Use Of Glucagon-like Peptide-1 Receptor Agonists Research Articles

Glucose lowering drugs with proven cardiovascular benefit following acute coronary syndrome in type 2 diabetes: treatment gaps and outcomes

Abstract Background and Aims Real-world data on the implementation and prognostic impact of glucose-lowering drugs with proven cardiovascular benefits in patients with type 2 diabetes (T2D) following acute coronary syndromes (ACS) is limited. We investigated the utilization and treatment patterns of sodium-glucose contrasporter-2 inhibitors (SGLT2I) and glucagon-like peptide-1 receptor-agonists (GLP1RA) in T2D patients experiencing ACS, and analyzed their association with mortality and major adverse cardiovascular events (MACE) including recurrent ACS, acute revascularization, heart failure or ischemic stroke. Methods Retrospective analysis of 9,756 patients with T2D from a nationwide healthcare organization hospitalized with ACS between 01/2019 and 01/2022. Drug prescriptions were estimated pre-hospitalization, 90-days and 1-year following hospitalization. The association between SGLT2I and/or GLP1RA treatment with MACE and mortality was investigated using time-dependent Cox regression analysis with multivariable adjustment. Results Prescription rates (prehospitalization, 90-days and 1-year posthospitalization) of GLP1RA were 13%, 13.2%, and 18%, and of SGLT2I were 23.9%, 33.6% and 42.7%, respectively. At 1-year, 13.9% prescribed both therapeutic groups. The use of SGLT2I and/or GLP1RA was higher in younger age-groups, and increased from 2019 to 2021 (38.1% to 59.2%). The adjusted hazard ratio for the association of pre- or post-hospitalization SGLT2I and/or GLP1RA treatment with mortality and MACE was 0.724 (0.654-0.801) and 0.974 (0.909-1.043), respectively. Conclusions In real-world practice of patients with T2D experiencing ACS, implementation of SGLT2I and particularly GLP1RA was suboptimal, both early and 1-year following hospitalization, emphasizing the need to improve medical care. Treatment with SGLT2I and/or GLP1RA was associated with favorable impact on mortality but not MACE.Graphical Abstract

The Therapeutic Potential of GLP-1 Receptor Agonists in the Management of Hidradenitis Suppurativa: A Systematic Review of Anti-Inflammatory and Metabolic Effects

Background: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are synthetic peptides that mimic the natural activity of GLP-1, widely known for lowering blood glucose levels and promoting weight reduction. These characteristics make them a valuable tool in managing type 2 diabetes and obesity-related conditions. Recent findings indicate that GLP1-RAs may also offer therapeutic benefits in managing hidradenitis suppurativa (HS), a chronic inflammatory skin disorder closely associated with metabolic abnormalities, including obesity, diabetes, and dyslipidemia. This review explores the potential role of GLP1-RAs in managing HS. Methods: A systematic review was conducted by searching electronic databases, including MEDLINE and Google Scholar, without date limitations. Key search terms included “GLP-1” or “GLP-1 agonists” combined with “hidradenitis suppurativa” or “acne inversa”. Inclusion criteria were set for studies reporting on the use of GLP1-RAs as a treatment for HS, with articles discussing theoretical applications excluded. Data synthesis included findings from 25 relevant studies. Results: The analysis revealed that GLP1-RAs, specifically liraglutide and semaglutide, led to significant reductions in weight and systemic inflammation in HS patients. Notably, improvements in lesion severity and quality of life were reported. The anti-inflammatory effects of GLP1-RAs were attributed to the suppression of key inflammatory pathways involving TNF-α, IL-17, and NF-κB. Conclusions: GLP1-RAs demonstrate significant potential as an adjunct therapy for HS, addressing both the metabolic and inflammatory aspects of the condition. While early results are promising, further research is necessary to determine their long-term efficacy in managing HS.

Glucagon-like peptide-1 receptor agonists before upper gastrointestinal endoscopy and risk of pulmonary aspiration or discontinuation of procedure: cohort study

ObjectiveTo assess whether use of glucagon-like peptide-1 (GLP-1) receptor agonists before upper gastrointestinal endoscopy is associated with increased risk of pulmonary aspiration or discontinuation of the procedure compared with sodium-glucose...

