Use Of GLP-1 RAs Research Articles

Pancreatitis Risk Associated with GLP-1 Receptor Agonists, Considered as a Single Class, in a Comorbidity-Free Subgroup of Type 2 Diabetes Patients in the United States: A Propensity Score-Matched Analysis

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly prescribed for the management of type 2 diabetes mellitus (T2DM). However, the potential connection between GLP-1 RAs and the risk of pancreatitis presents a complex and nuanced issue. Although these drugs are effective in improving blood sugar control and cardiovascular health, their association with pancreatitis remains an area of concern. Our study aims to evaluate the association between the use of GLP-1 RAs, considered as a single class, and the risk of pancreatitis in a comorbidity-free subgroup of patients with type 2 diabetes mellitus (T2DM) in the United States. Methods: Data were retrieved from the TriNetX research database using the US Collaborative Network, which included information from 61 healthcare organizations within the U.S. Patients diagnosed with T2DM were categorized into two cohorts: one consisting of the patients prescribed with GLP-1 RAs and the other comprising patients who did not receive GLP-1 RAs. Of this class of medications, the agents analyzed were dulaglutide, lixisenatide, exenatide, liraglutide, and semaglutide. Using a 1:1 propensity score matching (PSM) model, we matched patients of both cohorts based on baseline demographics, comorbidities (hypertensive disorders, ischemic heart disease, gallstones, annular pancreas, alcohol use disorders, hypertriglyceridemia, hypercalcemia, cystic fibrosis, and cannabis use), medications known to cause drug-related pancreatitis, and laboratory values. Results: Of 969,240 patients with T2DM, 9.7% (93,608) were on GLP-1 RA, and 90.3% (875,632) were not. After PSM, the sample included 81,872 patients in each cohort. The risk of pancreatitis between the two groups was not statistically different between the two cohorts at 6 months at (0.1% vs. 0.1%, p = 0.04), and remained without significant increase with time; at 1 year (0.1% vs. 0.2%, p = 0.02), 3 years (0.2% vs. 0.3%, p = 0.001), and 5 years (0.3% vs. 0.4%, p < 0.001). The lifetime risk of developing pancreatitis in patients on GLP-1 RA was lower (0.3% vs. 0.4%, p < 0.001). Conclusions: In our comorbidity-free U.S.-based population with T2DM, the use of GLP-1 RAs did not increase their risk of pancreatitis. Their use was associated with a lower lifetime risk of pancreatitis.

Efficacy of GLP-1 Receptor Agonists on Weight Loss, BMI, and Waist Circumference for Patients With Obesity or Overweight: A Systematic Review, Meta-analysis, and Meta-regression of 47 Randomized Controlled Trials.

To provide an updated synthesis on effects of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on weight, BMI, and waist circumference incorporating newer randomized controlled trials (RCTs), particularly in individuals with overweight or obesity. We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) for RCTs published from inception to 4 October 2024. The search was limited to RCTs evaluating the use of GLP-1 RAs for mean differences from baseline in weight, BMI, and waist circumference in adults with obesity or overweight with or without diabetes. Two independent reviewers performed the literature search and data extraction, resolving disagreements via consensus or third-reviewer consultation. Forty-seven RCTs were included, with a combined cohort of 23,244 patients. GLP-1 RAs demonstrated a mean weight reduction of -4.57 kg (95% CI -5.35 to -3.78), mean BMI reduction of -2.07 kg/m2 (95% CI -2.53 to -1.62), and mean waist circumference reduction of -4.55 cm (95% CI -5.72 to -3.38) compared with placebo. This effect was consistent across diabetes status, GLP-1 RA used, and route of administration. The greatest treatment benefit appeared to favor patients who were younger, female, without diabetes, with higher baseline weight and BMI but lower baseline HbA1c, and treated over a longer duration. Limitations include substantial statistical heterogeneity, in part due to broad inclusion criteria. However, this heterogeneity may improve generalizability by reflecting a wide range of study designs and patient populations. GLP-1 RAs demonstrated significant weight, BMI, and waist circumference reduction benefits in this meta-analysis.

GLP-1 Receptor Agonist Induced Eustachian Tube Dysfunction: Database and Systematic Review of Otolaryngologic Adverse Events.

