25%) and caloric restriction (ES -0.53 (-0.71 to -0.35); p<0.001; I=33%) reduced visceral fat compared with the controls. Exercise demonstrated a dose-response effect of -0.15 ((-0.23 to -0.07); p<0.001) per 1000 calories deficit per week, whereas the effect of caloric restriction was not dose-dependent (ES 0.03 (-0.12 to 0.18); p=0.64). Most of the studies showed a moderate risk of bias.
CONCLUSIONS
These findings support the dose-dependent effects of exercise to reduce visceral fat in overweight and obese adults. Caloric restriction did not demonstrate a dose-response relationship, although this may be attributed to the smaller number of studies available for analysis, compared with exercise studies.
PROSPERO REGISTRATION NUMBER
CRD42020210096.
Topics: Adult; Humans; Overweight; Adiposity; Obesity; Exercise; Intra-Abdominal Fat; Randomized Controlled Trials as Topic
PubMed: 36669870
DOI: 10.1136/bjsports-2022-106304 -
Metabolism: Clinical and Experimental Dec 2023The present systematic review aimed to synthesize available data from recently published randomized trials (RCTs) investigating the efficacy and safety of the novel,... (Meta-Analysis)
Meta-Analysis
Safety and efficacy of the new, oral, small-molecule, GLP-1 receptor agonists orforglipron and danuglipron for the treatment of type 2 diabetes and obesity: systematic review and meta-analysis of randomized controlled trials.
AIMS
The present systematic review aimed to synthesize available data from recently published randomized trials (RCTs) investigating the efficacy and safety of the novel, orally administered, small-molecule glucagon-like peptide 1 receptor agonists (GLP-1RAs) orforglipron and danuglipron for the treatment of type 2 diabetes mellitus (T2DM), obesity or both.
METHODS
Literature search was performed through Medline (via PubMed), Cochrane Library and Scopus until August 16, 2023. Double-independent study selection, data extraction and quality assessment were performed. Evidence was pooled with random effects meta-analysis.
RESULTS
Totally, 1037 patients among seven RCTs were analyzed. All RCTs had low risk of bias according to the Cochrane Collaboration tool (RoB2). Novel GLP-1RAs led to significant reduction in HbA1c in patients with T2DM compared to controls (MD = -1.03 %; 95 % CI = [-1.29, -0.77]; P < 0.001). A significantly greater weight reduction was also noted both in patients with T2DM or obesity compared to controls (MD = -3.26 kg; 95 % CI = [-4.79, -1.72]; P < 0.001 and MD = -7.52 kg; 95 % CI = [-14.63, -0.41]; P = 0.038, respectively; P for subgroup differences = 0.25). Regarding safety, novel GLP-1RAs showed a neutral effect on the odds of severe hypoglycemia or serious adverse events (OR = 0.34; 95 % CI = [0.09, 1.31]; P = 0.11 and OR = 0.95; 95 % CI = [0.39, 2.34]; P = 0.91, respectively) and significantly higher odds of gastrointestinal, treatment-emergent adverse events (OR = 2.57; 95 % CI = [1.49, 4.42]; P < 0.001) and adverse events leading to discontinuation (OR = 2.89; 95 % CI = [1.22, 6.87]; P = 0.016).
CONCLUSION
Preliminary evidence supports that orforglipron and danuglipron are efficient in glycemic control and weight reduction in T2DM, obesity or both. More longitudinal research is warranted in order to provide deeper insights into their efficacy, safety and tolerability before their potential incorporation in the pharmacological arsenal against T2DM or obesity.
Topics: Humans; Glucagon-Like Peptide-1 Receptor; Randomized Controlled Trials as Topic; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Obesity; Weight Loss
PubMed: 37852529
DOI: 10.1016/j.metabol.2023.155710