Pharmacogenetic interactions of medications administered for weight loss in adults: a systematic review and meta-analysis.
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SUBMITTER: BouSaba J
PROVIDER: S-EPMC10152409 | biostudies-literature | 2023 Apr
REPOSITORIES: biostudies-literature
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Pharmacogenetic interactions of medications administered for weight loss in adults: a systematic review and meta-analysis.
BouSaba Joelle J Vosoughi Kia K Dilmaghani Saam S Prokop Larry J LJ Camilleri Michael M
Pharmacogenomics 20230331 5
<b>Aim:</b> To analyze roles of single nucleotide variants (SNVs) on weight loss with US FDA-approved medications. <b>Materials & methods:</b> We searched the literature up until November 2022. Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed. <b>Results:</b> 14 studies were included in qualitative analysis and seven in meta-analysis. SNVs in <i>CNR1</i>, <i>GLP-1R</i>, <i>MC4R</i>, <i>TCF7L2</i>, <i>CTRB1/2</i>, <i>ADIPOQ</i>, <i>SORCS1</i> and <i>ANKK ...[more]
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Project description:Background & aimsWe performed a systematic review and network meta-analysis to evaluate the overall and comparative effects of weight-loss medications approved by the Food and Drug Administration for long-term use on cardiometabolic risk profiles of obese adults.MethodsWe performed a systematic literature review through February 28, 2017 to identify randomized clinical trials of the effects of Food and Drug Administration-approved weight-loss medications (ie, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide) administered to obese adults for 1 year or more, compared with placebo or another active agent. Outcomes of interest included changes in blood glucose (fasting blood glucose [FBG] and hemoglobin A1c), cholesterol profile (low-density lipoprotein and high-density lipoproteins), blood pressure (BP; systolic/diastolic), and waist circumference (WC). We performed pair-wise and network meta-analyses with outcomes reported as weighted and standardized mean differences. Quality of evidence was rated using GRADE (Grading of Recommendations Assessment, Development and Evaluation).ResultsIn a meta-analysis of 28 randomized controlled trials (29,018 participants; median body mass index, 36.1 kg/m2), we associated weight-loss medications with a modest decrease in FBG (weighted mean difference, 4.0 mg/dL; 95% confidence interval, -4.4 to -3.6 mg/dL) and WC (weighted mean difference, reduction of 3.3 cm; 95% confidence interval, -3.5 to -3.1 cm), without clinically meaningful changes in systolic/diastolic BP or cholesterol profile vs placebo (standardized mean difference <0.2); effects varied among drugs. Phentermine-topiramate use was associated with a substantial decrease in WC and a modest decrease in FBG, hemoglobin A1c, and BP, and had minimal effect on cholesterol. Liraglutide use was associated with a substantial decrease in FBG, hemoglobin A1c, and WC, and a minimal effect on BP and cholesterol. Naltrexone-bupropion use was associated with moderate increase in high-density lipoprotein cholesterol, but had a minimal effect on FBG and WC. Orlistat use was associated with a decrease in low-density lipoprotein and high-density lipoprotein cholesterol. No drug improved all cardiometabolic risk factors.ConclusionsIn a systematic review and network meta-analysis, we found Food and Drug Administration-approved weight-loss medications to have only modest positive effects on cardiometabolic risk profile. Further research is needed to evaluate the long-term cardiometabolic benefits of these medications.ProsperoCRD42016039486.
