GLP-1 receptor agonist liraglutide facilitates rotator cuff healing by reducing tendon cell inflammation and endoplasmic reticulum stress through the GLP-1R-AMPK/SIRT1 pathway.

Individuals with type 2 diabetes mellitus (T2DM) are at an increased risk of developing epilepsy, particularly in later life. While preclinical studies suggest neuroprotective properties of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), real-world comparative effectiveness data remain limited. We aimed to evaluate whether GLP-1 RA use is associated with a lower risk of incident epilepsy compared with dipeptidyl peptidase-4 inhibitor (DPP-4i) use in adults with T2DM. We conducted a retrospective cohort study using the TriNetX network from 2015 to 2023, including adults aged 18 years or older with T2DM who were new users of either GLP-1 RAs or DPP-4is. Patients with a previous diagnosis of epilepsy or seizure, or those using antiepileptic drugs, were excluded. The primary outcome was incident epilepsy, identified using ICD-10-CM codes. Propensity score matching (1:1) was performed based on demographics, socioeconomic status, body mass index, comorbidities, and baseline medications. Cox proportional hazard models estimated hazard ratios (HRs) with 95% CIs. We also conducted prespecified subgroup and sensitivity analyses to assess the robustness of the findings. After matching, 452,766 patients were included (226,383 in each group; mean age 60.5 years; 47.1% female). During follow-up, 1,670 individuals in the GLP-1 RA group and 1,886 in the DPP-4i group developed epilepsy, corresponding to cumulative incidences of 2.35% vs 2.41%. GLP-1 RA use was associated with a significantly lower risk of epilepsy (HR 0.84, 95% CI 0.78-0.90), with protective associations evident at 1 year (HR 0.71, 95% CI 0.62-0.80), 3 years (HR 0.81, 95% CI 0.74-0.88), and 5 years (HR 0.82, 95% CI 0.76-0.88). Among individual agents, semaglutide showed the strongest association (HR 0.68, 95% CI 0.60-0.77). The results were consistent across major subgroups, including both age and sex. Sensitivity analyses excluding patients with overlapping or switching exposure yielded similar findings (HR 0.71, 95% CI 0.64-0.78). GLP-1 RA therapy was associated with a significantly lower epilepsy risk compared with DPP-4i use in adults with T2DM. These results support the hypothesis that GLP-1 RAs may exert neurologic benefits beyond glycemic control. Limitations include the observational design and potential residual confounding. This study provides Class III evidence that the use of GLP-1 RAs in people with T2DM results in a lower risk of developing epilepsy compared with those treated with DPP-4i.

The incidence and prevalence of both cardiac and renal disease in Germany are steadily rising. Heart disease is the most common cause of death, especially among people with chronic kidney disease. Impaired kidney function increases the risk of cardiovascular events, and vice versa. This narrative review is based on pertinent publications retrieved by a literature search up to the year 2025, with particular attention to the guidelines of the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF) and the European Society of Cardiology (ESC). Supplementary searches were conducted on individual aspects of the epidemiology, diagnosis, and treatment of heart and kidney disease. The heart and the kidneys are closely pathophysiologically linked. Both can be damaged by shared vascular risk factors, including diabetes mellitus, arterial hypertension, and chronic inflammation. These shared mechanisms give rise to a continuum of diseases. Multiple RCTs have shown in recent years that the morbidity and mortality of patients with heart and kidney diseases can be significantly lowered by treatment not only with ACE inhibitors, but also with sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 receptor agonists (GLP1-RA), and nonsteroidal mineralocorticoid receptor antagonists (nsMRA). Absolute risk reductions in the range of 1.8% to 6.7% have been found to be achievable for most of the combined endpoints studied, depending on the particular active substance used. Heart and kidney diseases often arise together and can be treated with new pharmacotherapeutic strategies. Open questions remain concerning the potential synergistic effects of the drugs mentioned above, the suitable management of polypharmacy, and the enabling of cost-effective care.

Analog of prolactin-releasing peptide reduces body weight primarily through sustained fatty acid oxidation rather than hypophagia.

Sexual dysfunction (SD) is a frequent and underrecognized complication of obesity, mediated by a complex interplay of hormonal, vascular, metabolic, and psychosocial pathways. Despite the established link between weight reduction and improved sexual health, the specific effects of new pharmacological weight-loss therapies on sexual function remain underexplored. To critically evaluate the recent evidence on the impact of weight-loss medications on sexual function, synthesizing clinical outcomes, mechanistic insights, and identifying critical research gaps. We conducted an update and comprehensive narrative review using PubMed, Scopus and Embase databases. A systematic search strategy employed predefined terms related to obesity, SD, and pharmacotherapy. Eligible studies were those reporting sexual outcomes using validated instruments [eg, Female Sexual Function Index (FSFI), International Index of Erectile Function (IIEF)] or relevant clinical reports. GLP-1 receptor agonists show promising results in men, improving erectile function, testosterone levels, and sperm parameters. In contrast, direct evidence in women remains limited. Tirzepatide achieves unprecedented weight loss, but case reports suggest potential sexual side effects. Naltrexone/bupropion may benefit sexual desire through mood improvement, while phentermine/topiramate primarily enhances psychological well-being. Setmelanotide demonstrates the direct involvement of the melanocortin pathway in sexual function. Across all drug classes, sexual endpoints were typically secondary outcomes in clinical trials. Pharmacological weight-loss therapies influence sexual health through multiple direct and indirect pathways. However, current evidence is inconsistent, and sex-specific data are scarce. Future clinical trials should systematically include validated sexual function measures as primary endpoints and stratify results by sex and comorbidities to better guide clinical practice in sexual medicine.

