Obesity is frequently accompanied by low-grade systemic inflammation and increased cardiovascular risk. We evaluated whether glucagon-like peptide-1 receptor agonist (GLP-1 RA) exposure was associated with improved long-term outcomes among adults with obesity and C-reactive protein (CRP) levels of 3-10 mg/L. Using the TriNetX Global Collaborative Network, adults with body mass index ≥30 kg/m[2] who received a GLP-1 RA were compared with an active-comparator cohort receiving metformin, orlistat, or phentermine without GLP-1 RA exposure. Following 1:1 propensity-score matching, 50,009 patients were included in each cohort and followed for up to 3,650 days. GLP-1 RA exposure was associated with a lower hazard of the primary composite outcome of all-cause mortality, acute myocardial infarction, and ischemic stroke (hazard ratio[HR] 0.799, 95% confidence interval[CI] 0.772-0.825; P<0.001), driven primarily by lower all-cause mortality (HR 0.608, 95% CI 0.578-0.640; P<0.001). Ischemic stroke, arrhythmias, and heart failure with reduced ejection fraction were modestly lower, whereas acute myocardial infarction and incident heart failure with preserved ejection fraction did not differ significantly between cohorts. In conclusion, GLP-1 RA exposure was associated with lower long-term composite clinical events among adults with obesity and CRP levels of 3-10 mg/L, predominantly reflecting lower mortality; prospective studies incorporating longitudinal weight and CRP measurements are needed to evaluate potential mediating mechanisms.

The global prevalence of obesity is rising rapidly. With several antiobesity medications approved and many more in development, understanding their economic value is increasingly important. This study reviews full economic evaluations of approved antiobesity medications to assess cost-effectiveness and inform reimbursement and access decisions. We systematically reviewed full economic evaluations of approved antiobesity medications in adults with overweight or obesity, including tirzepatide, semaglutide, liraglutide, naltrexone/bupropion, orlistat, phentermine and phentermine/topiramate. Ovid MEDLINE, Embase and government websites were searched for studies comparing these medications with standard care or with each other. Methodological quality was assessed using the BMJ checklist and reporting quality using CHEERS 2022. A narrative synthesis was performed, focusing on quality-adjusted life years and incremental cost-effectiveness ratios. The review followed PRISMA guidelines and was registered on PROSPERO (CRD420251139475). Twenty-six studies met inclusion criteria. All were conducted in high or upper-middle-income countries, predominantly from payer perspectives. Results were heterogeneous and sensitive to model assumptions; however, consistent trends emerged. Semaglutide demonstrated variable cost-effectiveness but consistently outperformed liraglutide, which was generally not cost-effective. Tirzepatide produced greater health gains and frequently favourable ICERs, though it often exceeded willingness-to-pay (WTP) thresholds in lower-threshold settings. Among older agents, phentermine/topiramate appeared economically competitive, largely due to lower acquisition costs. The cost-effectiveness of antiobesity medications is highly context-dependent. Semaglutide is generally more cost-effective than liraglutide, while tirzepatide offers greater clinical benefit but may exceed WTP thresholds. Direct comparative economic evidence between newer agents remains limited. Long-term real-world data and clearer distinctions between cost-effectiveness and affordability are needed to inform policy decisions.

Obesity is now recognized as a chronic, multifactorial, and progressive disease as opposed to mere excess of body weight. It significantly increases the risk of type 2 diabetes, cardiovascular disease, metabolic-associated fatty liver disease, and mental health disorders. 2022 data reveal that nearly 3 billion individuals worldwide were living with either obesity or overweight. Pharmacological therapy has evolved remarkably. Earlier medications targeted primarily the brain's monoaminergic pathways but they were withdrawn due to safety concerns. Currently, six medications (Orlistat, Phentermine/Topiramate, Naltrexone/Bupropion, Liraglutide, Semaglutide, and Tirzepatide) are approved by the U.S. Food and Drug Administration for long-term obesity management and among these, glucagon-like peptide receptor agonists have revolutionized the therapy. The emerging pipeline is even more promising. It has new dual and triple combinations such as CagriSema, Survodutide, and Retatrutide for better efficacy and metabolic outcomes, as well as long-acting and oral formulations, which will improve adherence and accessibility. India released its new obesity guideline in January 2025, emphasizing on early pharmacotherapy initiation and the adoption of stage-based obesity classification. Together, these developments signify a transformative era in obesity care where pharmacotherapy is a powerful and evidence-based tool that, in many cases, approaches the efficacy and metabolic benefits traditionally associated with bariatric surgeries.