GLP-1 receptor agonists (GLP-1 RAs) have gained traction in the management of obesity. There is limited literature on the implications of GLP-1 RAs in the field of otolaryngology. We explore the association between GLP-1 RAs with eustachian tube dysfunction (ETD) and patulous ETD (PETD) by review of cases, literature, and the FDA adverse event database (FAERS). We also performed a systematic review using the PRISMA guidelines. We present autophony and aural fullness following GLP-1 agonist use. In both cases, nasal endoscopy confirmed significant loss of tissue bulk of the anterior and posterior ET cushions. The total number of adverse events (AEs) with GLP-1 RAs was 97,237. The proportion of otologic AEs was 958 (0.99%): 515 hypoacusis, 203 vertigo, 97 deafness, 93 tinnitus, 22 ear pain, 21 motion sickness, 5 hyperacusis, 2 ear fullness, and 0 autophony. The largest number of potential ETD-related AEs occurred with dulaglutide (417). The greatest proportion of potential ETD-related AEs occurred with exenatide (1.52%) followed by semaglutide (1.17%) and liraglutide (1.16%). The systematic review using PRISMA guidelines yielded 1,490 initial articles, of which 937 were screened and 10 met the inclusion criteria. The top 3 identified otologic side effects included nasopharyngitis, sinusitis, unspecified dizziness. Ear complaints due to GLP-1 RAs have been reported previously. However, this is the first report of PETD associated with GLP-1 RAs. While literature on GLP-1 RAs and PETD is currently limited, the mechanism is well established as reports of PETD after rapid weight loss, especially in bariatric surgery, are well known. Given the rising use of GLP-1 RAs for weight loss, clinicians should be vigilant in screening for otolaryngologic side effects, especially PET, in this population. Otolaryngologists should be aware and monitor for possible otolaryngologic side effects, particularly PETD, with GLP-1 RA use.

A Comprehensive Review of the Role of GLP-1 Agonists in Weight Management and Their Effect on Metabolic Parameters Such as Blood Glucose, Cholesterol, and Blood Pressure.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been developed to manage type 2 diabetes mellitus. Although, in the last 10 years, the use of GLP-1 RAs, especially semaglutide and liraglutide, has increased, its clinical implications and how it affects metabolic parameters have yet to be fully consolidated. This narrative review explores the metabolic effects of GLP-1 RAs in weight management, blood glucose, cardiovascular health, lipid profiles, and blood pressure. Data were collected by comparing GLP-1 RAs, such as semaglutide, liraglutide, tripeptide, and exenatide, as well as comparing them to a baseline treatment group. GLP-1 RAs have shown consistent results in managing blood glucose levels by lowering HbA1c with minimal hypoglycemic risk and increasing insulin production and synthesis. GLP-1 RAs have been found to improve overall cardiovascular health and reduce major adverse cardiovascular events (MACE) by improving the endothelial function of the vasculature and lowering ANP (atrial natriuretic peptide) production, leading to reduced blood pressure. In addition to the cardiovascular benefits, GLP-1 RAs have a varying effect on lipid profiles, finding statistically significant results for low-density lipoprotein cholesterol levels. In conjunction with all the effects, GLP-1 RAs have been found to lower weight and aid in weight management.

Ocular adverse events associated with GLP-1 receptor agonists: a real-world study based on the FAERS database and network pharmacology

ABSTRACT Objective This study evaluates the risk of ocular adverse events (AEs) associated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) using data from the FDA Adverse Event Reporting System (FAERS) and network pharmacology methods. Methods FAERS data from 2004 to 2024 were analyzed for ocular AEs linked to GLP-1 RA treatments. Disproportionality analysis (Reporting Odds Ratio, ROR) was used to identify signals, and a drug-gene interaction network explored potential mechanisms. Results Among 17,785,793 FAERS reports, semaglutide and lixisenatide were significantly associated with ocular AEs, with RORs of 1.25 (95% CI, 1.20-1.31) and 1.96 (95% CI, 1.70-2.27), respectively. Commonly reported AEs included blurred vision, visual impairment, and diabetic retinopathy, with some AEs occurring as early as 10 days after treatment initiation. Gene enrichment analysis highlighted potential links between GLP-1-related genes and ocular AEs. Conclusion The widespread use of GLP-1 RAs has raised concerns regarding their ophthalmic safety. This study contributes new evidence from real-world data, suggesting that semaglutide and lixisenatide are associated with significant risks of ocular AEs. Further experimental studies are warranted to elucidate the underlying mechanisms and confirm these associations.

