Orforglipron (OFG), an oral, non-peptide glucagon-like peptide-1 receptor agonist (GLP-1 RAs), showed potential benefits for type 2 diabetes mellitus (T2DM) and obesity. Its dose-response effects on body weight-related parameters and glycemic outcomes remain incompletely analysed. This network meta-analysis aims to address this gap across multiple doses of OFG (3, 12, 24, 36 and 45 mg) in adults with or without T2DM at 12, 26 and 36 weeks.

PRISMA guidelines were followed in our study. Embase, PubMed, Web of Science and Scopus were searched for randomised controlled trials. Random-effects models expressed OFG effects as odds ratios (OR), mean difference (MD) and standardised mean difference (SMD) with 95% confidence intervals (95% CI). RStudio software (version 4.5.1) was used for analysis.

Six RCTs comprising 4878 participants were included. OFG demonstrated reductions in body weight, BMI and waist circumference across all follow-ups. OFG 45 mg dose produced the greatest effects in body weight (SMD: -1.71 kg at 12 weeks, MD: -8.81 kg at 26 weeks and MD: -12.13 kg at 36 weeks vs. placebo). Categorical weight-loss analyses showed that individuals receiving 24-45 mg increased the odds to achieve ≥ 5%, ≥ 10% and ≥ 15% weight loss at 26 weeks. Glycemic outcomes improved across all doses, with the greatest HbA1c reduction at 45 mg (-1.65%; 95% CI -1.98 to -1.32) and greatest fasting glucose improvement at 36 mg dose. Treatment-emergent adverse events increased with dose.

OFG demonstrated improvements in weight-related outcomes and glycemic outcomes. Adverse events increased with dose, consistent with expected class tolerability.

There is a lack of knowledge on the registration of body mass index (BMI) and prevalence of obesity-related complications in the Belgian healthcare system. We therefore evaluated these in Belgians living with overweight or obesity. BMI registration and obesity-related complication prevalences were determined using cross-sectional data from a Belgian general practitioners' morbidity registry (Intego) with 208 891 personal records and from 3605 visitors to an obesity clinic. Two Intego data subsets were used: 53 555 individuals with and 84 017 individuals without registered BMI. Groups were compared using chi-square tests (p-value of < 0.05). For Intego data, BMI was registered in 25.6% of cases. Individuals with registered BMI (mean BMI 27.1 ± 5.5 kg/m²) had a higher prevalence of hypertension (30.1% vs. 17.0%), dyslipidemia (26.9% vs. 14.7%), prediabetes (17.0% vs. 7.9%), type 2 diabetes (12.7% vs. 4.4%) and sleep apnea (3.8% vs. 1.5%) compared to people without registered BMI. People assessed at the obesity clinic (mean BMI 39.0 ± 6.5 kg/m²) had higher prevalences of hypertension (43.1% vs. 37.5%), dyslipidemia (44.4% vs. 32.9%) and sleep apnea (37.9% vs. 5.5%) compared to Intego individuals with BMI ≥ 25 kg/m²(mean BMI 30.3 ± 4.3 kg/m²). BMI is registered only in 25% of patient files in general practice, and people with a registered BMI in general practice have a substantially higher prevalence of the five obesity-related complications than people without registered BMI. When registered, mean BMI is substantially lower than in the obesity clinic, but the prevalence of complications is already substantial, though lower than in the obesity clinic.

Leptospirosis has been infrequently associated with persistent kidney dysfunction fulfilling the criteria for chronic kidney disease (CKD). However, the entity remains poorly characterised. This study aimed to describe the clinical profile, laboratory findings, treatment requirements, and kidney outcomes of patients without recognised CKD risk factors who had persistent kidney dysfunction fulfilling CKD criteria at three-month follow-up after leptospirosis-associated Acute Kidney Injury (AKI).

This descriptive case series was nested within a prospective cohort of hospitalised patients with leptospirosis admitted to a tertiary care hospital in coastal Karnataka, India, between April 2025 and March 2026. Patients with leptospirosis-associated AKI who fulfilled Kidney Disease: Improving Global Outcomes (KDIGO) criteria for CKD at three-month follow-up were included. Leptospirosis was confirmed by immunoglobulin M (IgM) enzyme-linked immunosorbent assay or polymerase chain reaction (PCR). Patients with known CKD or recognised clinical risk factors for CKD, including diabetes mellitus, hypertension, family history of kidney disease, structural renal abnormalities, or other identifiable causes of kidney disease, were excluded. Clinical features, laboratory parameters, treatment details, organ support requirements, and kidney outcomes were recorded.

