This review provides a comprehensive examination of the clinical pharmacological mechanisms and broad therapeutic applications of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual receptor agonists targeting both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. GLP-1RAs exert their effects by stimulating insulin secretion, suppressing glucagon release, delaying gastric emptying, and reducing appetite through the activation of the GLP-1 receptor. These agents have demonstrated significant efficacy in the management of type 2 diabetes mellitus (T2DM) and obesity. Moreover, emerging evidence suggests that GLP-1RAs may confer cardiovascular protection, neuroprotective benefits, and positive effects on mental health. Dual GLP-1/GIP receptor agonists, such as tirzepatide, simultaneously activate both receptors, thereby potentiating glycemic control, promoting weight loss, and ameliorating metabolic dysfunction. This review also addresses recent advances in the development of other dual and triple receptor agonists. Distinct from prior reviews that predominantly focus on a single drug class or limited clinical indications, this article systematically contrasts the mechanistic pathways, therapeutic efficacy, and safety profiles of GLP-1RAs versus GLP-1/GIP dual receptor agonists. Notably, it integrates the most current evidence pertaining to novel domains, such as perioperative management, neuropsychiatric outcomes, and the innovation of multi-receptor agonists. This synthesis offers a timely and practical resource to inform clinical precision medicine and to guide future investigative efforts.

Aims. To examine pancreatic volume (PV) changes among patients with different duration of type 2 diabetes and whether pancreatic atrophy was associated with loss of insulin secretory capacity. Methods. This cross-sectional study (203 patients with type 2 diabetes, 93 controls without diabetes) was conducted from January 2016 to December 2017. Patients with type 2 diabetes were divided into 3 groups: recently diagnosed (duration≤2years), midterm (duration 3-9 years), and long term (duration≥10years). All the patients were scanned with upper abdominal computerized tomography; PV was then calculated by an experienced technician. Absolute insulin deficiency was defined as fasting C−peptide<0.9ng/mL. Results. Compared with PV (cm³) in the controls, the mean PV was similar in patients with recently diagnosed type 2 diabetes (68.8 versus 71.0, P=0.56) but significantly reduced in patients with midterm (68.8 versus 60.8, P<0.05) and long-term (68.8 versus 53.1, P<0.001) type 2 diabetes. A similar trend was observed for the PV index (PV adjusted for body surface area and body mass index). Furthermore, rates of pancreatic atrophy and absolute insulin deficiency increased with duration of diabetes. Multiple logistic regression analysis indicated that pancreatic atrophy was associated with higher likelihood of absolute insulin deficiency (oddsratio=4.47, 95%confidenceinterval=1.45‐13.8). Conclusions. PV was reduced in those with midterm and long-term type 2 diabetes compared to individuals without type 2 diabetes. Overall, pancreatic atrophy was associated with the loss of insulin secretory capacity in patients with type 2 diabetes.

Aims. To explore the relationship between monocyte‐to‐HDL cholesterol ratio (MHR) and endothelial function in patients with type 2 diabetes (T2DM). Methods. 243 patients diagnosed with T2DM were enrolled in this cross‐sectional study. Patients were divided into two groups by flow‐mediated dilation (FMD) quintile as nonendothelial dysfunction (FMD ≥ 6.4%) and endothelial dysfunction (FMD < 6.4%). The relationship between MHR and FMD was analyzed using Spearman’s correlation, partial correlation, and multiple logistic regression analysis. ROC curve was fitted to evaluate the ability of MHR to predict endothelial dysfunction. Results. Endothelial dysfunction was present in 193 (79%) patients. Patients with endothelial dysfunction had higher MHR (p < 0.05) than those without endothelial dysfunction. Furthermore, MHR had a significantly positive correlation with endothelial dysfunction (r = 0.17, p < 0.05), and the positive association persisted even after controlling for confounding factors (r = 0.14, p < 0.05). Logistic regression showed that MHR was an independent contributor for endothelial dysfunction (OR: 1.35 (1.08, 1.70), p < 0.05) and the risk of endothelial dysfunction increases by 61% with each standard deviation increase in MHR (OR: 1.61 (1.12, 2.30), p < 0.05) (model 1). After adjusting for sex, age, BMI, disease course, hypertension, smoking, and drinking (model 2) as well as HbA1c, HOMA‐IR, C‐reactive protein, and TG (model 3), similar results were obtained. In ROC analysis, the area of under the ROC curve (AUC) for MHR was 0.60 (95% CI 0.52‐0.69, p < 0.05). Conclusion. MHR was independently associated with endothelial dysfunction in T2DM patients. It could be a new biomarker for vascular endothelial function assessment.

