Review
This 2026 American College of Physicians (ACP) living clinical guideline synthesizes systematic reviews on pharmacologic treatments combined with lifestyle modifications for weight management in nonpregnant adults with overweight or obesity in outpatient settings, using the GRADE framework. For adults with obesity (BMI ≥30 kg/m²), the ACP issued conditional recommendations favoring semaglutide and tirzepatide as first-line agents (moderate-certainty evidence), phentermine-topiramate as second-line (low-certainty), liraglutide as third-line (low-certainty), and naltrexone-bupropion as fourth-line (low-certainty). For adults with overweight (BMI ≥27–30 kg/m²) who also have type 2 diabetes, dyslipidemia, hypertension, obstructive sleep apnea, or cardiovascular disease, the guideline conditionally recommends semaglutide and tirzepatide as first-line and liraglutide as second-line. All recommendations are conditional, reflecting the importance of shared decision-making around benefits, harms, costs, access, comorbidities, contraindications (e.g., cardiovascular contraindication and monthly pregnancy-test requirement for phentermine-topiramate; suicidal ideation risk with naltrexone-bupropion), and patient preferences. The living guideline format signals ongoing updates as new evidence emerges.
Annals of internal medicine · Jun 2026DOI ↗ Review
This systematic review, conducted for the American College of Physicians, evaluated the cost-effectiveness of pharmacologic treatments for overweight or obesity in U.S. adults. Researchers searched MEDLINE, Embase, and economic databases through October 2025, ultimately including 9 studies encompassing 42 pairwise treatment comparisons. Study quality was assessed using the CHEQUE tool, value was measured via incremental cost-effectiveness ratios (ICERs) against established willingness-to-pay thresholds, and certainty of evidence was graded using GRADE. Key findings from the 6 moderate-certainty studies suggested that liraglutide had low value compared with lifestyle modification, while phentermine-topiramate and tirzepatide showed high value versus lifestyle modification. Semaglutide demonstrated low value compared with naltrexone-bupropion and phentermine-topiramate, but high value compared with liraglutide. Important limitations include that all 9 included studies were model-based rather than empirical trial-based analyses, only 4 of 9 were at low risk of bias, none of the 42 comparisons reached high certainty, and reporting was frequently incomplete. The authors conclude that current U.S. evidence on cost-effectiveness of obesity pharmacotherapy is significantly hampered by poor study quality, restricting the strength of any conclusions that can be drawn.
Annals of internal medicine · Jun 2026DOI ↗ Review
This review examines the evolving medical management of short bowel syndrome intestinal failure (SBS-IF), a condition historically associated with lifelong dependence on home parenteral support (HPS) and, in select cases, intestinal transplantation (iTx). The authors describe how recent pharmacological advances—particularly glucagon-like peptide-2 (GLP-2) analogues and GLP-1 receptor agonists—have been integrated alongside conventional antimotility and antisecretory therapies to promote intestinal adaptation. The review argues that SBS-IF should now be understood as a dynamic and potentially modifiable form of organ failure rather than a static, irreversible condition. According to the authors, GLP-2 analogues represent the first pathophysiology-targeted, pro-adaptive therapies in this disease, while GLP-1 receptor agonists are highlighted as promising adjuncts, especially for patients with high-output phenotypes. The paper contends that multidisciplinary intestinal rehabilitation and gut-directed pharmacotherapy have meaningfully altered the natural history of SBS-IF, reducing HPS dependence and improving patient-centered outcomes. A key implication discussed is that iTx has been repositioned from a default end-stage intervention to a targeted rescue option used after optimized rehabilitation. Limitations include the review format, which synthesizes existing literature without presenting new primary data or meta-analytic pooling.
