Review
This commentary argues that the rising popularity of GLP-1 receptor agonists and dual GIP/GLP-1 agonists (such as tirzepatide) for obesity treatment risks overshadowing the need for structural, population-level interventions targeting the food environment. The authors highlight several limitations of a pharmacotherapy-centered approach: high and rising costs (citing recent tirzepatide price increases in the United Kingdom), unequal access across health systems, and the well-documented tendency for weight regain following cessation of these medications. The paper contends that obesity is fundamentally driven by structural factors — including the pervasive availability, marketing, and placement of ultra-processed and high-fat, salt, or sugar (HFSS) foods, alongside limited access to nutritious options. The authors call for complementary population-level policies such as mandatory food reformulation, restrictions on HFSS food marketing, and improved affordability and access to minimally processed foods. The paper acknowledges that medications may provide individual-level benefit but concludes that only comprehensive food-system reform can achieve sustainable reductions in obesity and diet-related disease. As a commentary, it presents no original empirical data, and its conclusions rest on cited evidence rather than new research.
Public health nutrition · Feb 2026DOI ↗ Review
This systematic review, conducted following PRISMA guidelines, synthesizes findings from 68 peer-reviewed studies examining the mechanisms, clinical applications, formulations, and adverse effects of four major sunless tanning agents: dihydroxyacetone (DHA), melanotan (I and II), forskolin, and carotenoids. The authors found that DHA produces skin pigmentation through the Maillard reaction (a non-enzymatic browning of amino acids in the stratum corneum) and has shown additional dermatologic utility in vitiligo and erythropoietic protoporphyria, as well as potential antifungal properties—though concerns about cytotoxicity, genotoxicity, and systemic absorption were noted. Melanotan I and II, which act on melanocortin receptors, were associated with serious adverse effects in unregulated use, including rhabdomyolysis, renal infarction, and priapism. Forskolin was reported to stimulate melanin production independently of melanocortin receptors, with efficacy demonstrated primarily in animal models. Orally ingested carotenoids were found to accumulate in skin and subcutaneous fat, producing a yellow-orange hue. The review acknowledges significant limitations: lack of standardized reporting, heterogeneous outcomes across studies, and insufficient long-term human safety data, particularly for forskolin and carotenoids. The authors conclude that further rigorous clinical research and updated regulatory guidance are needed.
The Journal of clinical and aesthetic dermatology · Feb 2026Source ↗ Review
This narrative review examines complementary biological strategies for managing celiac disease (CeD) beyond a strict gluten-free diet (GFD). The authors synthesize evidence on several therapeutic approaches: (1) enzymatic degradation of immunogenic gluten peptides using bacterial and fungal prolyl endopeptidases (PEPs) and engineered enzyme combinations such as latiglutenase; (2) restoration of intestinal barrier integrity via the zonulin antagonist larazotide acetate; (3) gut microbiota modulation using probiotic strains including Lactobacillus and Bifidobacterium to reduce inflammation and support gliadin breakdown; and (4) plant-derived cysteine proteases from sprouting cereals as gluten detoxification agents. The review also considers enzymatic processing in food production to improve safety and accessibility of gluten-free products. The authors frame these strategies as a multidimensional complement to the GFD, particularly for patients with persistent symptoms or incomplete mucosal recovery following accidental gluten exposure. Limitations inherent to this study type include the absence of a systematic search protocol, potential selection bias in source inclusion, and the inability to draw causal conclusions. Primary clinical trial data across the reviewed interventions vary considerably in quality and scale.