Impact of GLP-1 analogues on immune-mediated inflammatory diseases: A systematic review.

Overscreening of patients on glucagon-like peptide-1 receptor agonists: A second "epidemic" of thyroid cancer overdiagnosis?

Glucagon-like peptide-1 receptor (GLP-1R) agonists prevent tributyltin-induced muscle atrophy/wasting via restoring GLP-1R signaling in vitro and in mice.

Certain antidiabetic agents may prevent dementia in patients with type 2 diabetes mellitus (T2DM). The purpose of this study is to elucidate the relative effect of antidiabetic agents on reducing dementia risk in patients with T2DM. PubMed, Cochrane Library and Igaku Chuo Zasshi-Web from inception to 31 December 2023 were searched. Trials reported in English or Japanese language that assessed the effects of glucose-lowering drugs on dementia were selected. Overall, 67 trials (4 088 683 individuals) assessing nine antidiabetic agent classes were included. Studies comprised monotherapies versus control (no use of antidiabetic agents or placebo) (three trials), monotherapies versus add-on therapies (one trial) and real-world database studies (63 trials). The analysis showed that the risk of dementia decreased with sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1-RA), thiazolidinediones (TZD) and dipeptidyl peptidase-4 inhibitors (DPP4i) compared with the reference (placebo, no use of antidiabetic agents or other antidiabetic agents). Conversely, insulin was associated with an increased risk of dementia, whereas no significant association was found with the use of metformin, sulfonylureas, glinides and α-glucosidase inhibitors. Analyses of treatment rankings further revealed the relative effect on reducing dementia risk in the following order: SGLT2i > GLP1-RA > TZD > DPP4i; insulin ranked the lowest. The most effective antidiabetic agent in reducing dementia risk in T2DM is SGLT2i, followed by GLP1-RA, TZD and DPP4i, whereas insulin is associated with an elevated risk of dementia.

Understanding the real-world impact of treatment with empagliflozin and glucagon-like peptide-1 receptor agonists (GLP-1RA) on healthcare resource utilization (HCRU) and costs could help inform clinical decision-making and healthcare policy. We conducted a comparative-effectiveness cohort study comparing HCRU and costs following empagliflozin versus GLP-1RA treatment in adults with type 2 diabetes (≥18 years) using US Medicare and commercial claims (08/2014-09/2019). We estimated rate ratios (RR) for HCRU outcomes using zero-inflated negative binomial regression and cost differences per member per year (PMPY) using gamma regression after adjusting for 143 baseline covariates via propensity score matching. We identified 146,341 matched pairs across all databases. After matching, the rates of hospital days, hospitalizations, emergency department (ED) visits, and physician office visits were similar between treatments. Empagliflozin had lower rates of dispensed medication classes versus GLP-1RA across most databases (RRs ranged from 0.91 to 0.95, RDs from -1246 to -709 per 1000 PY, reflecting varying degrees of precision). Total costs of care were lower with empagliflozin versus GLP-1RA. PMPY ratios ranged from 0.93 to 0.97 and differences from -$1425 to -$847. Inpatient and outpatient costs were comparable between treatments. Empagliflozin had lower pharmacy costs than GLP-1RA, mainly driven by glucose-lowering medications (PMPY ratios ranging from 0.91 to 0.95; PMPY differences from -$799 to -$441). Among adults with diabetes, empagliflozin was associated with similar rates of inpatient days, hospitalizations, ED, and office visits, with lower dispensed medication rates compared with GLP-1RA. Empagliflozin initiators incurred lower total costs, driven by lower glucose-lowering medication costs.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) effectively reduce hypoglycemia and offer additional clinical benefits such as weight loss. However, their high costs impose a significant economic burden on both patients and payers. Health care expenditures associated with GLP-1 RA use have not been adequately examined in previous studies. To examine the excess expenditures (total, payer, and out-of-pocket) associated with GLP-1 RA use compared with nonuse among adults with diabetes in the United States. The study design was cross-sectional using data on adults (aged ≥18years) with diabetes from multiple years (2016, 2018, and 2020) of the Medical Expenditure Panel Survey. Any GLP-1 RA use was derived from prescription medication files. Dependent variables included total, payer, and out-of-pocket health care expenditures. Excess expenditures associated with GLP-1 RAs were estimated using a multivariable generalized linear model (GLM) with gamma distribution and log link. The model adjusted for age, sex, race and ethnicity, social determinants of health, obesity, physical activity, and comorbid conditions. The study sample consisted of 7,670 adults with diabetes, representing approximately 28.6 million individuals in the United States. Overall, 7.5% of adults with diabetes used GLP-1 RAs, with rates increasing from 4.3% in 2016 to 10.6% in 2020. GLP-1 RA users had higher total ($22,029 vs $15,165, P < 0.001), payer ($20,023 vs $13,758, P < 0.001), and out-of-pocket ($2,006 vs $1,407, P < 0.001) expenditures compared with nonusers. Multivariable GLMs indicated that GLP-1 RA users incurred an adjusted excess of $5,417 (P < 0.001), $4,764 (P < 0.001), and $436 (P = 0.001) for total, payer, and out-of-pocket expenditures, respectively. One in 13 adults used GLP-1 RAs. GLP-1 RA users had greater overall, third-party, and out-of-pocket expenditures. These findings underscore the growing economic impact of GLP-1 RA use and highlight the importance of developing strategies that balance the proven clinical advantages of GLP-1 RAs against their financial burden.