Characterizing GLP-1 Receptor Agonist Use in Preadolescent and Adolescent Populations

This cross-sectional study examines the characteristics of preadolescent and adolescent populations who received glucagon-like peptide-1 (GLP-1) receptor agonists.

Approach to the patient with thyroid nodules: considering GLP-1 receptor agonists.

Glucagon-like peptide 1 receptor agonists (GLP1RA) have rapidly changed the landscape of diabetes and obesity treatment. Enthusiasm for their use is tempered with concerns regarding their risk for inducing C-cell tumors based on preclinical studies in rodents. A black-box warning from the United States Food and Drug Administration (USFDA) recommends against using GLP1RA in patients with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2A or 2B (MEN2), providing clear guidance regarding this cohort of patients. However, emerging data also suggest an increased incidence of differentiated thyroid cancer (DTC) in patients treated with these agents. Other studies, though, have not confirmed an association between GLP1RA and DTC. With conflicting results concerning thyroid cancer risk, there is no clear consensus regarding the optimal approach to screening patients prior to initiating the medications and/or evaluating for thyroid cancer during GLP1RA treatment. Within the context of patient cases, this review will summarize the existing data, describe ongoing controversies, and outline future areas for research regarding thyroid cancer risk with GLP1RA use.

Glucagon-like peptide-1 receptor agonists significantly affect the quality of bowel preparation for colonoscopy.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) affect gastrointestinal motility, slowing gastric emptying and colonic transit. GLP-1RAs have an impact on gastric residue before endoscopy, but only limited data are available regarding its effect on the adequacy of colonic preparation. We investigated the association between GLP-1RA use and inadequate bowel preparation (IBP) for colonoscopy. We performed a multicenter retrospective study with GLP-1RA cases matched with controls (using propensity scores for age, sex, diabetes mellitus [DM], obesity, and co-morbidities). Data on demographics, medication use, procedural indications, and colonoscopy findings were collected. IBP ("poor preparation" on Aronchik scale or Boston Bowel preparation scale <5) was the primary outcome. 4876 patients treated with GLP-1RAs were included in the analysis and compared with 4876 controls selected from 333 648 patients without GLP-1RA use. Among the GLP-1RA patients, 10% (n = 487) had IBP compared with 197 (4%) of the control group (P<0.001). Subgroup analysis showed a higher rate of IBP among diabetic patients treated with GLP-1RA (284/2364 [12%]) than among diabetic patients without GLP-1RA treatment (118/2364 [5%]; P<0.001). Additionally, 203/2512 nondiabetic patients treated with GLP-1RAs had IBP (8%) compared with 79 of the nondiabetic non-GLP-1RA group (3%; P<0.001). On multivariate analysis, diabetes and GLP-1RA use were both found to be independent risk factors for IBP (odds ratio [OR] 1.4 and OR 2.7, respectively; both P<0.001). Our findings highlight the necessity for special attention and tailored recommendations for both diabetic and nondiabetic patients treated with GLP-1RAs in terms of colonic preparation prior to colonoscopy.

Glucagon-like peptide-1 receptor agonists improve outcomes in individuals with type 2 diabetes with and without heart failure

BackgroundThe effectiveness of glucagon-like peptide-1 receptor agonists (GLP1Ras) for prevention of heart failure (HF) in patients with type 2 diabetes (T2DM) without HF and for risk of death in patients with T2DM with HF has not been fully elucidated in routine clinical practice. MethodsUsing the real-world global electronic medical record TriNetX database, individuals with T2DM and with or without HF who initiated either GLP1Ras or sitagliptin from 2017 to 2020 were retrospectively analyzed. In individuals with T2DM without HF, the primary outcome was a composite of all-cause mortality and a new diagnosis of HF within three years. In individuals with T2DM with HF, the primary outcome was all-cause mortality within three years. Propensity-score (PS) matching was used to adjust for over 100 baseline characteristics. ResultsA total of 65,598 individuals with T2DM without HF starting a GLP1Ras were PS matched with 65,598 starting sitagliptin. GLP1Ras were associated with a lower incidence of the composite endpoint (10.5 % versus 11.8 %, hazard ratio [HR] 0.82, [0.80–0.85], p < 0.001), mortality (HR 0.66 [0.63–0.69]) and new diagnosis of HF (HR 0.92 [0.88–0.96]). There were 6002 individuals in each group matched for T2DM and HF. Mortality was lower in the GLP1Ras group (17.6 % versus 22.8 %, HR 0.70 [0.65–0.76], p < 0.001). Results were consistent across subgroups. ConclusionsIn this global real-world data analysis, GLP1Ra use was associated with a lower risk of death and HF in individuals with T2DM without HF, and lower risk of death in those with HF.

