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Glucagon-like peptide-1 receptor (GLP-1R) agonists have garnered significant attention for their therapeutic potential in addressing the interconnected health challenges of diabetes, obesity, and cancer. The role of GLP-1R in type 2 diabetes mellitus (T2DM) is highlighted, emphasizing its pivotal contribution to glucose homeostasis, promoting β-cell proliferation, and facilitating insulin release. GLP-1R agonists have effectively managed obesity by reducing hunger, moderating food intake, and regulating body weight. Beyond diabetes and obesity, GLP-1R agonists exhibit a multifaceted impact on cancer progression across various malignancies. The mechanisms underlying these effects involve the modulation of signaling pathways associated with cell growth, survival, and metabolism. However, the current literature reveals a lack of in vivo studies on specific GLP-1R agonists such as semaglutide, necessitating further research to elucidate its precise mechanisms and effects, particularly in cancer. While other GLP-1R agonists have shown promising outcomes in mitigating cancer progression, the association between some GLP-1R agonists and an increased risk of cancer remains a topic requiring more profound investigation. This calls for more extensive research to unravel the intricate relationships between the GLP-1R agonist and different cancers, providing valuable insights for clinicians and researchers alike. [ABSTRACT FROM AUTHOR]

Abstract Objective Newer antidiabetic medications such as sodium‐glucose co‐transporter 2 inhibitors (SGLT2i) and glucagon‐like peptide 1 receptor agonists (GLP1RA) result in weight loss in clinical trials. However, the real‐world effectiveness remains unclear. The magnitude of weight change associated with antidiabetic medication using real‐world data was examined. Methods Patients with diabetes who initiated SGLT2i (n = 906), GLP1RA (n = 782), dipeptidyl peptidase‐4 inhibitors (DPP4i, n = 1881), or sulfonylureas (n = 3255) in Geisinger Health System were identified. Outcomes were percent weight change per year and time to 5% weight loss. Propensity scores were used to account for differences across groups. Results The mean ± SD age of patients was 57.5 ± 14.1 years, 3381 (49.5%) were female, and 6450 (94.5%) had body mass index ≥25 kg/m2. Compared with sulfonylureas, newer antidiabetic medications were associated with significant weight loss (−3.2% [95% confidence interval: −3.8%, −2.6%] per year for SGLT2i; −2.9% [−3.6%, −2.3%] per year for GLP1RA; and −1.7% [−2.1%, −1.3%] per year for DPP4i). SGLT2i and GLP1RA were also associated with significant weight loss compared with DPP4i. Among patients with overweight or obesity, SGLT2i and GLP1RA users were more likely to achieve 5% weight loss compared with sulfonylureas and DPP4i. Conclusions In real‐world practice, SGLT2i and GLP1RA were associated with significant weight loss compared with sulfonylureas and DPP4i. These results may further motivate uptake of SGLT2i and GLP1RA, especially among patients who were overweight or had obesity.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder, primarily characterized by a decrease in insulin secretion and typically accompanied by insulin resistance. When untreated, T2DM is leading to an inevitable long-term complication. However, the novel treatment of T2DM like for example Glucagon-like Peptide-1 receptor agonists (GLP-1 RAs) give new perspectives for the patients to achieve a better glycemic control and additional metabolic improvements. Pharmacogenetics is a field in pharmacotherapy, which investigates the individual response to the medical treatment, according to polymorphic variations in the receptors of the drugs. This review aims to summarize current scientific evidence on the pharmacogenetics of the GLP-1 RA /liraglutide/ and the possible implementation in the treatment of T2D. [ABSTRACT FROM AUTHOR]