Among 101 hospitalised patients with leptospirosis, 67 (66.3%) developed AKI. Of these, 7 (10.4%) died in hospital, and 17 (28.3%) of the 60 survivors did not undergo serum creatinine testing at three-month follow-up. Among the remaining 43 evaluable survivors without known CKD or recognised CKD risk factors, 6 (14.0%) fulfilled criteria for CKD at three-month follow-up. All six patients had KDIGO Stage 3 AKI during admission. Admission serum creatinine ranged from 3.19 to 8.63 mg/dL, while peak serum creatinine ranged from 4.92 to 11.84 mg/dL. Jaundice was present in 4/6, 66.7%, of patients, leukocytosis was observed in all patients, and thrombocytopenia was present in all patients. Pulmonary complications were common, with pleural effusion in 4/6, 66.7%, patients, acute respiratory distress syndrome in 1/6, 16.7%, and diffuse alveolar haemorrhage in 1/6, 16.7%. Myocarditis was noted in 2/6, 33.3%, of patients. Three patients required haemodialysis, and three required mechanical ventilation. At discharge, serum creatinine remained elevated in all six patients, ranging from 1.85 to 5.15 mg/dL. At three-month follow-up, estimated glomerular filtration rate (eGFR) ranged from 44 to 59 mL/min/1.73 m²; five patients were classified as CKD Stage 3a and one as CKD Stage 3b.

Severe leptospirosis-associated AKI may be followed by persistent kidney dysfunction at three months despite improvement in serum creatinine from peak values. Persistent creatinine elevation at discharge may be an important clinical warning sign. Patients with severe leptospiral AKI, particularly those with KDIGO Stage 3 AKI, dialysis requirement, persistent discharge creatinine elevation, or multiorgan involvement, may benefit from structured post-discharge kidney follow-up, including eGFR reassessment, urinalysis, proteinuria assessment, blood pressure monitoring, and, where feasible, tubular function testing.

With the advancement of proteomics technologies, an increasing number of studies have begun to examine semaglutide-associated protein expression changes and pathway alterations across different biological contexts. However, existing evidence remains fragmented across different disease backgrounds, sample types, and research platforms, lacking systematic integration.

This review searched PubMed, Embase, and Web of Science for relevant studies published as of April 2026, including population-based, animal, and in vitro model studies that implemented semaglutide interventions and reported proteomic results.

A total of 16 studies were ultimately included, comprising 4 population-based studies and 12 animal and in vitro model studies. The included studies examined both circulating samples and tissue-level specimens, including serum, plasma, adipose tissue, myocardium, aorta, lung, kidney, hippocampus, and skeletal muscle. Common proteomics platforms utilized included SomaScan, TMT-LC-MS/MS, DIA proteomics, phosphorylation proteomics, and mitochondrial proteomics. Multiple studies identified the PPAR signaling pathway, oxidative phosphorylation, and fatty acid metabolism as frequently occurring pathways, while ECM remodeling, complement/inflammatory pathways, and mTORC1 signaling were also observed in some studies. These results suggest that semaglutide is associated with proteomic changes across metabolic, cardiovascular, hepatic, pulmonary, renal, and nervous systems, with recurring signals involving fatty acid metabolism, mitochondrial function, inflammatory protein networks, and extracellular matrix-related pathways.

Overall, proteomic evidence provides a useful molecular framework for describing semaglutide-associated biological responses across multiple tissues. However, existing studies still have limitations such as small sample sizes, high subject heterogeneity, significant differences in proteomic platforms, and limited population studies. Therefore, future research will require larger sample sizes, standardized designs, and multi-omics integration studies to further determine which proteomic signatures are reproducible, biologically meaningful, and clinically translatable.

Cardiovascular risk factors (RFs) are commonly used in clinical practice to predict future adverse cardiovascular outcomes, including acute coronary syndromes (ACS). A recent study reported an association between RFs and plaque vulnerability in patients with ACS.

This study aimed to investigate the association between RFs (modifiable and non-modifiable) and pan-coronary plaque burden, plaque phenotype, and features of vulnerability.

In patients undergoing 3-vessel optical coherence tomography imaging, modifiable (dyslipidemia, hypertension, diabetes mellitus, obesity, smoking) and non-modifiable (age, sex, family history) RFs were recorded. Plaque number, plaque phenotype, and vulnerable features were analyzed.