Use of Glucagon-Like Peptide-1 Receptor Agonists Does Not Increase the Risk of Cancer in Patients with Type 2 Diabetes Mellitus.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for the treatment of type 2 diabetes mellitus (T2DM) given their extra-pancreatic effects. However, there are concerns about carcinogenesis in the pancreas and thyroid gland. We aimed to evaluate the site-specific incidence of cancer in patients with T2DM-treated GLP-1 RAs using a nationwide cohort. This study included data obtained from the Korean National Health Insurance Service (between 2004 and 2021). The primary outcome was newly diagnosed cancer, and the median follow-up duration for all participants was 8 years. After propensity score matching, 7,827 participants were analyzed; 2,609 individuals each were included in the GLP-1 RA, diabetes mellitus (DM) control, and non-DM control groups. The incidence rate ratio (IRR) of subsequent cancer in patients with T2DM was 1.73, which was higher than that of individuals without DM, and it increased in both men and women. Analysis of patients with T2DM showed no increased cancer risk associated with the use of GLP-1 RA, and similar results were observed in both men and women. The IRRs of pancreatic cancer (0.74), thyroid cancer (1.32), and medullary thyroid cancer (0.34) did not significantly increase in the GLP-1 RA group compared with those in the DM control group. There was a 73% higher risk of cancer in patients with T2DM compared with the general population. However, among patients with T2DM, there was no association between the use of GLP-1 RAs and new-onset cancers, including pancreatic and medullary thyroid cancers.

The Impact of Glucagon-Like Peptide-1 Receptor Agonists on Kidney Outcomes: A Meta-Analysis of Randomized Placebo-Controlled Trials.

Key Points This is an updated meta-analysis about glucagon-like peptide-1 receptor agonists (GLP-1 RAs) incorporating findings from the recently published FLOW and SELECT studies.Our findings show that GLP-1 RAs reduce kidney disease progression in patients with type 2 diabetes or overweight/obesity status, with or without CKD.Our meta-analysis supports the use of GLP-1 RAs for reducing the risk of adverse kidney outcomes across different populations. Background Recent data indicate a potential benefit of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on the progression of kidney disease among patients with CKD. Our aim was to evaluate the effect of GLP-1 RAs on the risk of worsening kidney function across different populations. Methods We conducted a meta-analysis of randomized controlled trials that tested GLP-1 RA treatment versus placebo in individuals with type 2 diabetes or with overweight/obesity status, with or without CKD, with kidney events reported as primary or secondary end points. The primary outcome was the occurrence of worsening kidney function, defined as either a doubling of serum creatinine or a ≥40% or ≥50% decline in eGFR, according to each study report. Secondary outcomes included development of persistent macroalbuminuria and a composite of worsening kidney function or the development of persistent macroalbuminuria. Subgroup analyses were performed by eGFR and albuminuria categories. The results are presented as risk ratios with 95% confidence intervals. Results Eight trials were eligible, including a total of 68,572 patients, of whom 34,042 (49.6%) received GLP-1 RA treatment. During follow-up, 1028 participants receiving GLP-1 RA (3.0%) and 1150 participants receiving placebo (3.5%) experienced worsening kidney function. Treatment with GLP-1 RAs (versus placebo) resulted in a reduction in the risk of worsening kidney function (risk ratios, 0.84; 95% confidence interval, 0.77 to 0.91; P < 0.001). In addition, treatment with GLP-1 RAs significantly reduced the risk of developing persistent macroalbuminuria and the risk of the composite outcome of worsening kidney function or development of persistent macroalbuminuria. The results were consistent in patients with and without CKD. Conclusions In conclusion, our meta-analysis suggests that GLP-1 RA reduce kidney disease progression in type 2 diabetes or overweight/obesity regardless of CKD status.