A retrospective evaluation of glucagon-like peptide-1 receptor agonists in systemic lupus erythematosus patients.

Glucagon-like peptide-1 receptor agonists (GLP1-RA) are an emerging class of medications with demonstrated promise in improving cardiometabolic outcomes. Whether these drugs may be useful in mitigating the cardiac risk associated with SLE remains unknown, and a recent case of drug induced lupus secondary to GLP1-RA use calls the safety of GLP1-RAs in SLE patients into question. Accordingly, this retrospective analysis was initiated to evaluate outcomes of GLP1-RAs in SLE. All patients in the NYU Lupus Cohort who had used a GLP1-RA were eligible for inclusion. Patient characteristics were assessed at baseline (most recent rheumatology visit prior to starting GLP1-RA), 1-4 months, and 6-10 months after GLP1-RA initiation. Of the 1211 patients in the cohort, only 24 had received a GLP1-RA. Six were excluded due to insufficient documentation regarding duration of medication use. Of the remaining 18 (median age 50), 17 (94%) were female and 9 (50%) were white. There was one mild-to-moderate flare at 6-10 months, but no patients accumulated new SLE criteria during the follow up period. Compared with baseline, median BMI was reduced by 3% at 1-4 months (p= 0.002) and 13% at 6-10 months (p= 0.001). Nine (50%) patients were initially denied insurance coverage for a GLP1-RA. While limited by a small sample size, this descriptive study showed that GLP1-RAs did not trigger flares above expected background rates and were associated with significantly decreased BMI. Future studies exploring the potential benefits of GLP1-RAs in patients with SLE are warranted.

8139 Examining the Association of GLP1-RA or DPP4i with Bullous Skin Diseases in Veterans

Abstract Disclosure: S. Saad-Omer: None. M. Kinaan: None. N. Sami: None. I. Mansi: None. Introduction: Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are Autoimmune Blistering Disorders (AIBDs). GLP-1 Receptor Agonists (GLP1-RA) and Dipeptidyl peptidase 4 inhibitors (DPP4i) have been noted in various case reports and case control studies to be linked with certain AIBDs; however, their overall role in these diseases is not completely understood, despite the exponential increase in use of these medications. This study aims to be the first study to investigate the association of DPP-4 inhibitors and GLP-1 agonists with incidence of AIBD, PV, and BP in a large cohort of American veterans. Methods: This retrospective cohort study of veterans enrolled in the Veterans Health Administration (VHA) used Corporate Data Warehouse (CDW). We extracted data of patients from fiscal years (FY) 2006 to end of FY 2021 who filled either GLP1-RA or DPP4i prescriptions. CDW is a comprehensive data source that encompasses vital status, demographic data, inpatient and outpatient diagnoses and procedure codes, vital signs, laboratory data, and pharmacy fill data. The study groups included: 1) GLP1-RA group: patients who initiated GLP1-RA; and 2) DPP4i group: patients who initiated DPP4i. Our primary outcome was the incidence of AIBDs. We compared baseline characteristics of patients who experienced the outcome and those who did not among GLP1-RA or DDP4i users. We, thereafter, examined factors associated with incidence of AIBD, PV, and BP among GLP1-RA users and DPP4i users. Results: The initial cohort of GLP1-RA or DPP4i users comprised a total of 415,895 patients, from which we excluded 397 (0.095%) patients with prior bullous skin diseases before starting GLP1-RA or DPP4i medications. Overall, a total of 154 patients developed PV/BP disease after initiation of either DPP4i or GLP1-RA. Of these 154 patients, 123 of these patients were on DPP4i and 31 of these patients were on GLP1-RA. The mean age (SD) of PV/BP patients was 72 (11) years compared to an average age of 66 (10) years in patients who did not develop PV/BP. Patients were also found to be predominately white (77.9%). Factors associated with increased risk of BP were use of DPP4i (Odds Ratio [OR] 1.90, 95% confidence interval [95% CI: 1.14-3.47, p=&amp;lt;0.01), and older age (OR: 1.07, 95%CI: 1.04-1.09, p&amp;lt;0.01). Use of GLP1-RA or DPP4i was not associated with PV incidence. (OR: 1.31, 95% CI: 0.65-2.62, p=&amp;lt;0.45). Conclusion: In conclusion, our study supports existing literature that DPP4i use is associated with an increased risk of developing BP. Our data does not find association with GLP-1 agonists nor DPP4 inhibitors in increasing the risk of PV. Presentation: 6/3/2024