Obesity is a multifactorial condition that profoundly affects female reproductive health through endocrine, metabolic, and inflammatory mechanisms that disrupt the hypothalamic-pituitary-gonadal (HPG) axis. Women with obesity frequently develop menstrual irregularities, anovulation, amenorrhea, infertility, polycystic ovary syndrome (PCOS), impaired endometrial receptivity, and adverse pregnancy outcomes. Central obesity and insulin resistance contribute to hyperinsulinemia, reduced sex hormone-binding globulin (SHBG) levels, hyperandrogenism, altered gonadotropin secretion, and impaired folliculogenesis, while adipokines such as leptin and chronic inflammation further impair ovarian steroidogenesis and ovulatory function. Obesity-related oxidative stress and lipotoxicity also negatively affect oocyte quality, embryo development, implantation, and assisted reproductive technology outcomes, increasing the risk of gestational diabetes, preeclampsia, miscarriage, and preterm birth. This review evaluates the therapeutic potential of pharmacological weight-loss therapies in obesity-associated female reproductive dysfunction. A comprehensive literature review was conducted using various databases, focusing on anti-obesity pharmacotherapy on obesity, infertility and fertility in reproductive-aged women. Evidence suggests that several FDA-approved and off-label anti-obesity agents, including orlistat, liraglutide, semaglutide, phentermine/topiramate, bupropion/naltrexone, metformin, exenatide, and tirzepatide, may improve reproductive outcomes primarily indirectly through weight reduction and metabolic improvement. GLP-1 receptor agonists, particularly liraglutide, semaglutide, and exenatide, appear especially promising, demonstrating beneficial effects on insulin sensitivity, menstrual regularity, ovulation, androgen levels, and pregnancy rates in women with PCOS. Tirzepatide, a dual GLP-1/GIP receptor agonist, has shown potent weight-loss and metabolic effects with potential indirect fertility benefits. Metformin improves insulin sensitivity and is widely used in PCOS to regulate androgen levels and restore ovulation, although its effects on pregnancy and live birth rates remain controversial. However, evidence for several agents remains limited, and concerns persist regarding reproductive safety during pregnancy. Overall, anti-obesity pharmacotherapy may represent an important adjunctive strategy for improving reproductive and metabolic health in women with obesity, although larger randomized clinical trials are still required.

This study aimed to evaluate the association between tirzepatide use and the risk of carpal tunnel syndrome (CTS) and CTS surgery compared with both glucagon-like peptide-1 receptor agonists (GLP-1RAs) and other anti-obesity medications in individuals who are overweight or obese. We conducted a multicenter retrospective cohort study using the TriNetX US Collaborative Network with a target trial emulation design. Adults aged ≥ 18 years who are overweight or obese and initiated tirzepatide, GLP-1RAs, or other anti-obesity medications (including orlistat or phentermine) between January 2022 and December 2024 were included. Propensity score matching (1:1) was applied to balance demographics, BMI, comorbidities, and socioeconomic variables. Primary outcomes were incident CTS and CTS surgery, with hazard ratios (HRs) and 95% confidence intervals (CIs) estimated. Sensitivity analyses varied lag periods, follow-up durations, analytical frameworks, and matching strategies, while subgroup analyses examined age, sex, race, BMI, and diabetes status. The study complied with the Declaration of Helsinki and received IRB exemption (#11312-E01 and #11212-E02). After matching, well-balanced cohorts were achieved across comparisons. Tirzepatide use was associated with a significantly lower risk of CTS compared with GLP-1RAs (HR 0.82; 95% CI 0.71-0.95), with no significant difference in CTS surgery. In comparison with other anti-obesity medications, tirzepatide was associated with reduced risks of both CTS (HR 0.75; 95% CI 0.65-0.85) and CTS surgery (HR 0.64; 95% CI 0.44-0.94). In conclusion, Tirzepatide use was associated with reduced risks of CTS, particularly when compared with non-GLP-1RA therapies, suggesting potential metabolic and neuroprotective benefits.

Urine drug screening is a valuable diagnostic tool for assessing acute intoxications in the emergency department. Enzyme immunoassay (IA) and immunochromatography (IC) are the two main techniques routinely used due to their rapid turnaround, low cost, and high sensitivity. However, results must be interpreted with caution, as structural cross-reactivity may cause false-positive (FP) findings. We retrospectively analyzed 55 urine samples from emergency patients initially screened for amphetamines by IA and confirmed by gas chromatography-mass spectrometry (GC-MS). Samples containing amphetamine derivatives or potentially cross-reactive substances (tetracaine, trazodone, methylphenidate, ritalinic acid, phentermine, procainamide, ephedrine, bisoprolol, and synthetic cathinones) were subsequently analyzed using an IC assay. Diagnostic performance and cross-reactivity were compared between both screening methods. Of the 55 samples selected by IA, 34 were true positives (TP), 8 true negatives (TN), 2 false negatives (FN), and 11 FP. FP by IA were mainly due to tetracaine, trazodone, phentermine, ephedrine, and procainamide. In comparison, IC yielded 32 TP, 17 TN, 2 FP (phentermine and bisoprolol), and 4 FN. No cross-reactivity with methylphenidate and synthetic cathinones was observed in either technique. IC showed frequent misclassifications between amphetamine and methamphetamine while MDMA detection was more specific. IC is a reliable and rapid alternative for amphetamine screening in the emergency setting, providing improved specificity and fewer false positives than IA. Given its limited discrimination between amphetamine and methamphetamine, IC results should be reported as 'amphetamine derivatives'. These findings highlight assay-dependent cross-reactivity and the importance of understanding methodological limitations for an accurate interpretation.