The potential adverse effects of hypodermic glucagon-like peptide -1 receptor agoniston patients with type 2 diabetes: A population-based study.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), a class of injectable antidiabetic drugs, have shown significant efficacies in improving glycemic and weight control in patients with type 2 diabetes (T2D). However, the long-term safety of GLP-1 RAs remains insufficiently studied. This study aimed to provide real-world evidence on potential adverse outcomes associated with GLP-1 RAs use in T2D patients without major chronic diseases including impaired cardiac or renal function. We conducted a retrospective cohort study involving 7746 T2D patients on GLP-1 RAs in Shenzhen, China. They were compared with 124 371 metformin-only users and 36 146 insulin-only users, forming two therapy control groups. GLP-1 RAs users were also further 1:2 paired with the control groups. Competing risk survival analyses were conducted to assess the incidence risks, presenting subdistributional hazard ratios (sHRs) with 95% confidence intervals (CIs) for various adverse outcomes associated with GLP-1 RAs use. Compared with metformin-only users, GLP-1 RAs use was associated with increased risks of various adverse outcomes (sHRs with 95% CIs), including pancreatitis (2.01, 1.24-3.24), acute nephritis (3.20, 2.17-4.70), kidney failure (3.73, 2.74-5.08), thyroid cancer (2.25, 1.23-4.10), and thyroid dysfunction (1.27, 1.00-1.63), respectively; Similar results were also found when compared with insulin-only users. Importantly, long-term (≥12 months) GLP-1 RAs use may further elevate the incidence risks of pancreatitis, acute nephritis, thyroid cancer, and thyroid dysfunction. Compared with traditional T2D treatments, GLP-1 RAs use may be associated with increased risks of various adverse outcomes in a Chinese population. Cautions were strongly warranted in the use of GLP-1 RAs. Further validation is crucial across diverse populations.

Retrospective review of seven patients with obesity simultaneously treated with a combination of a glucagon-like peptide-1 receptor agonist and a meal replacement product

BackgroundThe use of meal replacement products (MRPs) to obtain a caloric deficit while maintaining micro- and macronutrient requirements, has a long tradition in obesity medicine. Limitations include low compliance, variability in efficacy, adverse events (related to acute changes in nutrient intake), and risk of weight regain when discontinued, and their popularity has declined after the emergence of potent GLP-1 receptor analogues (GLP1-RAs). However, GLP-1RAs have limitations, including dose-dependent risk for adverse events (AEs), high cost, as well as weight regain when discontinued. Although concomitant use of MRPs and GLP-1RAs could address some of the limitations, there is a scarcity of data reported on this. Herein we report real world clinical experience of such combined use. MethodsThis retrospective case evaluation involved people with obesity that concomitantly used MRPs (Optifast) and a GLP-1RA and were followed at one of three weight management centers in Australia or South Africa. Parameters collected were gender, age, co-morbidities, height, weight, frequency/amount of MRPs used, dose/type of GLP-1RA used, duration of combined use, and occurrence of AEs. Written informed consent for use of data was obtained from each individual, and the data were managed in an anonymized form and summarized descriptively. ResultA total of seven (5 females) individuals (mean [min, max] age 49 [30,66] years, BMI 44.8 [30.7, 57.9] kg/m2) initiated either semaglutide (n=4) or liraglutide (n=3) concomitantly with daily MRPs (starting number of servings/day 2.7 [1,6]) for a duration of 12 [4, 25] months. Change in weight/BMI/% TBW was -32.0 (-9.6, -77.8) kg/-10.3 (-3.4, -24.5) kg/m2/-24.2 %. Five individuals experienced ≥1 GLP-1RA related AE (nausea, reflux, burping, diarrhea, constipation). One individual discontinued GLP-1RA, whereas two persons discontinued the use of MRPs. ConclusionsMRPs can be initiated concomitantly with a GLP-1 RA for weight management. This might enhance weight-loss effectiveness, with potential additional benefits that should be elucidated in further and larger studies.