8687 The Efficacy of GLP1 Receptor Agonists in Obese Women with PCOS in Promoting Weight Loss and Hormonal Regulation: A Systematic Review and Meta-Analysis

Abstract Disclosure: B. Austregesilo Athayde H Morais: None. V.M. Prizão: None. B. Ximenes Mendes: None. M.L. Defante: None. O.C. Martins: None. T.L. Correa: None. M.D. De Moura de Souza: None. Background: GLP1 receptor antagonists (GLP1a) are known for their efficacy in promoting weight loss among obese and diabetic patients. However, their impact on weight reduction and hormonal regulation in obese females with polycystic ovarian syndrome (PCOS) remains understudied. Therefore, we aimed to perform a meta-analysis exploring the efficacy of GLP1a against placebo for ameliorating symptoms of PCOS. Hypothesis: The use of GLP1 receptor agonists in obese women with PCOS reduces body mass index and waist circumference as well as normalizes hormone levels such as total testosterone, total cholesterol, and HOMA-IR. Methods: We conducted a comprehensive search of PubMed, Cochrane, and Scopus databases to identify trials comparing GLP1a against placebo among women diagnosed with PCOS based on the Rotterdam Criteria. Our primary outcomes of interest included body mass index (BMI), triglycerides, waist circumference, total testosterone, total cholesterol, and HOMA-IR. We performed data extraction and quality assessment for studies that met the inclusion criteria. Subsequently, we conducted a statistical analysis using Review Manager 5.1.7 (Cochrane Collaboration). We evaluated heterogeneity using I² statistics. Results: We included 176 participants from 4 studies, which all were RCTs. GLP1a was used to treat 111 (63.06%) patients. Analyzed outcomes included waist circumference (MD: −5.16 cm; 95% CI: −6.11 to −4.21; p &amp;lt; 0.00001), total testosterone (MD: −1.33; 95% CI: −2.55 to −0.12; p =0.03), BMI (MD: -2.42; 95% CI: -3.10 to -1.74; p &amp;lt; 0.00001), total cholesterol (MD: −0.04; 95% CI: −0.10 to 0.01; p =0.15), HOMA-IR (MD: −0.30; 95% CI: −0.92 to 0.32; p =0.35), Triglycerides (MD: −0.20; 95% CI: −0.30 to −0.11; p &amp;lt; 0.00001) were lower in patients treated with GLP1a compared with placebo. Most patients who discontinued the trials did so because of a nausea side effect. Conclusion: The utilization of GLP1a demonstrates efficacy in reducing body mass index (BMI), triglycerides, waist circumference, total testosterone, total cholesterol, and HOMA-IR. These results signify its viability as a favorable treatment option for managing PCOS in obese females. Presentation: 6/3/2024