A total of 534 plaques from 131 patients (36.6% ACS) were analyzed. As the number of RFs increased, the number of plaques (P trend = 0.001) as well as plaques with a vulnerable phenotype (thin-cap fibroatheromas [TCFAs], P trend = 0.001) increased. An increasing number of RFs was also associated with a higher number of vulnerable features (P trend < 0.001), including more thin fibrous caps (P trend = 0.001), lipid-rich plaques (LRPs), macrophages, microvessels, and cholesterol crystals (all P trend ≤ 0.001). In multivariable analyses, only modifiable RF burden was associated with increased pan-coronary vulnerability (incidence rate ratio [IRR]: 1.36; 95% CI: 1.18-1.57; P < 0.001), including a higher prevalence of TCFAs (IRR: 1.48; 95% CI: 1.20-1.83; P < 0.001), LRPs (IRR: 1.35; 95% CI: 1.15-1.59; P < 0.001), and cholesterol crystals (IRR: 1.50; 95% CI: 1.21-1.87; P < 0.001).

As the number of cardiovascular RFs increased, the number of plaques, plaques with a high-risk phenotype, and vulnerable features also increased. Only increasing modifiable RF burden was associated with greater pan-coronary vulnerability, including more TCFAs and LRPs.

ClinicalTrials.gov NCT01110538.

Lipid-based Nanoparticles (LNPs) have emerged as promising carriers for enhancing the efficacy, safety, and patient adherence of antidiabetic therapies. These systems, including Solid Lipid Nanoparticles (SLNs), Nanostructured Lipid Carriers (NLCs), liposomes, and nanoemulsions, exhibit unique physicochemical and pharmacokinetic advantages. Their biocompatibility, ability to protect labile drugs from degradation, and capacity to improve oral bioavailability make them especially valuable for delivering poorly soluble antidiabetic agents. This review comprehensively evaluates various lipid-based platforms, comparing their structural characteristics, drug loading efficiencies, release profiles, and targeting capabilities. SLNs offer excellent stability and controlled release, while NLCs improve drug loading and flexibility. Liposomes provide versatile encapsulation of both hydrophilic and lipophilic drugs, and nanoemulsions are ideal for enhancing rapid absorption. Collectively, these systems outperform conventional formulations by enhancing therapeutic outcomes and reducing systemic side effects. Current challenges, such as large-scale manufacturing and regulatory complexity, are discussed alongside future directions to inform translational research. Lipid-based nanoparticles represent a transformative strategy in the evolution of antidiabetic drug delivery.

Ectopic Cushing syndrome (ECS) is a severe paraneoplastic complication of neuroendocrine neoplasms (NENs), but its association with survival and clinically relevant outcomes remains insufficiently defined in matched real-world cohorts.

To assess the association of code-defined Cushing syndrome compatible with ECS with OS and clinical outcomes in patients with NENs using a large propensity score-matched cohort.

Retrospective cohort study with 1:1 propensity score matching.

Electronic medical records from TriNetX Global Collaborative Network, a federated database aggregating clinical data from international healthcare organizations.

Adult patients (≥18 years) with NEN (n = 105,854), including 265 in the ECS-compatible cohort. After matching, 264 patients in the ECS-compatible cohort were compared with 264 patients without documented Cushing syndrome.

Primary outcome was OS. Secondary outcomes included hospitalization, emergency care use, severe infections, venous thromboembolism, metabolic complications, organ failure, and metastatic progression.

ECS was associated with significantly reduced OS compared with non-ECS patients (8-year survival: 55.3% vs 71.2%; hazard ratio [HR] 1.848 [95% confidence interval 1.348-2.534]; P < 0.001). ECS patients had increased risks of hospitalization, severe infections, venous thromboembolism, and metabolic complications including hypertension, diabetes mellitus, and hypokalemia, as well as organ failure (kidney and liver failure). No significant increase in metastatic progression was observed.

ECS-compatible Cushing syndrome was associated with worse survival and substantially higher morbidity in patients with NENs, mainly reflected by hypercortisolism-related complications rather than tumor progression. Early recognition and treatment of hypercortisolism may be critical to improve outcomes.

Alterations in circulating amino acid profiles have been observed in ischemic stroke patients; however, whether cerebral ischemia disrupts amino acid metabolism within brain tissue and whether this disruption contributes to cellular stress and cerebral injury remain unknown. This hypothesis-testing study investigates disrupted BCAA (branched-chain amino acid) catabolism as a key mechanism of ischemic brain damage and evaluates BCKDK (branched-chain α-keto acid dehydrogenase kinase) as a novel therapeutic target.

