Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve glycemic control, promote weight loss, reduce insulin requirements, and confer cardiometabolic benefits in type 2 diabetes mellitus (T2DM). This audit evaluated glycemic and metabolic outcomes of GLP-1 RAs in T2DM patients at a single-centre diabetes clinic. Methodology: This audit included T2DM patients who initiated GLP1 RAs between January 2022 and March 2025 at Hospital Sultan Abdul Halim. Primary outcomes were changes in hemoglobin A1c (HbA1c), body weight, and body mass index (BMI) at 3 and 12 months. Secondary outcomes included percentage weight loss, changes in systolic blood pressure (SBP), insulin total daily dose (TDD), low-density lipoprotein (LDL) cholesterol, gastrointestinal adverse effects, and treatment discontinuation. Results: Sixteen patients were included; median age was 58.5 years (interquartile range [IQR] 47.5–65), and 56.3% were female. Median diabetes duration was 15 years (IQR 11.5–20.3). Median HbA1c decreased from 9.7% (IQR 8.6–10.4) at baseline to 8.8% (IQR 7.7–9.1) at 3 months and 7.8% (IQR 7.0–8.5) at 12 months. Body weight decreased from 88.1 kg (IQR 79.5–122.1) at baseline to 85.0 kg (IQR 75.9–113.7) at 3 months and 82.0 kg (IQR 74.8–117.3) at 12 months. BMI decreased from 37.8 kg/m² (IQR 31.7–47.1) to 37.3 kg/m² (IQR 30.7–45.5) at 3 months and 36.0 kg/m² (IQR 30.1–45.6) at 12 months. At 12 months, weight loss was 5.8% (IQR 3.0–8.0), with 56.5% achieving >5% weight reduction. In all, 93.8% achieved >1% HbA1c reduction. Mean SBP decreased by 10 ± 20 mmHg, LDL cholesterol 0.29 mmol/L (IQR -0.77 to 0.07), and insulin TDD 8 units/day (IQR -13 to 10). No gastrointestinal adverse effects reported. Three patients (18.8%) discontinued treatment due to excessive weight loss, treatment plateau, and limited drug availability. Conclusion From our single-centre experience, the observed improvements in glycemic and metabolic outcomes support the benefits of GLP-1 RAs in managing T2DM.
Diabetes Mellitus, Type 2 ; Glucagon-Like Peptide-1 Receptor Agonists ; Clinical Audit

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) induce clinically meaningful weight reduction in patients with type 2 diabetes mellitus (T2DM), but real-world data in Southeast Asian populations are limited. This study evaluated the effectiveness of GLP-1 RAs in achieving clinically significant weight loss in Malaysian patients with obesity and T2DM. Methodology: A retrospective cohort study was conducted among adults with T2DM and obesity attending the Endocrinology Clinic at Hospital Sultan Abdul Aziz Shah between January 2023 and December 2024. Patients receiving GLP-1 RAs (semaglutide or liraglutide) were compared with those on standard care. Anthropometric outcomes were assessed over 6–12 months, with weight loss thresholds of ≥3, ≥5, and ≥10%. Between-group comparisons used Fisher’s exact test, and odds ratios (OR) were calculated. Results: Eighty-five patients were included (GLP-1, n = 47; control, n = 38). The GLP-1 group achieved significantly higher rates of any weight loss (70.0% vs 41.2%; OR = 3.33, p = 0.019) and ≥3% weight loss (42.5% vs 14.7%; OR = 4.29, p = 0.011). Number needed to treat was 3–4 patients. Proportions achieving ≥5 and ≥10% weight loss were higher in the GLP-1 group but did not reach statistical significance. Conclusion GLP-1 RA therapy significantly improves the likelihood of clinically meaningful weight loss in Malaysian patients with obesity and T2DM. These findings support the integration of GLP-1 RAs into routine obesity management strategies in Southeast Asia.
Humans ; Diabetes Mellitus, Type 2 ; Glucagon-Like Peptide-1 Receptor Agonists ; Weight Loss