The conclusion between Connecting peptide (C-peptide) and diabetic chronic complication was controversial. The purpose of this study is to explore the possible association between average C-peptide with diabetic retinopathy (DR) progression in Chinese patients with type 2 diabetes. This is a retro-prospective study. 622 patients with type 2 diabetes were included. DR was evaluated using non-mydriatic fundus photography and DR progression was defined as any deterioration of either eye. Fasting and postprandial c-peptide levels were assayed at baseline and follow-up period. Differences between continuous variables were compared using the Mann–Whitney U test; and categorical variables were analyzed by the chi-square test. Correlation between parameters and 30-minute postprandial C-peptide were determined by Spearman correlation test. The relationship between C-peptide and DR progression was evaluated by multivariable binary logistic regression. Two-tailed P-values < 0.05 were regarded as statistically significant. DR was present in 162 (26.0%) patients at baseline, and 26.4% of patients were found progression of DR at follow-up. Patients with progression of DR had lower average levels of 30-minute postprandial C-peptide (2.01 ng/ml vs. 2.6 ng/ml, p = 0.015) and 120-minute postprandial C-peptide (3.17 ng/ml vs. 3.92 ng/ml, p < 0.029), as well as average increment of 30-minute (0.41 ng/ml vs. 0.64 ng/ml, p = 0.015) and 120-minute postprandial C-peptide (1.48 ng/ml vs. 1.93 ng/ml, p < 0.017), than those without DR aggravation. Multivariate logistic regression analysis determined that 30-minute postprandial C-peptide and its increment were related to reduced odds ratios for DR progression (odds ratios [OR] = 0.83 and 0.74, respectively). Our results suggest that the Average 30-minute post-prandial C-peptide and increment were negatively correlated with DR progression, which further demonstrates the importance to preserve β-cell residual function in the prevention for DR progression. Not applicable.

Branched-chain amino acid (BCAA) has been reported to be associated with obesity, the association of BCAA with visceral fat area (VFA) and subcutaneous fat area (SFA) remained unclear in patients with type 2 diabetes. This cross-sectional study was conducted in 284 patients with type 2 diabetes mellitus. Enzyme-linked immunospecific assay was used to measure levels of serum BCAA and branched-chain keto acid (BCKA). VFA and SFA were measured with bio-impedance analysis method. The association between BCAA and VFA was calculated using Pearson correlation and multivariable linear regression analysis. There were significant differences in the means of body mass index, waist circumstance, SFA and VFA among the three groups divided by total BCAA tertiles (all p < 0.05). Compared to patients with lower levels of serum BCAA (the lower tertile group), the means of VFA and SFA were significantly larger in the middle and upper tertile groups (all p < 0.05). However, the differences in above obesity parameters were nonsignificant according to various BCKA tertiles. Pearson correlation analysis also demonstrated that BCAA levels were positive associated with each obesity parameter (p < 0.05). Nevertheless, multivariable linear regression analysis showed that levels of serum BCAA were correlated with VFA, BMI and WC (all p < 0.05) rather than SFA after adjusted for other confounders. levels of serum BCAA were more closely correlated with VFA than SFA, prospective studies should be warranted to further explore the mechanism mediating BCAA and visceral fat accumulation in Human beings. Not applicable.