Bipolar disorder (BD) is a chronic and disabling psychiatric illness characterized by complex pathophysiological mechanisms. Traditional treatments often fail to address these multidimensional processes, highlighting the need for novel therapeutic strategies. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used for metabolic disorders, have emerged as promising candidates for a range of neuropsychiatric conditions due to their broad neurobiological effects. This narrative review synthesizes preclinical, clinical, and real-world evidence evaluating the therapeutic potential of GLP-1RAs in BD. These agents modulate neurotransmission, reduce neuroinflammation and oxidative stress, enhance mitochondrial and neurotrophic function, and improve insulin sensitivity and hypothalamic-pituitary-adrenal (HPA) axis regulation. These mechanisms are implicated in the neurobiology of BD, and preliminary findings suggest benefits across core psychopathological domains and common comorbidities, including depression, anxiety, mania, cognitive dysfunction, weight gain, and substance use disorders. While human data-particularly in BD populations-remain limited, evidence points to potential adjunctive benefits, especially in individuals with metabolic or cognitive vulnerabilities. Given their pleiotropic actions and established safety profile, GLP-1RAs represent compelling candidates for drug repurposing in BD. Well-powered, controlled trials are needed to confirm efficacy and safety, identify optimal subgroups, and evaluate long-term outcomes.

Are GLP-1 receptor agonists a 'magic bullet' for cancer?

Efficacy of glucagon-like peptide-1 receptor agonists in idiopathic intracranial hypertension: A systematic review and meta-analysis.

Computational modelling the impact of GLP-1 receptor agonists on botulinum toxin A: Evidence for reduced treatment durability across neurologic and aesthetic indications.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for weight management and cardiometabolic health. Common peroneal neuropathy (CPN) associated with rapid weight loss is attributed to adipose tissue reduction and subsequent nerve compression at the fibular head. Cases of "Slimmer's Palsy" have been described in conditions involving rapid weight loss, including anorexia, malignancy, and post-biliary surgery, yet it remains underrecognized as a potential complication of GLP-1RA therapy. This case report describes two nondiabetic patients who developed acute foot drop after losing 14% and 18% of their total body weight over 3-6 months of semaglutide and tirzepatide use, respectively. As use of GLP-1RAs continues to rise, peripheral nerve surgeons should be aware of Slimmer's Palsy as a predictable and treatable complication of rapid weight loss and be prepared to intervene before permanent denervation occurs.

Weight loss from glucagon-like peptide-1 receptor agonists by genetic factors in adults with type 2 diabetes.

FABP4, marker of worse prognosis in cardiovascular disease, induces neutrophil's proatherogenic phenotype which is modulated by semaglutide.

Cardio-renal-metabolic (CRM) syndrome is an emerging nosological entity that reflects the interaction between metabolic risk factors, chronic kidney disease, and cardiovascular disorders. In recent years, it has attracted particular interest, as it appears to be associated with a growing incidence of cardiovascular events, progression of kidney disease, and mortality. The fact that the syndrome has a complex pathophysiology, multiple risk factors, and deleterious effects on different organs and systems necessitates an interdisciplinary approach to its management. Pharmacological agents with positive effects on different components of CRM syndrome, such as sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, have recently been added to our pharmacological arsenal. However, these treatments are underprescribed and used at disproportionately low rates given the significant benefits they offer and the strong level of evidence supporting them, highlighting the need for greater vigilance among physicians regarding the recognition and treatment of the syndrome. This article provides recent data on the definition, pathophysiology, staging, and diagnosis of CRM syndrome and the holistic management of affected patients.

Perivascular adipose tissue in cardiovascular disease: From mechanisms to therapeutic targets.