Introduction: While Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are effective for weight reduction in type 2 diabetes mellitus (T2DM), interindividual variability exists. Lifestyle factors, particularly baseline physical activity, may modify weight loss outcomes. This study examined whether baseline activity influences GLP-1 RA efficacy in Malaysian patients. Methodology: A retrospective cohort of adults with obesity and T2DM receiving GLP-1 RAs (semaglutide or liraglutide) from January 2023 to December 2024 was analyzed. Baseline physical activity was classified as active or inactive. Primary outcomes were achievement of ≥3 and ≥5% weight loss over 6–12 months. Associations were assessed using Fisher’s exact test and logistic regression. Results: Among GLP-1-treated patients, those reporting baseline physical activity were more likely to achieve ≥3% weight loss and demonstrated trends toward higher, ≥5%, weight loss. Logistic regression suggested baseline activity increased the odds of clinically meaningful weight reduction, though statistical significance was limited by sample size. Conclusion Baseline physical activity may enhance GLP-1 receptor agonist-mediated weight loss in obese patients with T2DM. Integrating lifestyle interventions with pharmacotherapy may optimize treatment outcomes. Larger prospective studies are warranted to confirm these findings.
Humans ; Glucagon-Like Peptide-1 Receptor Agonists ; Exercise ; Weight Loss ; Obesity ; Diabetes Mellitus, Type 2

OBJECTIVE: To elucidate the effect of Huanglian-Renshen-Decoction (HRD) on ameliorating type 2 diabetes mellitus by maintaining islet β -cell identity through regulating paracrine and endocrine glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) in both islet and intestine. METHODS: The db/db mice were divided into the model (distilled water), low-dose HRD (LHRD, 3 g/kg), high-dose HRD (HHRD, 6 g/kg), and liraglutide (400 µ g/kg) groups using a random number table, 8 mice in each group. The db/m mice were used as the control group (n=8, distilled water). The entire treatment of mice lasted for 6 weeks. Blood insulin, glucose, and GLP-1 levels were quantified using enzyme-linked immunosorbent assay kits. The proliferation and apoptosis factors of islet cells were determined by immunohistochemistry (IHC) and immunofluorescence (IF) staining. Then, GLP-1, GLP-1R, prohormone convertase 1/3 (PC1/3), PC2, v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MafA), and pancreatic and duodenal homeobox 1 (PDX1) were detected by Western blot, IHC, IF, and real-time quantitative polymerase chain reaction, respectively. RESULTS: HRD reduced the weight and blood glucose of the db/db mice, and improved insulin sensitivity at the same time (P<0.05 or P<0.01). HRD also promoted mice to secrete more insulin and less glucagon (P<0.05 or P<0.01). Moreover, it also increased the number of islet β cell and decreased islet α cell mass (P<0.01). After HRD treatment, the levels of GLP-1, GLP-1R, PC1/3, PC2, MafA, and PDX1 in the pancreas and intestine significantly increased (P<0.05 or P<0.01). CONCLUSION HRD can maintain the normal function and identity of islet β cell, and the underlying mechanism is related to promoting the paracrine and endocrine activation of GLP-1 in pancreas and intestine.
Animals ; Glucagon-Like Peptide 1/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Glucagon-Like Peptide-1 Receptor/metabolism* ; Insulin-Secreting Cells/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Blood Glucose/metabolism* ; Insulin/blood* ; Mice ; Intestinal Mucosa/pathology* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Islets of Langerhans/pathology*