Current opinion in organ transplantation · Jun 2026DOI ↗ Review
This article provides practical, evidence-informed clinical guidance on incorporating oral semaglutide — the first oral glucagon-like peptide-1 (GLP-1) receptor agonist — into obesity management. The authors draw on data from clinical trials, including the OASIS 4 trial, as well as expert clinical insights. The paper highlights that oral semaglutide has demonstrated weight loss outcomes comparable to subcutaneous GLP-1 therapies, with associated improvements in cardiometabolic risk factors, and has received regulatory approval for obesity management and cardiovascular risk reduction in adults. A central focus is the formulation's strict administration requirements, which are necessary to optimize absorption and bioavailability. The article emphasizes the importance of person-centered consultations between healthcare professionals and patients prior to treatment initiation, covering realistic expectations, adherence strategies, and adverse event management. Key limitations include that this is a guidance/review article rather than a primary clinical trial, meaning its conclusions reflect the authors' synthesis and interpretation of existing evidence rather than new experimental data. It does not establish independent causal efficacy and is subject to potential expert bias.
Postgraduate medicine · Jun 2026DOI ↗ Review
This narrative review examines the potential ocular effects of geroprotective agents — pharmacologic compounds studied for longevity and systemic aging benefits — with a focus on their relevance to age-related eye diseases including age-related macular degeneration (AMD), diabetic retinopathy (DR), retinal vein occlusion (RVO), and glaucoma. The authors argue that shared mechanisms of neurodegeneration, microvascular injury, and chronic inflammation underlie both systemic aging and major retinal diseases, making geroprotectors a pharmacologically relevant class for ophthalmic consideration. The review covers a broad range of agents: GLP-1 receptor agonists, metformin, SGLT-2 inhibitors, statins, cannabinoids, calcium channel blockers, spermidine, taurine, NAD+ precursors, rapamycin, and mifepristone. The authors note that GLP-1 receptor agonists have been associated with potential glaucoma risk reduction but also with unconfirmed reports of nonarteritic anterior ischemic optic neuropathy. The review acknowledges that ocular effects of these agents are incompletely characterized, variably reported, and sometimes controversial. Key limitations include reliance on heterogeneous observational and preclinical data, absence of dedicated ophthalmic clinical trials, and potential confounding in real-world studies. The authors aim to support clinical awareness and identify gaps for future investigation.
Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · Jun 2026DOI ↗ Review
This narrative review proposes a novel conceptual framework for integrating GLP-1 receptor agonists (GLP-1 RAs) into bariatric surgical care, drawing an analogy from oncology's neoadjuvant and adjuvant treatment models. The authors suggest that GLP-1 RAs used before surgery ("neoadjuvant") could reduce perioperative risk—particularly in super-obese patients—by promoting early weight loss and improving dyslipidemia. Used after surgery ("adjuvant"), GLP-1 RAs may address weight regain and sustain metabolic improvements in patients with suboptimal surgical outcomes. The review synthesizes findings from prospective trials, retrospective analyses, and meta-analyses, noting that preoperative GLP-1 RA use appears generally safe but requires monitoring for metabolic adaptation and a potential "ceiling effect" on postoperative results. The authors introduce a proposed "perioperative management ladder" as a structured decision-making tool. Importantly, the framework is described as primarily hypothesis-generating and intended to inform the design of future randomized controlled trials. Key limitations include the review's narrative (non-systematic) methodology, reliance on heterogeneous primary studies, and the absence of original data.
Current obesity reports · Jun 2026DOI ↗ Review
This systematic review examined existing evidence on the use of second-generation incretin analogs — specifically semaglutide (a GLP-1 receptor agonist) and tirzepatide (a dual GLP-1/GIP receptor agonist) — in adults with type 1 diabetes (T1D) or latent autoimmune diabetes in adults (LADA). Researchers screened 3,053 records from six major databases and ClinicalTrials.gov, ultimately identifying 11 eligible publications. These comprised two systematic reviews, one post hoc subgroup analysis, six narrative or consensus reviews, and two LADA case reports. Three key themes emerged from the synthesis: (1) LADA is frequently misdiagnosed or diagnosis is delayed due to its heterogeneous presentation; (2) both tirzepatide and semaglutide show potential benefits in LADA and in certain T1D subtypes, particularly in individuals retaining residual beta-cell function; and (3) existing clinical management frameworks may guide practice while robust trial data are awaited. The authors concluded that current evidence is promising but moderate in quality, and that well-designed, adequately powered randomized controlled trials in clearly defined LADA and T1D populations are needed to establish long-term efficacy and safety. Notable limitations include the small number of eligible studies, the predominance of review-level and narrative publications, and only two primary patient-level reports.