Risk of Esophageal and Gastric Cancer in Patients with Type 2 Diabetes Receiving Glucagon-like Peptide-1 Receptor Agonists (GLP-1 RAs): A National Analysis.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are becoming more popular in managing type 2 diabetes mellitus (T2DM). Concerns linger over potential links to malignancies like pancreatic and thyroid cancers, requiring more research to clarify their safety profiles. Additionally, evidence suggests GLP-1 RAs may lower colorectal and pancreatic cancer risk, especially in obese and overweight individuals, indicating a protective effect beyond weight loss. Current studies leave a gap in comprehensively understanding cancer risks associated with GLP-1 RAs, which prompts further research to enhance our understanding of their overall safety. We queried the US Collaborative Network (63 health care organizations) of the TriNetX research database. Patients with T2DM were identified and divided into two cohorts: patients on GLP-1 RAs and patients not on GLP-1 RAs. We excluded tobacco use and alcohol use disorders, obese patients with a body mass index (BMI) of >25 kg/m2, and those with a family history of gastrointestinal malignancy, infectious mononucleosis, chronic gastritis, pernicious anemia, helicobacter pylori infection, or gastroesophageal reflux disease (GERD). We used a 1:1 propensity score matching (PSM) model using patients' baseline characteristics, medications, labs, and genetics. We compared the rate of gastric cancer and esophageal cancer at the seven-year mark. A total of 2,748,431 patients with T2DM were identified. Of those, 6% (n = 167,077) were on a GLP-1 RA and 94% (n = 2,581,354) were not on a GLP-1 RA. After PSM, both cohorts included 146,277 patients. Patients with T2DM who were on a GLP-1 RA, compared to those who were not, had a statistically significant lower risk of both gastric cancer (0.05% vs. 0.13%, p < 0.0001) and esophageal cancer (0.04% vs. 0.13%, p < 0.0001) at the seven-year mark. The use of GLP-1 RAs in patients with T2DM does not significantly increase the risk of gastric or esophageal cancer. This finding supports the continued use of GLP-1 analogues as a therapeutic option in managing T2DM, considering their well-established benefits and low risk of complications. Based on the study results, these medications may even have a protective effect against these malignancies.

GLP-1 receptor agonists for weight loss, benefits and risks: A systematic review of the literature

Introduction: Obesity is a chronic disease linked to numerous complications. Pharmacotherapy constitutes one of the therapeutic options by which people with obesity can achieve and maintain the desired weight.Objectives: to describe the mechanism of action of glucagon-1 receptor agonists (GLP-1RAs) and their effect on weight loss and long-term weight maintenance. Methods: an information search was conducted using biomedical databases to gather relevant evidence on the efficacy and safety of GLP-1RAs in weight management. Studies addressing both initial weight loss and long-term maintenance based on the use of GLP-1RAs were analyzed.Development: GLP-1RA therapy, initially developed to treat type 2 diabetes, has been shown to be effective in reducing body weight. Daily subcutaneous administration of liraglutide has been approved, and weekly subcutaneous administration of semaglutide is being investigated in phase III trials for the management of obesity. Conclusions: consideration of GLP-1 receptor agonists as a robust therapeutic option for the management of obesity in patients who have not responded adequately to other interventions is recommended. Their use should be personalized, carefully evaluating the benefit-risk ratio for each patient. It is crucial to continue research in this field to better understand the long-term effects of GLP-1 receptor agonists

GLP-1 Receptor Agonists and Risk for Cirrhosis and Related Complications in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasing cause of cirrhosis. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are effective in improving liver inflammation in patients with MASLD. To determine whether use of GLP-1 RAs is associated with lower risk of developing cirrhosis and its complications, including decompensation and hepatocellular cancer (HCC), among patients with MASLD. This retrospective cohort study with an active comparator, new-user design used data from the national Veterans Health Administration Corporate Data Warehouse and Central Cancer Registry. Patients with MASLD and diabetes who were seen at 130 Veterans Health Administration hospitals and associated ambulatory clinics and who initiated either a GLP-1 RA or dipeptidyl peptidase 4 inhibitor (DPP-4i) between January 1, 2006, and June 30, 2022, were included. Patients were followed up from baseline until one of the study outcomes or the end of the study period (December 31, 2022), whichever came first. Each GLP-1 RA new user was propensity score matched in 1:1 ratio to a patient who initiated a DPP-4i during the same month. Separate analyses were conducted among patients without and with cirrhosis at baseline. For patients without cirrhosis, the primary outcome was progression to cirrhosis defined by validated diagnoses codes or a noninvasive marker of liver fibrosis, and secondary outcomes were cirrhosis complications defined both as a composite and individual complications, including decompensation, HCC, or liver transplant, and all-cause mortality. For patients with cirrhosis, the primary outcome was a composite outcome of cirrhosis complications, and secondary outcomes were decompensation, HCC, and all-cause mortality. Of 16 058 patients who initiated GLP-1 RAs, 14 606 did not have cirrhosis (mean [SD] age, 60.56 [10.31] years; 13 015 [89.1%] male), and 1452 had cirrhosis (mean [SD] age, 66.99 [7.09] years; 1360 [93.7%] male) at baseline. These patients were matched to an equal number of patients who initiated a DPP-4i. In patients without cirrhosis, GLP-1 RA use, compared with DPP-4i use, was associated with a lower risk of cirrhosis (9.98 vs 11.10 events per 1000 person-years; hazard ratio [HR], 0.86; 95% CI, 0.75-0.98). Similar results were seen for the secondary outcomes. GLP-1 RA use, compared with DPP-4i use, was associated with a lower risk of the composite outcome of cirrhosis complications (1.89 vs 2.55 events per 1000 person-years; HR, 0.78; 95% CI, 0.59-1.04) and mortality (21.77 vs 24.43 events per 1000 person-years; HR, 0.89; 95% CI, 0.81-0.98). There were no associations between GLP-1 RA use and outcomes in patients with cirrhosis. In this cohort study, GLP-1 RA use was associated with a lower risk of progression to cirrhosis and mortality among patients with MASLD and diabetes. The protective association was not seen in patients with existing cirrhosis, underscoring the importance of treatment earlier in the disease course.