Review
This review paper examines the benefits and harms of GLP-1 receptor agonists (GLP-1 RAs) and dual GLP-1/GIP agonists in the management of obesity. The authors summarize evidence indicating that these drug classes can facilitate significant short-term weight loss and associated improvements in obesity-related conditions, including type 2 diabetes mellitus, cardiovascular disease, and metabolic dysfunction-associated steatotic liver disease. The paper also catalogues a range of adverse effects: common gastrointestinal issues (nausea, vomiting, acute pancreatitis, dehydration, and malnutrition), reduced efficacy of oral contraceptives, allergic reactions, and rarer events such as thyroid cell tumours and non-arteritic anterior ischaemic optic neuropathy. The authors highlight that up to one-third of weight lost may be lean tissue (muscle and bone), discontinuation rates may reach 80% at two years, and subsequent weight regain can account for up to two-thirds of prior loss—often disproportionately as fatty tissue. The paper recommends that GLP-1 RA therapy be initiated alongside supervised exercise and individualised dietary guidance, with ongoing monitoring for cessation, malnutrition, and inappropriate fat regain. A key limitation is that this is a narrative review and does not present original trial data.
Drug and therapeutics bulletin · Jan 2026DOI ↗ Review
This narrative review examines three incretin-based therapies — liraglutide, semaglutide, and tirzepatide — approved for weight management in non-diabetic individuals with obesity. The authors provide background on the physiological roles of the incretin hormones GIP and GLP-1 in the gastrointestinal tract, explaining how pharmacological analogues of these hormones, initially developed for type 2 diabetes, were subsequently found to produce clinically meaningful weight reduction. The review compares the three agents across efficacy, safety, cost-effectiveness, and real-world clinical trends. Lifestyle interventions (dietary modification, physical activity, sleep, and stress management) are discussed as foundational components of obesity management. The authors highlight that all three agents are now regulatory-approved for obesity in non-diabetic patients. As a narrative review, the paper synthesizes existing literature rather than generating new primary data, and is therefore subject to selection bias in the studies chosen. It does not conduct a formal systematic search or meta-analysis, limiting the objectivity of comparisons. No new clinical trial data are presented, and conclusions about relative efficacy and cost-effectiveness are drawn from the authors' interpretation of the existing evidence base.
Rambam Maimonides medical journal · Jan 2026DOI ↗ Review
This review examines the expanding therapeutic applications of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) beyond their original indication of glycemic control in type 2 diabetes. The authors survey clinical trial evidence supporting the use of GLP-1 RAs across several cardiometabolic conditions, including obesity, heart failure with preserved ejection fraction, chronic kidney disease, and metabolic dysfunction-associated steatotic liver disease (MASLD). The review highlights that robust clinical trial data exist for weight loss, cardiovascular outcome improvements, and renal function preservation. The authors also note that additional trials are ongoing to further broaden and strengthen the evidence base. Practical challenges are discussed, including high costs, limited patient access, adherence difficulties, and implementation barriers—especially for indications outside of diabetes. The review identifies emerging innovations, such as oral GLP-1 RA formulations and combination therapies, as potential avenues to improve accessibility and long-term use. The authors conclude that as clinical guidelines continue to evolve, targeted integration of GLP-1 RAs into care pathways may reshape prevention and treatment strategies for complex chronic diseases. As a narrative review, this paper synthesizes existing literature but does not generate new primary data, which limits the directness of its evidence.
Reviews in cardiovascular medicine · Jan 2026DOI ↗ Review
This review examines the potential role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in managing diabetic foot ulcers (DFUs), a serious chronic complication of diabetes associated with high rates of disability, recurrence, and mortality. The authors note that DFU-related mortality is strongly tied to cardiovascular events, suggesting that treatment should extend beyond local wound care to include cardiovascular risk reduction. The review systematically describes personalized application strategies for GLP-1 RAs based on DFU clinical staging, and compares mono-, dual-, and triple-target GLP-1 RA agents in terms of their clinical translational potential and adverse effect profiles specific to DFU patients. Notably, the authors highlight a key tension: while GLP-1 RAs have demonstrated cardiovascular protective effects in outcome trials, their appetite-suppressing and gastric-emptying-delaying properties may worsen malnutrition in DFU patients during acute infection phases. The review synthesizes existing evidence to propose more rational, stage-specific treatment frameworks. As a narrative review, it does not generate new primary data, and its conclusions are limited by the quality and scope of the underlying studies it synthesizes.