8462 Synergistic Outcomes Of hCG And GLP1-RA Combination Therapy: Improved Body Composition And Carbohydrate Metabolism

Abstract Disclosure: F. Comite: None. K. O'Malley: None. Objective: Precision medicine prevents and reverses diseases of aging by way of systematic analysis of body composition and extensive blood biomarkers. Andropause, the age-related reduction of free testosterone (FT) in males, elicits symptoms primarily of muscle loss, decreased libido, and diminished energy. Exogenous testosterone therapy (TTx) subsequently increases lean body mass (LBM) and improves both libido and energy levels in affected males. More recently, stimulation of endogenous testosterone from the testes, human Chorionic Gonadotropin (hCG) has emerged as a compelling physiologic alternative to TTx. Common comorbidities to andropause are DMII and/or obesity. Recent literature surrounds the use of GLP-1 receptor agonists to improve insulin sensitivity in these disorders of carbohydrate metabolism. A primary benefit secondary to GLP-1 use is reduction of fat mass; however, concerns of this monotherapy surround loss of muscle.[1] Remarkably, when treated adjunctly with GLP-1s, hCG therapy significantly mitigates muscle loss while maintaining optimal carbohydrate biomarkers. The efficacy and benefits of hormonal optimization through hCG therapy simultaneous to GLP-1 intervention were investigated. Methods: In this retrospective analysis, a cohort of 20 males ≥30 years of age were reviewed at baseline timepoints and 18 months post treatment-initiation. Participants underwent biweekly hCG and weekly GLP-1 subcutaneous injections. Exclusion criteria restricted use of alternative GLP-1/GIP combination medication. Paired T-Tests were used to determine a relationship between LBM, FT, percent body fat (PBF), fasting glucose (FG), fasting insulin (FI), and HbA1c at each timepoint. Results: Body composition analysis as shown via bioelectrical impedance proved baseline PBF (mean=24.60) significantly reduced post-treatment (p&amp;lt;0.05, mean=18.08) for all participants. In addition, relevant carbohydrate metabolic biomarkers FG, FI, and HbA1c provided significant reductions (p&amp;lt;0.05). Initial FT (mean=67.76) and LBM (mean=150.36) increased significantly at follow-up (p&amp;lt;0.05) with values of 167.55 and 154.91, respectively. Discussion: Using metrics of precision medicine, our interpretation reveals a promising combination therapy for males experiencing andropause. The novel use of hCG to optimize FT levels enhances muscle, while simultaneously, fat loss and reversal of harmful carbohydrate metabolic markers resultant from GLP-1 therapy are achieved. Muscle loss due to overall weight loss is thus ameliorated. Our findings merit further investigation of the magnitude of downstream improvements, particularly in energy and libido.

Use of glucagon-like-peptide 1 receptor agonist in the treatment of childhood obesity.

Pediatric obesity is a growing epidemic. Lifestyle modifications remain central to obesity treatment, however pharmacologic options have gained traction, particularly glucagon-like peptide-1 receptor agonists (GLP-1RA). This review aims to summarize evidence on the use of GLP-1RAs in the management of pediatric obesity, physiological mechanisms of action of GLP-1RAs and their role in appetite regulation and glucose homeostasis and address the challenges and special considerations surrounding GLP-1RA use. Recent studies have highlighted the efficacy of GLP-1RAs, such as exenatide, liraglutide, and semaglutide, in promoting weight loss and improving metabolic parameters in children and adolescents. GLP-1RA's efficacy extends beyond glycemic control to include weight loss mechanisms such as delayed gastric emptying (gastroparesis), and appetite suppression. Semaglutide, the newest GLP-1RA, holds potential for substantial weight loss in adolescents and demonstrates a similar safety and efficacy as seen in adults. GLP-1RAs may offer a promising adjunct therapy for pediatric obesity, particularly in cases where lifestyle interventions alone are insufficient. However, further research is needed to elucidate long-term safety and efficacy outcomes and to address potential disparities in access to care. Overall, this review highlights the relevance and timeliness of incorporating GLP-1RAs into the comprehensive management of pediatric obesity.

Changes in Transient Elastography with Glucagon-Like Peptide-1 Receptor Agonist Use in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Real-World Retrospective Analysis.

