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Obesity Management Pharmacotherapies and Lifestyle Treatment for Pediatric Obesity Management A Systematic Review and Network Meta-Analysis

Author/s: 
Ke-wen Wan, Evander Fung-chau Lei, Ying Liu, Asefa Adimasu Taddese, Patrick lp, Gabriel Torbahn, Daniel Weghuber, Wendy Y. Huang, Bjorn T.Tam

Abstract
Importance Pediatric obesity is a global health challenge. Although health behavior and lifestyle treatment (HBLT) is foundational, the comparative effectiveness of HBLT, various pharmacotherapies, and their combinations remains unclear.

Objective To compare the effectiveness of obesity management pharmacotherapies, structured lifestyle treatment, and their combinations on weight management outcomes in children and adolescents living with obesity.

Data Sources A systematic search was conducted in 4 electronic databases (Embase, CENTRAL, PsycINFO, and PubMed) from inception to June 17, 2025.

Data Selection Randomized clinical trials (RCTs) involving children and adolescents (aged 10-19 years) with obesity were selected. Interventions included lifestyle treatment (HBLT and counseling), obesity management pharmacotherapies (glucagon-like peptide-1 receptor agonists, metformin, orlistat, phentermine topiramate), or their combination vs control.

Data Extraction and Synthesis Data were extracted and validity assessed according to PRISMA guidelines. A random-effects network meta-analysis was used to pool data. Meta-regression was used to explore outcome moderators.

Main Outcomes and Measures Primary outcomes were body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and BMI z score; secondary outcomes included waist circumference (WC), fat mass (FM), and lean mass (LM).

Results A total of 42 RCTs with 3835 participants (median [IQR] age, 14.5 [13.3-15.1] years; 2270 female [59.2%]) were included. Treatments combining pharmacotherapy and lifestyle treatment demonstrated the greatest efficacy across all adiposity-related outcomes. Semaglutide plus counseling was associated with the largest BMI reduction (mean difference, −8.31; 95% CI, −12.33 to −4.28) and BMI z score reduction (mean difference, −1.80; 95% CI, −2.39 to −1.21), although this estimate was based on a limited number of studies. All pharmacological treatments were more effective when paired with lifestyle treatment, associated with significantly greater BMI and BMI z score reductions than the same medications alone. Based on the primary analysis, HBLT as monotherapy was associated with substantial decreases in BMI (mean difference, −3.85; 95% CI, −4.91 to −2.80) and BMI z score (mean difference, −0.89; 95% CI, −1.17 to −0.61) vs control.

Conclusions and Relevance Finding of this systematic review and network meta-analysis suggest that combining lifestyle treatment with obesity management medications was associated with the greatest short-term (typically 6 to 12 months) weight reduction in adolescents with obesity. HBLT remained an indispensable component of any effective weight management, delivering meaningful weight loss and healthier body composition on its own. Combined with lifestyle treatment, pharmacotherapy was a key component, not solely an adjunct, associated with the greatest BMI and BMI z score improvements, and long-term sustainability and safety were monitored.

Keywords 
pediatric obesity pharmacotherapy meta-analysis

Pharmacologic Treatment of Heart Failure With Reduced Ejection Fraction: An Updated Systematic Review and Network Meta-Analysis

Author/s: 
Bart J. van Essen, Daan C.H. Ceelen, Wouter Ouwerkerk, Tiew-Hwa K. Teng, Ganash N. Tharshana, Fook Ming Hew, Javed Butler, Faiez Zannad, Carolyn S. Lam, Justin Ezekowitz, Adriaan A. Voors, Jasper Tromp

Background: In 2022, a network meta-analysis showed that a combination of β-blockers, angiotensin receptor-neprilysin inhibitors (ARNi), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter 2 inhibitors (SGLT2i) was most effective in reducing all-cause mortality in heart failure with reduced ejection fraction (HFrEF). This study updates the treatment benefit by including additional large randomized controlled trials (RCTs) since 2022, including the VICTOR (Vericiguat Global Study in Participants with Chronic Heart Failure) trial.

Objectives: The goal of this study was to evaluate and compare regimens of pharmacotherapy in patients with HFrEF.

Methods: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases were searched for RCTs in patients with HFrEF through April 2025. Using frequentist network meta-analysis, HRs for all-cause mortality (primary outcome), cardiovascular death, and the composite of cardiovascular death or heart failure hospitalization (secondary outcomes) were estimated. Absolute benefits were quantified as life-years gained by using BIOSTAT-CHF (Biology Study to Tailored Treatment in Chronic Heart Failure) and ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) cohort data.

Results: The analysis included 103,754 patients across 89 randomized controlled trials. Relative to placebo, quintuple therapy with ARNi, β-blockers, MRAs, SGLT2i, and vericiguat most effectively reduced all-cause mortality (HR: 0.35; 95% CI: 0.27-0.45), followed by quadruple therapy with ARNi, β-blockers, MRAs, and SGLT2i (HR: 0.39; 95% CI: 0.32-0.49). For a representative 70-year-old patient, quadruple therapy (ARNi/β-blockers/MRAs/SGLT2i) provided 5.3 additional life-years (95% CI: 2.8-7.7) vs no treatment, while quintuple therapy (ARNi/β-blockers/MRA/SGLT2i/vericiguat) provided 6.0 additional life-years (95% CI: 3.7-8.4).