Frontiers in endocrinology · Jan 2026DOI ↗ Review
This review synthesizes existing preclinical and emerging translational evidence on Thymosin β4 (Tβ4), a conserved 43-amino-acid peptide, and its N-terminal metabolite Ac-SDKP (N-acetyl-Ser-Asp-Lys-Pro), as potential therapeutic candidates in kidney disease. The authors map the intracellular and extracellular mechanisms of the Tβ4–Ac-SDKP axis, including its roles in actin sequestration, cytoprotection, anti-inflammatory signaling, and antifibrotic actions across both glomerular and tubular compartments. Evidence is evaluated across models of both acute and chronic kidney injury. The review acknowledges contradictory findings regarding fibrosis and proposes conceptual frameworks to explain bidirectional effects and model-dependent mechanisms. Translational considerations discussed include peptide pharmacokinetics, stability challenges, and drug delivery strategies. The authors note that key barriers to clinical translation remain, including the need for validation in additional clinically relevant models, resolution of peptide instability, and comprehensive safety profiling. As a narrative review, this paper does not generate new experimental data, and its conclusions are limited by the quality and heterogeneity of the underlying studies, most of which appear to be animal-based.
Review
This review examines the evolving therapeutic role of amylin, a pancreatic peptide hormone, in managing "diabesity" — the coexistence of diabetes and obesity — over the past five years. The authors describe amylin's physiological mechanisms, including postprandial glucose regulation through delayed gastric emptying and glucagon suppression, as well as appetite control via central nervous system pathways. The review covers preclinical development of long-acting amylin analogs with improved pharmacokinetics and reduced aggregation, which demonstrated significant metabolic benefits in animal models. Clinically, the review highlights pramlintide, a synthetic amylin analog shown to modestly improve glycemic control and promote weight loss in diabetic patients. It also discusses cagrilintide, a newer long-acting analog, which the authors report has produced substantial weight reduction in individuals with obesity. Notably, the review emphasizes that combining amylin analogs with GLP-1 receptor agonists may achieve synergistic weight loss exceeding 15%. Limitations include the inherent constraints of a review design — it does not present new primary data, and the breadth of evidence cited spans preclinical to early clinical stages, meaning conclusions about long-term efficacy and safety remain preliminary.
Journal of obesity & metabolic syndrome · Jan 2026DOI ↗ Review
This commentary is aimed at clinicians and provides practical guidance for counseling patients who are hesitant about starting glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy due to concerns about its perceived "newness" or unproven long-term safety. The paper briefly traces the history of GLP-1, from its discovery in the 1980s through nearly two decades of clinical use, to contextualize these agents as well-established rather than experimental. It distinguishes native GLP-1 from structurally modified agents such as semaglutide and tirzepatide, arguing that modifications prolong drug action without fundamentally changing the hormone's core mechanism. The authors summarize available safety data, noting that known side effects are predominantly mild and transient gastrointestinal in nature, and that there is currently no established evidence linking GLP-1RAs to feared risks such as cancer. The paper includes a practical counseling checklist and sample patient-friendly language intended to support shared decision-making conversations. Key limitations include the absence of original data, lack of systematic literature review methodology, and potential for author bias in evidence selection. Findings and reassurances are the authors' interpretive positions rather than conclusions drawn from a primary study.