Introduction: Current guidelines recommend the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD), especially in patients with comorbid diabetes and obesity. This study investigated the effects of GLP-1RAs on hepatic steatosis and fibrosis in patients with MASLD, as measured by changes in vibration-controlled transient elastography (VCTE) and other clinical parameters in a real-world clinical setting. Methods: We conducted a single-center, retrospective analysis of 96 patients with MASLD from a multidisciplinary care clinic who completed VCTE at baseline and follow-up within 6-24 months to compare changes in controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), as well as other metabolic markers, between GLP-1RA users and nonusers using two-sample t-tests and Wilcoxon rank-sum tests. We also assessed whether improvements in hepatic steatosis, defined as a change in CAP >38 dB/m as previously described in the literature, were associated with improvement in fibrosis. Results: GLP-1RA use resulted in significant improvements in weight (-8.1 kg vs. -3.5 kg, P = 0.009), body mass index (BMI) (-2.9 kg/m2 vs. -1.3 kg/m2, P = 0.012), alanine aminotransferase (-15.0 IU/L vs. -4.0 IU/L, P = 0.017), aspartate aminotransferase (-5.0 IU/L vs. -1.0 IU/L, P = 0.021), glycated hemoglobin (HbA1c) (-0.7% vs. 0.1%, P = 0.019), and CAP (-59.9 dB/m vs. -29.1 dB/m, P = 0.016). Responders also had significant improvements in weight (-9.2 kg vs. -1.9 kg, P < 0.001), BMI (-3.3 kg/m2 vs. -0.7 kg/m2, P < 0.001), diastolic blood pressure (-6.1 mmHg vs. -0.7 mmHg, P = 0.028), HbA1c (-0.8% vs. 0.3%, P < 0.001), and LSM (-1.5 kPa vs. 0.1 kPa, P < 0.001). Conclusions: Patients with MASLD treated with GLP-1RAs showed significant improvements in hepatic steatosis and multiple other metabolic parameters, with weight loss as the proposed mechanism for this liver improvement. In addition, change in CAP >38 dB/m was associated with improvements in LSM and other metabolic parameters, suggesting the clinical utility of VCTE in the surveillance of MASLD.

S541 Glucagon-Like Peptide-1 Receptor Agonist Use and its Potential Impact in Colonoscopy Among Patients Undergoing Colorectal Cancer Screening: A Multicenter Propensity Score Matching Analysis

S541 Glucagon-Like Peptide-1 Receptor Agonist Use and its Potential Impact in Colonoscopy Among Patients Undergoing Colorectal Cancer Screening: A Multicenter Propensity Score Matching Analysis

Effects of glucagon-like peptide-1 receptor agonists on glycated haemoglobin and continuous glucose monitoring metrics as adjunctive therapy to insulin in adults with type 1 diabetes: A meta-analysis of randomized controlled trials.

To conduct a meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on glycated haemoglobin (HbA1c) and continuous glucose monitoring (CGM) metrics as an adjunct to insulin therapy in adults with type 1 diabetes mellitus (T1D). A systematic literature search was conducted through Medline (via PubMed), Cochrane Library, and Google Scholar up to 27 May 2024. Dual-independent study selection, data extraction, and quality assessment were performed. Results were summarized using random-effects meta-analysis. Six RCTs were identified, involving a total of 378 individuals with T1D. The use of GLP-1RAs in addition to standard insulin therapy was associated with a significant reduction in HbA1c (mean difference [MD] -0.21%, 95% confidence interval [CI] -0.36 to -0.06; p = 0.007) and a similar time in range (TIR) compared to placebo (MD -0.22%, 95% CI -2.39 to 1.95; p = 0.84). GLP-1RA therapy resulted in a significantly higher time below range (MD 1.13%, 95% CI 0.50 to 1.76; p < 0.001) and a lower time above range compared with placebo (MD -1.83%, 95% CI -2.51 to -1.15; p < 0.001). Nonsignificant differences were noted for the secondary outcomes, including the mean amplitude of glucose excursion, continuous overall net glycaemic action for 60 min, mean daily glucose, coefficient of variation, and mean standard deviation of weekly glucose levels. Our findings suggest that, in individuals with T1D, add-on therapy with GLP-1RAs does not confer significant benefits in terms of CGM metrics and is associated with a longer time below the target glycaemic range.

GLP-1 receptor agonist-induced diabetic ketoacidosis: A case report.