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Project description:Non-alcoholic fatty liver disease (NAFLD) is a common comorbidity in individuals with obesity. Although multiple pharmacotherapeutics are in development, currently there are limited strategies specifically targeting NAFLD. This systematic review summarizes the existing literature on hepatic effects of medications used for weight loss. Glucagon-like peptide 1 (GLP-1) agonists are the best-studied in this regard, and evidence consistently demonstrates reduction in liver fat content, sometimes accompanied by improvements in histological features of steatohepatitis and reductions in serum markers of hepatic injury such as alanine aminotransferase (ALT). It remains unclear whether these benefits are independent of the weight loss caused by these agents. Literature is limited regarding effects of orlistat, but a small number of reports suggest that orlistat reduces liver fat content and improves histologic features of NASH, benefits which may also be driven primarily by weight loss. A sizeable body of literature on hepatic effects of metformin yields mixed results, with a probability of modest benefit, but no consistent signal for strong benefit. There are insufficient data on hepatic effects of topiramate, phentermine, naltrexone, bupropion, and lorcaserin. Finally, a few studies to date suggest that sodium-glucose co-transporter-2 (SGLT2) inhibitors may reduce liver fat content and cause modest reductions in ALT, but further study is needed to better characterize these effects. Based on available data, GLP-1 agonists have the strongest evidence base demonstrating beneficial effects on NAFLD, but it is not clear if any weight loss medication has effects on NAFLD superior to those of nutritional modification and exercise alone.
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Project description:ImportanceCurrent guidance on the duration of aerobic exercise recommended in existing guidelines comes primarily from individual trials. Meta-analyses are lacking to examine the dose-response association of aerobic exercise with adiposity measures.ObjectiveTo clarify the dose-response association of aerobic exercise with adiposity measures.Data sourcesPubMed, Scopus, the Cochrane Central Register of Controlled Trials, and gray literature sources (ProQuest and ClinicalTrials.gov) from inception to April 30, 2024.Study selectionRandomized clinical trials with intervention durations of at least 8 weeks evaluating the effects of supervised aerobic training on adults with overweight or obesity.Data extraction and synthesisThe PRISMA guidelines were followed to report the results of the meta-analysis. Data extraction was conducted by 2 teams of 2 reviewers each, working independently and in duplicate. Random-effects meta-analyses were performed to estimate mean differences and 95% CIs for each 30-minute per week aerobic exercise and to clarify the shape of the curvilinear associations.Main outcomes and measuresMeasures of body weight, waist circumference, body fat, adverse events, medication use reduction, and health-related quality of life score. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool, with a range from very low to high certainty.ResultsIn total, 116 randomized clinical trials involving 6880 participants (4199 [61%] female; mean [SD] age, 46 [13] years) with overweight or obesity were included. Each 30 minutes per week of aerobic exercise was associated with reduced body weight by 0.52 kg (95% CI, -0.61 to -0.44 kg; n = 109 trials, GRADE = moderate), waist circumference by 0.56 cm (95% CI, -0.67 to -0.45 cm; n = 62 trials, GRADE = high), body fat percentage by 0.37% (95% CI, -0.43% to -0.31%; n = 65 trials, GRADE = moderate), as well as the areas of visceral (mean difference, -1.60 cm2 [95% CI, -2.12 to -1.07 cm2]; n = 26 trials, GRADE = high) and subcutaneous (mean difference, -1.37 cm2 [95% CI, -1.82 to -0.92 cm2]; n = 27 trials, GRADE = moderate) adipose tissues. Aerobic exercise was associated with modestly increased physical (standardized mean difference, 1.69 SD [95% CI, 1.18-2.20 SD]) and mental (standardized mean difference, 0.74 SD [95% CI, 0.29-1.19 SD]) aspects of quality of life (1 trial with 80 participants, GRADE = low). It was associated with modestly increased mild to moderate adverse events, which were mostly musculoskeletal symptoms (risk difference, 2 more events per 100 participants [95% CI, 1 to 2 more]; GRADE = low). Dose-response meta-analyses indicated that body weight, waist circumference, and body fat measures decreased linearly or monotonically in association with increasing duration of aerobic exercise to 300 minutes per week, with aerobic exercise lasting 150 minutes per week at moderate to vigorous intensities resulting in clinically important reductions in waist circumference and body fat.Conclusions and relevanceIn this meta-analysis of randomized clinical trials, engaging in 30 minutes of aerobic exercise per week was associated with modest reductions in body weight, waist circumference, and body fat measures among adults with overweight or obesity. However, aerobic training exceeding 150 minutes per week at moderate intensity or greater may be needed to achieve clinically important reductions.
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