American journal of preventive cardiology · Jan 2026DOI ↗ Review
This paper examines the growing use of glucagon-like peptide-1 (GLP-1) receptor agonists — specifically semaglutide and tirzepatide — in the context of obesity management. The authors discuss how these medications have meaningfully shifted the landscape of obesity care, while simultaneously raising important questions about their safety profile, long-term outcomes, and the risks associated with unregulated or compounded versions of these products. The paper highlights the tension between rapidly increasing patient demand and the need for robust clinical oversight. Key concerns addressed include adverse side effects, the consequences of unsupervised use, and the importance of coordinated clinical frameworks to ensure patients access these therapies safely. The authors advocate for structured monitoring systems and regulatory vigilance to keep pace with the surge in prescribing. As a review or commentary piece rather than an original clinical trial, the paper does not generate new primary data; its conclusions are based on synthesis of existing evidence and expert perspective. This limits its ability to independently establish causality or quantify risk with precision, and readers should interpret its claims in that context.
PLoS medicine · Jan 2026DOI ↗ Review
This narrative review examines the problem of lean body mass (LBM) loss associated with weight loss, with particular focus on incretin-based therapies such as GLP-1 receptor agonists (e.g., semaglutide) and dual GIP/GLP-1 receptor agonists (e.g., tirzepatide). The authors queried PubMed, Medline, and Scopus for randomized controlled trials and Phase II/III trials related to obesity, muscle loss, and lean mass preservation, excluding animal studies. The review outlines the physiological mechanisms driving muscle loss during caloric deficit—including reduced anabolic signaling, increased protein catabolism, and hormonal changes—and surveys pharmacological agents under investigation to counteract these effects. Key drug classes discussed include bimagrumab (an activin receptor antagonist targeting the myostatin pathway), tesamorelin (a growth hormone-releasing hormone agonist), and enobosarm (a selective androgen receptor modulator). The authors note that while incretin-based therapies represent a major advance in obesity management, the accompanying loss of muscle mass is a clinically meaningful concern. Most agents targeting LBM preservation are in early research phases. Limitations include reliance on narrative rather than systematic methodology, potential selection bias in study inclusion, and the rapidly evolving evidence base in this area.
Journal of clinical medicine · Jan 2026DOI ↗ Review
This paper examines the ethical dimensions of prescribing semaglutide (marketed as Ozempic, Wegovy, and Rybelsus) to children in the context of its expanding regulatory approvals for paediatric obesity management across several countries, including Germany, the UK, Denmark, and the United Arab Emirates. The authors explore tensions between the potential benefits of semaglutide — such as reducing cardiovascular risk and preventing obesity-related illness in children — and significant concerns including uncertainties about long-term safety, effects on child development, and unanswered efficacy questions in younger populations. The paper focuses particularly on three ethical challenges: access barriers and health equity, the risk of reinforcing weight-based stigma, and the tendency to overlook structural and social determinants of childhood obesity. The authors offer ethical recommendations for clinicians aimed at minimising harm, respecting children's autonomy, and promoting overall health. As an ethics and policy review paper, it does not present original clinical trial data, and its conclusions are based on normative argument and synthesis of existing literature rather than empirical evidence from controlled studies.
Archives of disease in childhood · Jan 2026DOI ↗ Review
This state-of-the-art narrative review examines the potential role of innovative diabetes therapies — specifically incretin-based therapies (GLP-1 receptor agonists), SGLT2 inhibitors, and emerging dual/triple receptor agonists — in modifying the course of diabetic peripheral neuropathy (DPN) and autonomic diabetic neuropathy. The authors synthesize evidence from preclinical models, clinical trials, and real-world observational studies, arguing that GLP-1 RAs and SGLT2 inhibitors may offer neuroprotective benefits beyond their established glucose-lowering effects, potentially through attenuation of inflammation and oxidative stress, improved mitochondrial function, and reduced neuronal damage. The review also highlights novel dual and triple receptor agonists as emerging agents with theoretical synergistic neuroprotective potential via simultaneous activation of multiple metabolic pathways. Limitations inherent to this paper include its narrative (non-systematic) design, which introduces selection bias, and the authors' own acknowledgment that clinical data on newer agents in the context of DN remain limited. The review does not generate new primary data. Overall, it provides a useful conceptual synthesis of an evolving therapeutic landscape but cannot establish causality or definitive efficacy for any agent in DN.