Glucagon-like peptide-1 is an endogenous incretin that plays an active role in weight loss and hypoglycemia. Dulaglutide is a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), which has been approved for the treatment of patients with type 2 diabetes (T2D). GLP-1RAs can increase insulin secretion and inhibit glucagon release, thereby leading to a decrease in blood glucose levels within the body. Specifically, GLP-1RAs control postprandial blood glucose levels by inhibiting hepatic glucose production and delaying gastric emptying. However, attention should be given to gastrointestinal adverse reactions. There are currently a few cases of GLP-1RA causing diabetic ketoacidosis (DKA). The following report details the case of a 50-year-old Chinese female who has been living with diabetes for 12 years. Initially diagnosed with T2D, she was subsequently identified as a patient with latent autoimmune diabetes in adults (LADA) following treatment. The patient presented severe nausea, vomiting, and fatigue 1 day after injecting dulaglutide 1 time and discontinuing insulin therapy. She was diagnosed with severe DKA in the emergency department. LADA and DKA. Changed from dulaglutide to insulin therapy. After discontinuing dulaglutide and switching to insulin for blood glucose reduction, the patient's DKA was corrected, and blood glucose levels returned to normal. This case suggests that clinicians should be alert to patients with severe DKA in cases of severe gastrointestinal adverse reactions after the use of GLP-1RAs. In addition, in most countries, GLP-1RAs are administered to patients with T2D, but we should consider the use of GLP-1RAs in patients with type 1 diabetes and LADA.

Impact of glucagon-like peptide-1 receptor agonists on diabetic retinopathy: A meta-analysis of clinical studies emphasising retinal changes as a primary outcome.

To determine if glucagon-like peptide-1 receptor agonists (GLP-1RA) are associated with the development and progression of diabetic retinopathy (DR). A systematic search was conducted on PubMed, Cochrane Library, and Embase from inception to February 2024 to identify clinical studies reporting the development of and changes in DR as the primary outcome in patients with type 2 diabetes taking GLP-1RA, insulin, or oral antidiabetic medication (OAD). Two researchers independently completed the search and referred to a third as necessary. Data for meta-analysis was pooled using a random-effects model. Analysis of seven studies representing 242 537 patients showed a significantly decreased risk of incidence of DR between GLP-1RA and insulin use (RR = 0.66, 95% CI (0.48, 0.91), p = 0.01). There was no difference in the risk of DR complications (e.g., vitreous haemorrhage, retinal detachment, or requiring treatment with intravitreal injections, lasers, vitrectomy). Between GLP-1RA and OAD use, there was no difference in the risk of incidence of DR, while there was a significantly increased risk of DR complications (RR = 1.39, 95% CI (1.07, 1.80), p = 0.01). Our findings indicate no elevated risk of incidence of DR linked to GLP-1RA compared to insulin. In fact, GLP-1RA may offer potential advantages over insulin regarding the overall incidence of DR. The increased risk of DR requiring treatment and associated complications in the GLP-1RA group compared to OAD may be due to the transient progression of DR associated with a rapid decrease in HbA1c - a phenomenon not specific to GLP-1RA and warrants further investigation.

Decreased risk of recurrent acute pancreatitis with semaglutide and tirzepatide in people with type 2 diabetes or obesity with a history of acute pancreatitis: A propensity matched global federated TriNetX database-based retrospective cohort study

BackgroundAcute pancreatitis (AP) is a significant health concern with potential for recurrent episodes and serious complications. The risk of recurrence in type 2 diabetes (T2D) or obesity can be influenced by various factors and treatments, including GLP-1 receptor agonists (GLP-1RAs). This study evaluates the risk of recurrent AP among patients with a history of the condition, focusing on the effects of different GLP-1RA treatments. ObjectivesOur objective is to compare the recurrence risks of AP between patients treated with different GLP-1RAs. MethodsWe conducted a retrospective cohort study using the TriNetX platform, encompassing 258,238 individuals with T2D or obesity who have a history of AP. We assessed the recurrence of AP over a five-year period, analyzing data on treatment regimens, with a focus on the use of Semaglutide, Tirzepatide, and other GLP-1RAs. ResultsGLP-1RA users experienced significantly lower recurrence rates of AP, with those without risk factors showing GLP-1RA users had a recurrence rate of 13.8 % compared to 40.9 % for non-users. Semaglutide and Tirzepatide showed the most favorable outcomes; Semaglutide users had lower recurrence rates than Exenatide (10.1 % vs. 27 %) and slightly lower than Dulaglutide (13.6 % vs. 15.4 %), though not statistically significant with Dulaglutide. Tirzepatide users displayed the lowest recurrence risk at 6.2 %, significantly lower than those on Semaglutide (11.7 %). ConclusionsGLP-1RAs, particularly Semaglutide and Tirzepatide, are associated with a reduced risk of recurrent AP in people with T2D or obesity. The differential risk profile between these drugs highlights the need for further studies and personalized treatment plans.