Journal of the American Association of Nurse Practitioners · Jun 2026DOI ↗ Review
This plain-language review provides an educational overview of survodutide, an investigational medication being studied for the treatment of obesity and metabolic dysfunction-associated steatohepatitis (MASH). The review explains how survodutide works mechanistically and summarizes findings from clinical trials, including key health outcomes and reported side effects observed in trial participants. The authors contextualize survodutide within the broader landscape of obesity and MASH as linked metabolic diseases, noting that both conditions involve dysregulation of energy use and storage, and that they frequently co-occur with other metabolic health conditions. Standard-of-care recommendations such as dietary changes and physical activity are acknowledged, alongside pharmacological and surgical interventions. As a review article rather than an original trial, this paper does not generate new primary data; its conclusions are derived from synthesizing existing clinical trial results. Limitations include the non-approved status of survodutide, the inherent scope constraints of a plain-language review format, and the potential for selective reporting of trial findings. The evidence supporting survodutide's effects ultimately depends on the quality and size of the underlying clinical trials referenced, which are not individually appraised within this summary piece.
Therapeutic advances in gastroenterology · Jun 2026DOI ↗ Review
This narrative review examines the continued clinical relevance of dulaglutide, a once-weekly GLP-1 receptor agonist, in the treatment of type 2 diabetes (T2D) amid growing adoption of newer incretin-based therapies such as semaglutide and tirzepatide. The authors synthesize evidence from major cardiovascular outcome trials, including the REWIND trial—which they highlight as the only GLP-1 receptor agonist trial to demonstrate a statistically significant reduction in major adverse cardiovascular events (MACE) in a predominantly primary prevention population over more than five years—and the SURPASS-CVOT, which established tirzepatide's non-inferiority to dulaglutide for cardiovascular outcomes. The review acknowledges that semaglutide and tirzepatide show superior HbA1c reduction and weight loss compared to dulaglutide, but argues that dulaglutide's fixed-dose, no-titration regimen, established cardiovascular safety profile, real-world tolerability, and lower cost support its continued use—particularly in low- and middle-income countries. Limitations include the narrative (non-systematic) review design, which is susceptible to selection bias, and the lack of head-to-head cardiovascular outcome trials directly comparing dulaglutide to semaglutide or tirzepatide.
Diabetology international · Jun 2026DOI ↗ Review
This review paper examines MOTS-c, a mitochondrial-derived microprotein (mitokine) encoded within the 12S rRNA gene, and its potential role in inflammatory lung diseases. The authors synthesize available experimental and clinical literature to explore how MOTS-c influences metabolic homeostasis, oxidative stress, inflammation, autophagy, cell death pathways (including apoptosis, ferroptosis, and pyroptosis), mitochondrial dysfunction, and immune responses. Key findings reported across the reviewed studies include: reduced circulating MOTS-c levels in various forms of acute respiratory distress; attenuation of lung injury following exogenous MOTS-c administration in preclinical models; a partial mechanistic link between remote ischemic preconditioning and MOTS-c release; decreased MOTS-c concentrations in chronic conditions such as COPD, obstructive sleep apnea, and asthma; and preliminary observations of elevated MOTS-c in lung cancer, tentatively attributed to NRF2-mediated antioxidant responses. The authors conclude that MOTS-c holds promise as both a biomarker and therapeutic candidate in respiratory medicine, while acknowledging that current evidence is largely preclinical and that well-designed translational and multicenter clinical trials are needed to confirm any clinical utility. Limitations include the heterogeneity of reviewed study designs and the early-stage, preliminary nature of much of the evidence.