Real-World Impact of GLP-1 Receptor Agonists on Endoscopic Patient Outcomes in an Ambulatory Setting: A Retrospective Study at a Large Tertiary Center.

Background: Glucagon-like peptide receptor agonists (GLP-1 RAs) are associated with delayed gastric emptying and may increase the risk of aspiration due to retained gastric contents. There are no guidelines on peri-endoscopic use of GLP-1 RAs, and real-world outcomes in an ambulatory setting remain unknown. This study reports real-world data from an ambulatory center associated with a large tertiary hospital. Methods: A retrospective review of electronic medical records was conducted for patients who underwent esophagogastroduodenoscopy (EGD) at a hospital-based outpatient center from January to June 2023. Exclusions included non-elective procedures, current opioid use, altered foregut anatomy, and known gastroparesis. All patients were on GLP-1 RAs before endoscopy and followed standard fasting protocols. Adverse event rates were recorded, and patients were divided into cohorts based on GLP-1 RA use. Univariate and multivariate regression analyses identified risk factors for food retention and complications. Results: A total of 1438 patients underwent elective EGD during the study period. Among the 1046 patients included, 73 (7%) were on GLP-1 RAs. The procedure was aborted in four patients (0.4%) due to gastric food retention, with two (50%) on GLP-1 RAs. Independent risk factors for food retention included GLP-1 RA use (OR: 9.19; 95% CI: 2.73-30.8; p = 0.0003) and diabetes (OR 5.6; 95% CI: 1.72-18.2; p = 0.004). Tirzepatide showed the strongest association (p = 0.0056). Factors that did not impact food retention included A1c, BMI, and gender. Protective factors were age (OR 0.96; 95% CI: 0.93-0.99; p = 0.02) and same-day colonoscopy (OR 0.18; 95% CI: 0.06-0.58; p = 0.003). Conclusions: GLP-1 RA use in diabetics increases the risk of retained gastric contents during elective EGD, particularly with tirzepatide, without increasing aspiration risk. Patients undergoing simultaneous colonoscopy had a lower risk of retained gastric contents. Further studies are needed to evaluate the impact of GLP-1 RAs on gastric food retention and procedural risk.

Evaluating Cardiovascular Benefits of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) in Type 2 Diabetes Mellitus: A Systematic Review.

Cardiovascular risks and complications remain elevated in patients with type 2 diabetes even after appropriate control of contributing factors like glycemic control, hypertension, and lipid profile. More efficient methods are needed to address this issue in type 2 diabetics. Newer drugs like glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown a cardioprotective effect in addition to glycemic control. This systematic review aims to study the latest literature findings on the cardiovascular effects of GLP-1 RAs in patients with type 2 diabetes. We used PubMed, Google Scholar, Science Direct, and Biomed Central databases for our data collection. Our review adheres to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The outcomes evaluated in the review include major adverse cardiovascular events (MACE), heart failure, stroke, all-cause mortality, and effects on cardiovascular risk factors. After careful inspection and quality check, we included 14 articles in the systematic review. GLP-1 RAs were associated with a significant reduction in cardiovascular mortality, all-cause mortality, nonfatal myocardial infarction (MI), and nonfatal stroke, especially in patients with existing cardiovascular risk factors. However, more evidence is required to determine if these benefits extend to those without such risk factors. Limited data suggest that GLP-1 RAs might have a protective effect on arrhythmias, but this area needs further investigation. Despite their potential, several barriers hinder the widespread use of GLP-1 RAs. In conclusion, GLP-1 RAs significantly reduce cardiovascular mortality, all-cause mortality, nonfatal MI, and stroke, with minor effects on hospitalization due to heart failure. Benefits are greater in patients with cardiovascular risk factors. A comprehensive, multilevel approach to policy development and implementation is necessary to optimize the use of these medications in eligible populations.