Diabetes therapy : research, treatment and education of diabetes and related disorders · Jan 2026DOI ↗ Review
This narrative review synthesizes mechanistic and clinical trial evidence on incretin-based therapies — GLP-1 receptor agonists (GLP-1RA), DPP-4 inhibitors, and newer dual/triple agonists — for cardiovascular (CV) and renal protection in type 2 diabetes (T2DM) and related conditions. The authors draw on multiple pivotal randomized cardiovascular outcome trials (CVOTs), including SELECT (semaglutide in obesity without diabetes), FLOW (semaglutide in chronic kidney disease), SOUL (oral semaglutide in T2DM with ASCVD/CKD), and SURPASS-CVOT (tirzepatide vs. dulaglutide). Key findings attributed to these trials include reductions in major adverse cardiovascular events (MACE), CV and all-cause mortality, heart-failure hospitalization, and hard kidney endpoints across GLP-1RA programs. A 2019 pooled analysis and a 2025 update reportedly confirm these cardiorenal benefits independent of baseline HbA1c. Mechanistically, the review describes GLP-1R signaling via Gs-cAMP/PKA, β-arrestin, and Gq pathways, linked to anti-inflammatory, natriuretic, and antifibrotic effects. Oral small-molecule GLP-1R agonists (e.g., orforglipron) showed phase 2 efficacy but lacked long-term outcome data at time of publication. As a narrative review, it is subject to selection bias and does not conduct formal meta-analytic pooling.
Diabetes therapy : research, treatment and education of diabetes and related disorders · Jan 2026DOI ↗ Review
This narrative review examines the potential role of therapeutic peptides in orthopaedic care, synthesizing preclinical and mechanistic literature across several peptide classes. The authors categorize peptides by their primary proposed function: wound-healing agents (BPC-157, TB-500, GHK-Cu), growth hormone secretagogues (ipamorelin, CJC-1295, tesamorelin, sermorelin, AOD-9604), recovery-enhancing peptides (epithalon, delta sleep-inducing peptide, pinealon), and neuroactive peptides (selank, semax, dihexa). The review describes how these compounds are theorized to interact with signaling pathways—including PI3K/Akt, mTOR, MAPK, TGF-β, and AMPK—to promote tissue regeneration, resolve inflammation, and support neuromuscular recovery. The authors acknowledge that, while preclinical evidence is promising, robust human clinical trial data are largely absent, representing a significant gap in the literature. Limitations include the review's reliance on animal and in vitro studies, the absence of a systematic search methodology, and the lack of direct clinical evidence supporting efficacy or safety in human orthopaedic populations. The authors call for future controlled trials to validate these mechanistic findings in clinical settings.
Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews · Jan 2026DOI ↗ Review
This perspective article examines retatrutide (LY3437943), a novel triple receptor agonist that simultaneously targets GLP-1, GIP, and glucagon receptors, positioning it as a significant advancement in obesity pharmacotherapy. The authors contextualize retatrutide within the broader evolution of incretin-based therapies, arguing that its multi-hormonal mechanism addresses limitations of existing GLP-1 and dual GIP/GLP-1 agonists. The article highlights Phase 2 trial findings, which reportedly demonstrated weight reductions comparable to bariatric surgery, along with potential benefits for metabolic comorbidities including non-alcoholic steatohepatitis (NASH) and cardiovascular disease. The authors frame retatrutide as a proof-of-concept for rational multi-agonist peptide engineering and advocate for broader scientific engagement, health equity considerations, and proactive policy planning in anticipation of wider clinical adoption. As a perspective/review piece, this paper synthesizes existing evidence rather than presenting original trial data, and does not provide head-to-head comparisons or long-term safety data. Its conclusions are largely interpretive, and the characterization of Phase 2 findings as surgery-comparable warrants cautious interpretation pending Phase 3 results and regulatory review.