Journal of translational medicine · Jun 2026DOI ↗ Review
This paper is a commentary/review published in Cell Host & Microbe that discusses the expanding role of the gut microbiome in mediating the effects of glucagon-like peptide 1 (GLP-1) receptor agonists. The authors highlight findings from a study by Bian et al., which investigates how the gut microbiome may be involved in the psychological effects of GLP-1 receptor agonist drugs. The commentary contextualizes these findings within the broader landscape of GLP-1 pharmacology, noting that there is substantial evidence for the wide-ranging health benefits of GLP-1 receptor agonists. The paper underscores the concept of drug-microbe-host interactions, suggesting that the therapeutic and psychological effects of GLP-1 receptor agonists may not be solely attributable to direct drug action but may also involve modulation of the gut microbiome. Limitations include the nature of the article as a secondary commentary rather than primary research, meaning it does not present original experimental data. Its conclusions are largely interpretive, and the strength of any causal claims about the microbiome's role depends on the primary studies it references.
Cell host & microbe · Jun 2026DOI ↗ Review
This commentary examines the Institute for Clinical and Economic Review (ICER) report on GLP-1 receptor agonists (GLP-1 RAs) — specifically semaglutide and tirzepatide — for obesity management, evaluating both their clinical value and the challenges surrounding their financing. The authors note that while these agents demonstrate meaningful weight loss and cardiometabolic benefits and were deemed cost-effective versus lifestyle modification alone by ICER, even modest real-world uptake surpasses ICER's annual budget impact threshold, raising access concerns. The commentary highlights that real-world persistence with these medications is notably lower than in clinical trials, leading to frequent weight regain upon discontinuation and limiting anticipated long-term medical cost offsets. Evidence on medical spending is described as mixed: cost-offset signals appear primarily in patients with both obesity and diabetes using high-potency injectable agents, while obesity-only populations may see spending increases. To address these tensions, the authors recommend pairing drug coverage with lifestyle management programs, avoiding arbitrary treatment duration limits, applying targeted prior authorization, and exploring innovative payment models. Key limitations include the commentary format, reliance on heterogeneous real-world data, and lack of primary data collection.
Journal of managed care & specialty pharmacy · Jun 2026DOI ↗ Review
This review examines the rationale and emerging evidence for combining Thymosin α1 (Tα1) — a naturally occurring, pleiotropic immunomodulatory peptide — with immune checkpoint inhibitors (ICIs) in the treatment of solid tumors. The authors first outline the biological characteristics of Tα1, highlighting its dual role in enhancing immune competence (e.g., promoting T-cell maturation and activation) while simultaneously regulating excessive immune responses. They then synthesize preclinical and clinical evidence suggesting that Tα1 may address key limitations of ICI monotherapy, including tumor heterogeneity, immunosuppressive tumor microenvironments, and immune-related adverse events (irAEs). The review argues that Tα1 can synergistically remodel the tumor immune microenvironment when combined with ICIs, potentially improving overall response rates. Preliminary clinical findings cited in the review indicate promising efficacy and manageable safety profiles for the combination. The authors acknowledge that the current evidence base relies heavily on early-phase or smaller studies and explicitly call for large-scale, long-term clinical trials to validate sustained benefits. As a narrative review, it does not generate new primary data, and conclusions are limited by the quality and scale of the underlying studies reviewed.