Objective: Newer antidiabetic medications such as sodium‐glucose co‐transporter 2 inhibitors (SGLT2i) and glucagon‐like peptide 1 receptor agonists (GLP1RA) result in weight loss in clinical trials. However, the real‐world effectiveness remains unclear. The magnitude of weight change associated with antidiabetic medication using real‐world data was examined. Methods: Patients with diabetes who initiated SGLT2i (n = 906), GLP1RA (n = 782), dipeptidyl peptidase‐4 inhibitors (DPP4i, n = 1881), or sulfonylureas (n = 3255) in Geisinger Health System were identified. Outcomes were percent weight change per year and time to 5% weight loss. Propensity scores were used to account for differences across groups. Results: The mean ± SD age of patients was 57.5 ± 14.1 years, 3381 (49.5%) were female, and 6450 (94.5%) had body mass index ≥25 kg/m2. Compared with sulfonylureas, newer antidiabetic medications were associated with significant weight loss (−3.2% [95% confidence interval: −3.8%, −2.6%] per year for SGLT2i; −2.9% [−3.6%, −2.3%] per year for GLP1RA; and −1.7% [−2.1%, −1.3%] per year for DPP4i). SGLT2i and GLP1RA were also associated with significant weight loss compared with DPP4i. Among patients with overweight or obesity, SGLT2i and GLP1RA users were more likely to achieve 5% weight loss compared with sulfonylureas and DPP4i. Conclusions: In real‐world practice, SGLT2i and GLP1RA were associated with significant weight loss compared with sulfonylureas and DPP4i. These results may further motivate uptake of SGLT2i and GLP1RA, especially among patients who were overweight or had obesity. [ABSTRACT FROM AUTHOR]

The benefits of new glucose-lowering agents on cardiovascular disease have been demonstrated in randomized clinical trials. However, more evidence is required to assess the additive value of a combined therapy based on sodium-glucose transporter inhibitors (SGLT2i) and glucagon-like peptide receptor agonists (GLP1ra) in a real-world population. A nonconcurrent prospective study was conducted using integrated electronic medical records from primary care and hospitals obtained through "big data" technologies in a healthy area in Galicia. The study involved patients who were given SGLT2i, GLP1ra, or both treatments between January 2018 and June 2022 and were categorized as either mono- or combined therapy (SGLT2i, GLP1ra, or both). The cumulative risk for different events: hospitalization or mortality, or both, for 1) coronary artery disease, 2) heart failure, 3) cerebrovascular accident, and all-cause mortality were represented by Kaplan-Meier curves and multivariate Cox regression analysis to obtain the hazard ratio (HR) and (95% confidence interval [CI]). Validation was performed in a subpopulation with propensity score matching. The patients (15,549) who were included were median (standard deviation) 68 (12) years old, with 41% of them being female and 46% experiencing obesity. The median (interquartile range) of follow-up was 19 (8-33) months. The Kaplan-Meier analysis determined that the cumulative risk for coronary artery disease and cerebrovascular accident events was similar among the 3 different therapy groups. However, the combined therapy vs SGLT2i reduced the risk of heart failure events (HR 0.69; 95% CI, 0.56-0.87) or all-cause mortality (HR 0.68; 95% CI, 0.54-0.86). Multivariate Cox regression analysis, after matching with a propensity score, confirmed the benefits of combined therapy regarding SGLT2i or GLP1ra monotherapy. Compared with SGLT2i or GLP1ra alone, combined therapy SGLT2i + GLP1ra reduces heart failure risk and all-cause mortality in a real-world population. [ABSTRACT FROM AUTHOR]

Diabetes is an increasingly common co-morbidity in people living with HIV (PLWH). Given new evidence demonstrating cardiovascular benefits of sodium glucose transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1RA) in diabetic patients, we reviewed medical charts of 262 PLWH at Monash Health through a 1-year retrospective cohort study to determine the rates of their use. Prevalence of diabetes was 13.4% (35) and 60% (21) had microvascular and macrovascular complications. Only 4% (95% CI 0.1%–19.6%) of diabetic patients were receiving SGLT2i and 19% (95% CI 6%–39.4%) were receiving GLP1RA. Prescribers should carefully consider their choice of glucose-lowering medication when treating PLWH. Diabetes is increasingly common among people living with HIV (PLWH). Given new evidence demonstrating cardiovascular benefits of sodium glucose transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1 RA) in diabetic patients, we reviewed medical charts of PLWH at Monash Health to determine the rates of their use and found that only 4% of diabetic patients were receiving SGLT2i and 19% were receiving GLP1 RA. Prescribers should carefully consider their choice of glucose-lowering medication when treating PLWH. [ABSTRACT FROM AUTHOR]