Treatment trajectories for Danish individuals with type 2 diabetes in the era of emerging glucose-lowering therapies.

To analyse patterns of glucose-lowering therapies among people with type 2 diabetes (T2D) in Denmark from 2016 to 2023. We examined time trends in the clinical profiles of people with T2D who initiated different glucose-lowering therapy classes for the first time. We furthermore investigated individual-level treatment trajectories following first-ever glucose-lowering therapy in people with or without cardiorenal disease. The study utilized data from the nationwide Danish health registries and included all individuals who filled a first-ever prescription for metformin, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose co-transporter-2 inhibitors (SGLT-2is) or insulin, excluding those without HbA1c-confirmed T2D or probable type 1 diabetes. We included 260 393 individuals initiating a new glucose-lowering therapy class from 2016 to 2023, during which there were 6- and 3-fold increases in initiators of GLP-1RAs and SGLT-2is, respectively. The median HbA1c level at treatment initiation with GLP-1RAs or SGLT-2is decreased, from 67-68 mmol/mol in 2016-2017 to 57-58 mmol/mol in 2022-2023. Among individuals who initiated metformin as first-line therapy, the proportion who started additional glucose-lowering therapy within 2 years increased from 25% in 2016 to 40% in 2021. Among the 38% of individuals who had established cardiorenal disease when they initiated first-ever glucose-lowering therapy in 2020, 22% used SGLT-2is and 18% GLP-1RAs after 2.5 years, compared with 17% and 21% among initiators without cardiorenal disease, respectively. Our study documents a trend towards earlier T2D treatment intensification and an increase in the use of GLP-1RAs and SGLT-2is in Denmark. However, optimal T2D treatment is still not received by most individuals with early T2D and established cardiorenal disease.

Associations between income/employment status and diabetes care processes, health behaviors, and health outcomes in Japan: A cross-sectional study using claims data linked to a questionnaire survey.

We aimed to explore the associations between income/employment status and diabetes care processes, health behaviors and health outcomes. This cross-sectional study used health insurance claims data between April 2021 and March 2022, and a questionnaire survey between December 2022 and January 2023 in Tsukuba City. The study analyzed the participants with diabetes (other than type 1) from those selected by stratified random sampling. We evaluated diabetes care processes, health behaviors and health outcomes by calculating weighted proportions among the groups. We also assessed the associations between income/employment status and these variables using multivariable modified Poisson regression models. Of the 264 identified participants, 161 (64.2%) were men and 168 (72.8%) were aged ≥65 years old. Compared with the low-income groups, the high-income group had a higher proportion of sodium-glucose cotransporter 2 inhibitors or glucagon-like peptide-1 receptor agonists use (adjusted risk ratio [aRR] 1.70, 95% confidence interval (CI) 1.07-2.72), a higher proportion of attendance to annual health checkups for ≥2 years (aRR 1.68, 95% CI 1.07-2.64) and a lower proportion of all-cause hospitalization (aRR 0.15, 95% CI 0.04-0.48); additionally, the middle-income group had a lower proportion of high total outpatient medical expenses (aRR 0.57, 95% CI 0.35-0.92). Compared to the no work time group, the full-time work group had a lower proportion of exercise habits (aRR 0.59, 95% CI 0.35-0.99) and a higher proportion of good self-reported health (aRR 2.08, 95% CI 1.22-3.55). Several variables were associated with income/employment status. Policy intervention should focus on high-risk groups identified by considering these associations.