Mouse primary cortical neurons subjected to oxygen-glucose deprivation and brain tissue from a mouse acute ischemic stroke model were used as experimental systems. Untargeted metabolomics and metabolic flux analysis were used to characterize BCAA metabolism in both models. In vivo pharmacological inhibition or in vitro knockdown of BCKDK was performed using BT2 treatment or RNA interference. Primary outcome variables included infarct volume, BCKDH (branched-chain α-keto acid dehydrogenase) enzyme activity, neuronal viability, and markers of energy metabolism and glutamate excitotoxicity. Between-group differences were evaluated using 1-way ANOVA; data are presented as mean ± SD with 95% CIs and corresponding P values.

Metabolomics analysis of oxygen-glucose deprivation-exposed primary neurons revealed impaired BCAA catabolism and significant BCAA accumulation compared with normoxic controls. In ischemic mouse brain tissue, BCKDH activity was significantly suppressed, and BCKDK expression was markedly upregulated relative to sham-operated animals. Both pharmacological and genetic suppression of BCKDK substantially reduced cerebral ischemic injury, as evidenced by decreased infarct volume and improved neuronal survival (95% CI and P values per comparison). Mechanistically, ischemia-induced BCKDK expression via HIF-1α (hypoxia-inducible factor 1α)-mediated transcriptional activation, which inhibited BCAA conversion to tricarboxylic acid cycle substrates, thereby potentiating energy deficiency and glutamate excitotoxicity.

These data identify BCKDK as a novel hypoxia-responsive factor whose upregulation drives disrupted BCAA catabolism as a key mechanism of ischemic neuronal injury. BCKDK represents a promising therapeutic target for cerebral ischemia, directly supported by both in vitro and in vivo experimental evidence presented here.

Thyroid disorders (TDs) remain the second-most common endocrine disease after diabetes mellitus worldwide. However, there is a paucity of data on the prevalence and pattern of TDs in northern Nigeria. The study aimed to document the baseline spectrum of thyroid disorders as seen in the endocrinology, diabetes, and metabolism (EDM) outpatient clinic, Department of Internal Medicine of Rasheed Shekoni Federal University Teaching Hospital (RSFUTH), Dutse, over a four-year period.

A retrospective hospital-based descriptive study design was used to review the medical records of all patients seen in the EDM outpatient clinic between September 2020 and August 2024. All endocrinology diagnoses classified according to the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) were recorded. Information on demographic, source of referral, baseline clinical, and biochemical indices were analysed using SPSS version 20, and descriptive statistics were presented.

During the study period, a total of 30 patients' records who met the inclusion criteria were analysed. The mean age was 34.8 ± 10.2. The majority of the patients were female, contributing 76.7%, while males contributed 23.3%. The pattern of thyroid disorders was: Graves's disease among 14 (46.7%) of the patients, followed by toxic multinodular goitre (13%), nodular goitre (13.3%), simple goitre (13.3%), hypothyroidism (6.7%) and subclinical hypothyroidism (6.7%) respectively.

The most common thyroid disorder seen in RSFUTH was hyperthyroidism. Both sexes are affected, but with a female preponderance. There is a need for identifying the underlying risk factors from the identified areas with high burden of the condition, screening for early detection of cases and health education on thyroid disorders for early health-seeking behaviour, to prevent complications.

Chronic pulmonary aspergillosis (CPA) is a recognized complication in patients with pulmonary tuberculosis, particularly in high TB burden regions. Misdiagnosis and inappropriate treatment occur due to overlapping clinicoradiological features, leading to increased morbidity and mortality. Data on CPA occurrence and its association with PTB in tertiary care settings remain limited in resource-constrained countries.

This study enrolled 143 adults from outpatient and inpatient departments. Newly and previously diagnosed PTB patients were included. The CPA diagnosis was based on symptoms lasting over three months, radiological findings, and microbiological/immunological evidence using Aspergillus IgG and BAL galactomannan testing. Data were analyzed using STATA 14.0. Descriptive statistics summarized demographic and clinical data, and comparative analyses between CPA and non-CPA groups used chi-square or Fisher's exact tests for categorical variables and Student's t-test for continuous variables.

CPA was diagnosed in 34.3% (49/143) of PTB patients. The CPA cohort showed male predominance (male-to-female ratio, 4:1), with associations with diabetes mellitus (70.8%, p=0.038) and post-tuberculosis lung disease (61.4%, p=0.040). Radiological features, including cavitation (47.4%, p=0.009), aspergilloma (55.9%, p=0.009), and infiltrates (72.3%, p=0.10) were more frequent in CPA patients. Aspergillus-specific IgG was positive in 69.4% (p<0.001) and BAL galactomannan in 43.9% (p<0.001) of CPA patients.

CPA is prevalent among PTB patients, especially those with TB history and comorbidities like diabetes. Integrated diagnostic approaches, including immunological and antigen testing, are recommended to improve differentiation and management in resource-limited settings.