OBJECTIVES: To investigate the effects of live combined Bacillus subtilis and Enterococcus faecium (LCBE) on glucose and lipid metabolism in mice with type 2 diabetes mellitus (T2DM) and circadian rhythm disorder (CRD) and explore the possible mechanisms. METHODS: KM mice were randomized into normal diet (ND) group (n=8), high-fat diet (HFD) group (n=8), and rhythm-intervention with HFD group (n=16). After 8 weeks of feeding, the mice were given an intraperitoneal injection of streptozotocin (100 mg/kg) to induce T2DM. The mice in CRD-T2DM group were further randomized into two equal groups for treatment with LCBE (225 mg/kg) or saline by gavage; the mice in ND and HFD groups also received saline gavage for 8 weeks. Blood glucose level of the mice was measured using a glucometer, and serum levels of Bmal1, PER2, insulin, C-peptide and lipids were determined with ELISA. Colon morphology and hepatic lipid metabolism of the mice were examined using HE staining and Oil Red O staining, respectively, and fecal short-chain fatty acids (SCFAs) was detected using LC-MS; GPR43 and GLP-1 expression levels were analyzed using RT-qPCR and Western blotting. RESULTS: Compared with those in CRD-T2DM group, the LCBE-treated mice exhibited significant body weight loss, lowered levels of PER2, insulin, C-peptide, total cholesterol (TC) and LDL-C, and increased levels of Bmal1 and HDL-C levels. LCBE treatment significantly increased SCFAs, upregulated GPR43 and GLP-1 expressions at both the mRNA and protein levels, and improved hepatic steatosis and colon histology. CONCLUSIONS LCBE ameliorates lipid metabolism disorder in CRD-T2DM mice by reducing body weight and improving lipid profiles and circadian regulators possibly via the SCFAs/GPR43/GLP-1 pathway.
Animals ; Mice ; Lipid Metabolism ; Diabetes Mellitus, Type 2/metabolism* ; Enterococcus faecium ; Glucagon-Like Peptide 1/metabolism* ; Bacillus subtilis ; Diabetes Mellitus, Experimental/metabolism* ; Circadian Rhythm ; Blood Glucose/metabolism* ; Receptors, G-Protein-Coupled/metabolism* ; Fatty Acids, Volatile/metabolism* ; Male ; Chronobiology Disorders/metabolism*

Humans ; Glucagon-Like Peptide-1 Receptor/agonists* ; Diabetic Cardiomyopathies/drug therapy* ; Diabetes Mellitus, Type 2

Obesity is an important risk factor of type 2 diabetes (T2D), which has become an important factor threatening human health. However, no perfect drug choice for obesity exists. Semaglutide is a kind of human glucagon-like peptide-1 (GLP-1) analog that promotes insulin secretion while inhibiting glucagon secretion through a glucose concentration-dependent mechanism. GLP-1 can also delay stomach emptying and suppress appetite to help lose weight. This review summarizes clinical evidence of the semaglutide effect on T2D and obesity and establishes expectations on future clinical trials for obesity treatment.
Diabetes Mellitus, Type 2/drug therapy* ; Glucagon-Like Peptide-1 Receptor/therapeutic use* ; Glucagon-Like Peptides ; Humans ; Hypoglycemic Agents/therapeutic use* ; Motivation ; Obesity/drug therapy*

Peptide dual agonists toward both glucagon-like peptide 1 receptor (GLP-1R) and glucagon receptor (GCGR) are emerging as novel therapeutics for the treatment of type 2 diabetes mellitus (T2DM) patients with obesity. Our previous work identified a Xenopus GLP-1-based dual GLP-1R/GCGR agonist termed xGLP/GCG-13, which showed decent hypoglycemic and body weight lowering activity. However, the clinical utility of xGLP/GCG-13 is limited due to its short in vivo half-life. Inspired by the fact that O-GlcNAcylation of intracellular proteins leads to increased stability of secreted proteins, we rationally designed a panel of O-GlcNAcylated xGLP/GCG-13 analogs as potential long-acting GLP-1R/ GCGR dual agonists. One of the synthesized glycopeptides 1f was found to be equipotent to xGLP/GCG-13 in cell-based receptor activation assays. As expected, O-GlcNAcylation effectively improved the stability of xGLP/GCG-13 in vivo. Importantly, chronic administration of 1f potently induced body weight loss and hypoglycemic effects, improved glucose tolerance, and normalized lipid metabolism and adiposity in both db/db and diet induced obesity (DIO) mice models. These results supported the hypothesis that glycosylation is a useful strategy for improving the in vivo stability of GLP-1-based peptides and promoted the development of dual GLP-1R/GCGR agonists as antidiabetic/antiobesity drugs.
Mice ; Animals ; Glucagon-Like Peptide 1/metabolism* ; Receptors, Glucagon/therapeutic use* ; Xenopus laevis/metabolism* ; Diabetes Mellitus, Type 2/drug therapy* ; Glycopeptides/therapeutic use* ; Obesity/drug therapy* ; Hypoglycemic Agents/pharmacology* ; Peptides/pharmacology*