Frontiers in immunology · May 2026DOI ↗ Review
This review examines what happens to body weight after patients stop taking glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and newer dual/triple co-agonists used for obesity treatment. The authors note that these medications can produce mean weight losses of 10–30%, far exceeding what is typically achievable through lifestyle changes alone. However, the review highlights that real-world data suggest up to 65% of patients discontinue GLP-1 RAs within one year of starting treatment, and randomized controlled trial data indicate that approximately two-thirds of lost weight is regained within a year of stopping the medication. The review explores the physiological, behavioral, and environmental mechanisms that drive this weight regain once pharmacological appetite suppression is removed. The authors conclude that sustaining weight loss after discontinuation will require integrated, patient-centered approaches that combine ongoing lifestyle interventions, behavioral support, and system-level strategies. As a review article, it synthesizes existing evidence but does not generate new primary data, and its conclusions are limited by the quality and scope of the studies it draws upon.
EClinicalMedicine · May 2026DOI ↗ Review
This review synthesizes evidence from randomized controlled trials and high-quality meta-analyses on approved and investigational obesity medications, examining their effects beyond weight loss alone. Medications reviewed include phentermine-topiramate, naltrexone-bupropion, GLP-1 receptor agonists (liraglutide, semaglutide), and newer multiagonist agents (tirzepatide, survodutide, mazdutide, retatrutide, cagrilintide-semaglutide, and amycretin). The authors evaluated impacts across a broad range of obesity-related comorbidities, including type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, chronic kidney disease, heart failure, cardiovascular disease, obstructive sleep apnea, polycystic ovary syndrome, osteoarthritis, muscle mass, depression, quality of life, food cravings, binge-eating disorders, substance use disorders, and neurodegenerative diseases. The review concludes that GLP-1-based and multiagonist therapies demonstrate beneficial effects across these conditions. Notably, the authors report that while many benefits appear to be mediated through weight reduction, accumulating evidence suggests weight loss-independent mechanisms, particularly for GLP-1 receptor agonist-based therapies. Key limitations include its reliance on synthesized rather than primary data and variability in evidence quality across the individual conditions reviewed.
The lancet. Diabetes & endocrinology · May 2026DOI ↗ Review
This narrative review examines the role of lifestyle interventions before, during, and after treatment with second-generation obesity management medications (OMMs), specifically semaglutide and tirzepatide. The authors note that these agents have demonstrated weight losses of approximately 15–20% in recent trials, prompting a reconsideration of how lifestyle programs should be integrated into obesity care. The review identifies several emerging concerns in the literature, including lean mass loss, nutritional deficiencies, gastrointestinal side effects, and significant weight regain following medication discontinuation. The authors argue that lifestyle modification remains the foundation of obesity treatment but that the focus may need to shift from weight reduction toward broader health promotion in the context of highly effective pharmacotherapy. Key lifestyle strategies discussed include protein intake and physical activity to preserve muscle mass, and dietary approaches to manage gastrointestinal side effects. The review also explores pre-treatment lifestyle programs as potential prerequisites for pharmacotherapy while cautioning that such requirements could limit access and reinforce weight stigma. Limitations include the narrative (non-systematic) design, lack of primary data, and the rapidly evolving evidence base. The authors conclude that optimal timing, frequency, and content of lifestyle interventions alongside OMMs remain unclear and warrant further research.
Current atherosclerosis reports · May 2026DOI ↗ Review
This review article argues that GLP-1 receptor agonists (GLP-1 RAs) — such as semaglutide and tirzepatide — should be understood as catalysts for, rather than replacements of, lifestyle intervention in cardiometabolic care. The authors propose the guiding principle "lifestyle first and lifestyle always, but not lifestyle only," acknowledging that GLP-1 RAs have produced meaningful clinical benefits including substantial weight loss, improved glycemic control, and reduced cardiovascular and renal risk. However, the authors contend that pharmacotherapy alone cannot address the full spectrum of cardiometabolic risk drivers, including sarcopenia, physical deconditioning, poor sleep, psychological stress, and social determinants of health. The article highlights that discontinuation of GLP-1 RAs without structured lifestyle support is commonly associated with weight regain. Key lifestyle pillars emphasized include high-quality nutrition, regular physical activity (including resistance training), restorative sleep, stress management, and social connectedness. The authors advocate for integrated, interprofessional care models combining pharmacologic and lifestyle strategies, supported by systemic and policy-level change. As a narrative review, the paper does not present original data, conduct a systematic literature search, or include a meta-analysis, which limits the directness of its evidentiary contribution.