Clinical pharmacology in drug development · Jan 2026DOI ↗ Review
This review synthesizes evidence from approximately 108 priority studies—including RCTs, prospective cohorts, and mechanistic reports—identified through a systematic search of PubMed, Scopus, and Web of Science (2000–2025) to reframe heart failure with preserved ejection fraction (HFpEF) as a systemic cardio-metabolic syndrome rather than a purely cardiac condition. The authors argue that visceral adiposity, insulin resistance, chronic inflammation, and mitochondrial dysfunction collectively impair cardiac energetics and drive HFpEF pathophysiology. The review notes that conventional neurohormonal therapies (RAAS inhibitors, beta-blockers) showed neutral outcomes in heterogeneous HFpEF populations, whereas the landmark EMPEROR-Preserved and DELIVER RCTs demonstrated that SGLT-2 inhibitors reduced hospitalizations and cardiovascular events. GLP-1 receptor agonists were also reported to improve symptoms, exercise tolerance, and body weight, further supporting a metabolic-inflammation framework. The authors call for biomarker-driven patient phenotyping, advanced imaging, and adaptive trial designs to enable precision care. Limitations include the inherent heterogeneity of HFpEF populations and the reliance on synthesized rather than primary data, with mechanistic claims drawn partly from preclinical and observational sources.
Review
This narrative review synthesizes existing literature on obesity management strategies, drawing from PubMed, Scopus, ScienceDirect, and Google Scholar. It evaluates the comparative effectiveness, safety, sustainability, and real-world applicability of five broad intervention categories: lifestyle modifications, dietary approaches, behavioral therapy, pharmacotherapy, and bariatric or endoscopic procedures. Key findings reported by the authors include that lifestyle interventions, while foundational, are frequently undermined by physiological adaptations, behavioral challenges, and socioeconomic barriers. Dietary strategies tend to converge in weight-loss outcomes over time, with adherence emerging as the primary differentiator. Pharmacotherapy—particularly incretin-based agents such as GLP-1 receptor agonists and dual GIP/GLP-1 agonists—is highlighted as producing meaningful weight loss and cardiometabolic improvements, though the authors note concerns around cost, tolerability, and the need for continued use. Bariatric surgery is characterized as the most effective long-term option for severe obesity, with endoscopic procedures noted as an expanding alternative. Behavioral and psychological support is identified as a cross-cutting enabler of adherence. The authors conclude that personalized, multidisciplinary care is essential. As a narrative review, this paper does not conduct original data collection or meta-analysis, and findings are subject to selection bias inherent in non-systematic review methodology.
Journal of obesity · Jan 2026DOI ↗ Review
This review examines the evolving landscape of glucagon-like peptide-1 receptor agonist (GLP-1RA) therapies and their role in cardiorenal protection in metabolic diseases, particularly type 2 diabetes (T2D) and obesity. The authors synthesize evidence from clinical and real-world studies demonstrating that GLP-1RAs consistently reduce HbA1c and body weight, and that mounting data support cardiovascular and kidney benefits beyond glycaemic control in high-risk populations. The review highlights that in T2D, GLP-1RAs have been shown to improve hard cardiovascular outcomes and, more recently, kidney outcomes. In individuals with obesity without T2D, semaglutide at a higher dose was reported to reduce body weight by up to 15% and lower major adverse cardiovascular events by approximately 20%. The review also covers next-generation "multi-agonist" molecules combining GLP-1 receptor agonism with activity at GIP, glucagon, and amylin receptors, aiming for complementary or synergistic metabolic effects. Tirzepatide, a dual GLP-1/GIP receptor agonist approved for T2D and obesity, is highlighted as achieving up to 22.5% weight loss in phase 3 trials. Limitations include the inherent constraints of a narrative review: no new primary data are generated, and conclusions depend on the scope and quality of included studies.
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · Jan 2026DOI ↗