Type 2 diabetes is a high-profile global public health problem, particularly in Asia. The young age of onset, low body mass index, and early appearance of pancreatic islet dysfunction are characteristics of Asian patients with T2DM. Metabolic surgery has become the standard treatment for T2DM patients and can significantly improve T2DM through a variety of mechanisms including modulation of energy homeostasis and reduction of body fat mass. Indeed, restoration of islet function also plays an integral role in the remission of T2DM. After metabolic surgery, islet function in Asian T2DM patients has improved significantly, with proven short-term and long-term effects. In addition, islet function is an important criterion and reference for patient selection prior to metabolic surgery. The mechanism of islet function improvement after metabolic surgery is not clear, but postoperative anatomical changes in the gastrointestinal tract leading to a number of hormonal changes seem to be the potential cause, including glucagon-like peptide-1, gastric inhibitory polypeptide, peptide YY, ghrelin, and cholecystokinin. The authors analyzed the current retrospective and prospective studies on the effect of metabolic surgery on the islet function of Asian T2DM patients with a low BMI and its mechanism, summarized the clinical evidence that metabolic surgery improved islet function in Asian T2DM patients with a low BMI, and discussed its underlying mechanism. It is of great significance for realizing personalized and precise treatment of metabolic surgery and further improving its clinical benefits.
Bariatric Surgery ; Body Mass Index ; Cholecystokinin/therapeutic use* ; Diabetes Mellitus, Type 2/surgery* ; Gastric Inhibitory Polypeptide/therapeutic use* ; Ghrelin/therapeutic use* ; Glucagon-Like Peptide 1/therapeutic use* ; Humans ; Peptide YY/therapeutic use* ; Prospective Studies ; Retrospective Studies ; Treatment Outcome

Intestinal adaptation is a spontaneous compensation of the remanent bowel after extensive enterectomy, which improves the absorption capacity of the remanent bowel to energy, fluid and other nutrients. Intestinal adaptation mainly occurs within 2 years after enterectomy, including morphological changes, hyperfunction and hyperphagia. Intestinal adaptation is the key factor for patients with short bowel syndrome to weaning off parenteral nutrition dependence and mainly influenced by length of remanent bowel, type of surgery and colon continuity. In addition, multiple factors including enteral feeding, glucagon-like peptide 2 (GLP-2), growth hormone, gut microbiota and its metabolites regulate intestinal adaptation via multi-biological pathways, such as proliferation and differentiation of stem cell, apoptosis, angiogenesis, nutrients transport related protein expression, gut endocrine etc. Phase III clinical trials have verified the safety and efficacy of teduglutide (long-acting GLP-2) and somatropin (recombinant human growth hormone) in improving intestinal adaptation, and both have been approved for clinical use. We aim to review the current knowledge about characteristics, mechanism, evaluation methods, key factors, clinical strategies of intestinal adaptation.
Humans ; Adaptation, Physiological ; Glucagon-Like Peptide 2/therapeutic use* ; Intestines/surgery* ; Parenteral Nutrition ; Short Bowel Syndrome/surgery*