American journal of lifestyle medicine · May 2026DOI ↗ Review
This clinical review synthesizes current evidence on glucagon-like peptide-1 receptor agonists (GLP-1 RAs), a drug class increasingly used to manage type 2 diabetes, obesity, and expanding metabolic and cardiorenal conditions. The authors describe the physiological mechanisms underlying GLP-1 RA action, survey established and emerging clinical indications, and outline practical safety considerations relevant to growing use in younger, healthier, and more diverse patient populations. A central focus is the management of adverse effects—particularly gastrointestinal intolerance—for which the authors propose a structured algorithm to guide early symptom management in clinical practice. The review also addresses communication strategies intended to support shared decision-making, reduce weight-related stigma, and align therapy with individual patient goals and values. As a narrative review without original data collection, the paper does not generate new clinical outcome data and is subject to the selection biases inherent to non-systematic literature reviews. Nonetheless, it offers a clinically oriented framework intended to help practitioners translate evolving GLP-1 RA evidence into individualized, patient-centered care. No external funding was reported.
EClinicalMedicine · May 2026DOI ↗ Review
This systematic review evaluated the clinical trial evidence base for pharmacological treatments of Hypoactive Sexual Desire Disorder (HSDD) in adult women by systematically searching ClinicalTrials.gov in accordance with PRISMA 2020 guidelines. Nine completed interventional clinical trials met the inclusion criteria, most of which were Phase II or Phase III randomized, double-blind, placebo-controlled studies enrolling primarily premenopausal women with acquired, generalized HSDD. The most extensively studied agents were flibanserin and bremelanotide, both of which target central nervous system pathways involved in sexual desire. Efficacy was most commonly assessed using validated patient-reported outcome tools such as the Female Sexual Function Index desire domain and the Female Sexual Distress Scale. The review found notable heterogeneity across trials in endpoint designation, reporting completeness, and safety data presentation, which limited cross-trial comparisons. Adverse events generally reflected the pharmacological mechanisms of the agents studied. The authors concluded that while progress has been made, significant gaps remain in the pharmacological treatment landscape for HSDD, and called for more standardized trial methodologies and comprehensive outcome reporting to strengthen the overall evidence base. A key limitation is that findings were synthesized descriptively without pooled quantitative (meta-analytic) analysis.
Frontiers in medicine · May 2026DOI ↗ Review
This systematic review examined the clinical outcomes of GLP-1 receptor agonists (GLP-1 RAs) and dual GIP/GLP-1 receptor agonists in children and adolescents (aged 6–19 years) with overweight or obesity, with or without type 2 diabetes. Researchers searched PubMed, Scopus, and ClinicalTrials.gov following PRISMA 2020 guidelines, ultimately analyzing 15 studies (12 interventional, 3 observational) comprising 1,448 participants across six agents: liraglutide, exenatide, semaglutide, dulaglutide, tirzepatide, and lixisenatide. Study durations ranged from 6 to 68 weeks. The review found that BMI reductions varied across agents and study designs, with semaglutide trials reporting reductions of up to –16.1%. A key finding was the substantial heterogeneity in how concomitant lifestyle interventions were reported—ranging from general dietary advice to structured multidisciplinary programs—making it impossible to isolate the independent contributions of pharmacological versus behavioral components. The authors conclude that while GLP-1 RAs appear to be a promising therapeutic option in this population, the evidence base is limited by inconsistent lifestyle co-intervention reporting. They call for standardized reporting frameworks (e.g., TIDieR), validated behavioral measures, and factorial or stratified study designs to disentangle drug and lifestyle effects in future pediatric trials.
Nutrients · May 2026DOI ↗