Conclusions: This analysis reinforces the substantial mortality and morbidity benefit associated with the currently recommended quadruple therapy regimen (ARNi, β-blockers, MRAs, and SGLT2i) in patients with HFrEF. The addition of vericiguat may provide an incremental survival gain of approximately 0.7 year beyond that achieved with quadruple therapy. However, these results should be regarded as exploratory, as they are derived from a secondary endpoint of a single trial.

Keywords: HFrEF; drug therapy; pharmacotherapy.

Keywords 
HFrEF drug therapy pharmacotherapy

Identifying and quantifying potentially problematic prescribing cascades in clinical practice: A mixed-methods study

Author/s: 
Atiya K Mohammad, Jacqueline G Hugtenburg, Joost W Vanhommerig

Background: A prescribing cascade occurs when medication causes an adverse drug reaction (ADR) that leads to the prescription of additional medication. Prescribing cascades can cause excess medication burden, which is of particular concern in older adults. This study aims to identify and quantify potentially problematic prescribing cascades relevant for clinical practice.

Methods: A mixed-methods study was conducted. First, prescribing cascades were identified through literature search. An expert panel (n = 16) of pharmacists and physicians assessed whether these prescribing cascades were potentially problematic. Next, a cohort study quantified potentially problematic prescribing cascades in adults using Dutch community pharmacy data for the period 2015-2020. Additionally, the influence of multiple medications potentially causing the same ADR was evaluated. Prescription sequence symmetry analysis was used to calculate adjusted sequence ratios (aSRs), adjusting for temporal prescribing trends. An aSR >1.0 indicates the occurrence of a prescribing cascade. In a subgroup analysis, aSRs were calculated for older adults.

Results: Seventy-six prescribing cascades were identified in literature and three were provided by experts. Of these, 66 (83.5%) were considered potentially problematic. A significant positive aSR for the medication sequence was found for 41 (62.1%) of these prescribing cascades. The highest aSR was found for amiodarone potentially causing hypothyroidism treated with thyroid hormones (4.63 [95% confidence interval 4.40-4.85]), based on 565 incident users. The biggest population (n = 34,645) was found for angiotensin converting enzyme-inhibitors potentially causing urinary tract infections treated with antibiotics. Regarding four potential ADRs, the aSRs were higher for people using multiple medications that cause the same ADR as compared to people using only one of those medications. Among older adults the aSRs remained significant for 37 prescribing cascades.

Conclusion: An overview was generated of potentially problematic prescribing cascades relevant for clinical practice. These results can support healthcare providers to intervene and reduce medication burden for older adults.

Keywords 
adverse drug reaction appropriate prescribing pharmacotherapy prescribing cascades prescription sequence symmetry analysis

Management of Chronic Heart Failure with Reduced Ejection Fraction

Author/s: 
Brandon Williamson, Carl Tong

Heart failure with reduced ejection fraction (HFrEF) is a commonly seen clinical entity in the family physician's practice. This clinical review focuses on the pharmacologic management of chronic HFrEF. Special attention is paid to the classification of heart failure and the newest recommendations from the American Heart Association concerning the use of guideline-directed medical therapy. β blockers, ACE inhibitors, ARBs, mineralocorticoid receptor antagonists are discussed in detail. The new emphasis on sacubitril-valsartan and SGLT2i's as therapies for HFrEF are reviewed, followed by a brief discussion of more advanced therapies and comorbidity management.

Keywords 
heart failure Reduced Ejection Fraction CHF pharmacotherapy HFrEF

Evidenced-Based Pharmacotherapies for Alcohol Use Disorder

Author/s: 
Fairbanks, J, Umbreit, A, Kolla, BP, Karpyak, VM, Schneekloth, TD, Loukianova, LL, Sinha, S

Pathologic alcohol use affects more than 2 billion people and accounts for nearly 6% of all deaths worldwide. There are three medications approved for the treatment of alcohol use disorder by the US Food and Drug Administration (FDA): disulfiram, naltrexone (oral and long-acting injectable), and acamprosate. Of growing interest is the use of anticonvulsants for the treatment of alcohol use disorder, although currently none are FDA approved for this indication. Baclofen, a γ-aminobutyric acid B receptor agonist used for spasticity and pain, received temporary approval for alcohol use disorder in France. Despite effective pharmacotherapies, less than 9% of patients who undergo any form of alcohol use disorder treatment receive pharmacotherapies. Current evidence does not support the use of pharmacogenetic testing for treatment individualization. The objective of this review is to provide knowledge on practice parameters for evidenced-based pharmacologic treatment approaches in patients with alcohol use disorder.

Keywords 
alcohol use disorder pharmacotherapy disulfiram naltrexone acamprosate anticonvulsants Baclofen

Pharmacotherapy for Adults With Alcohol Use Disorder (AUD) in Outpatient Settings

Author/s: 
John M. Eisenberg Center for Clinical Decisions and Communications Science

Focus of This Summary

This is a summary of a systematic review evaluating the evidence regarding the efficacy, comparative effectiveness, and adverse effects of medications in adults with alcohol use disorder (AUD). The systematic review included 167 articles reporting on 135 eligible studies published from January 1, 1970, to October 11, 2013. This summary is provided to inform discussions with patients and/or caregivers of treatment options and to assist in decisionmaking along with consideration of a patient's values and preferences. However, reviews of evidence should not be construed to represent clinical recommendations or guidelines.

Keywords 
alcohol use disorder pharmacotherapy patient care
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