Glucagon -like Peptide 1 Receptor Agonist Use and the Effect on Diabetic Retinopathy: An Uncertain Relationship

Glucagon-like Peptide 1 Receptor Agonists (GLP-1 RAs) are a group of relatively novel medications for the treatment of diabetes mellitus. These medications can mimic the naturally occurring incretins of the body, which promote the release of insulin in response to hyperglycaemia. The anti-glycaemic effects of these medications can be profound and carry other metabolic benefits such as promoting weight loss. Clinical trials have shown GLP-1 RAs are safe to use from a cardiovascular perspective. However, some trials have suggested a link between GLP-1 RA use and worsening diabetic retinopathy. The conclusions surrounding this link are poorly established as data is drawn primarily from cardiovascular outcome trials. If an association does exist, a possible explanation might be the observed phenomenon of early worsening diabetic retinopathy with rapid correction of hyperglycaemic states. Trials which look at diabetic retinopathy as a primary outcome in relation to use of GLP-1 RAs are sparce and warrant investigation given the growing use of this group of medications. Therefore currently, it is uncertain what effect, beneficial or adverse, GLP-1 RA use has on diabetic retinopathy. This article provides an overview of GLP-1 RA use as a treatment for diabetes mellitus and the current understanding of their relationship with diabetic retinopathy.

Mortality and cardiovascular events in diabetes mellitus patients at dialysis initiation treated with glucagon-like peptide-1 receptor agonists

BackgroundGlucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) have demonstrated efficacy in improving mortality and cardiovascular (CV) outcomes. However, the impact of GLP-1RAs therapy on cardiorenal outcomes of diabetic patients at the commencement of dialysis remains unexplored.PurposeThis study aimed to investigate the long-term benefits of GLP-1RAs in type 2 diabetic patients at dialysis commencement.MethodsA cohort of type 2 diabetic patients initializing dialysis was identified from the TriNetX global database. Patients treated with GLP-1RAs and those treated with long-acting insulin (LAI) were matched by propensity score. We focused on all-cause mortality, four-point major adverse cardiovascular events (4p-MACE), and major adverse kidney events (MAKE).ResultsAmong 82,041 type 2 diabetic patients initializing dialysis, 2.1% (n = 1685) patients were GLP-1RAs users (mean ages 59.3 years; 55.4% male). 1682 patients were included in the propensity-matched group, treated either with GLP-1RAs or LAI. The main causes of acute dialysis in this study were ischemic heart disease (17.2%), followed by heart failure (13.6%) and sepsis (6.5%). Following a median follow-up of 1.4 years, GLP-1RAs uses at dialysis commencement was associated with a reduced risk of mortality (hazard ratio [HR] = 0.63, p < 0.001), 4p-MACE (HR = 0.65, p < 0.001), and MAKE (HR = 0.75, p < 0.001). This association was particularly notable in long-acting GLP-1RAs users, with higher BMI, lower HbA1c, and those with eGFR > 15 ml/min/1.73m2. GLP-1RAs’ new use at dialysis commencement was significantly associated with a lower risk of MACE (p = 0.047) and MAKE (p = 0.004). Additionally, GLP-1RAs use among those who could discontinue from acute dialysis or long-term RAs users was associated with a lower risk of mortality, 4p-MACE, and MAKE.ConclusionGiven to the limitations of this observational study, use of GLP-1RAs at the onset of dialysis was associated with a decreased risk of MACE, MAKE, and all-cause mortality. These findings show the lack of harm associated with the use of GLP-1RAs in diabetic patients at the initiation of acute dialysis.

Barriers and Strategies to Optimize the Use of Glucagon-Like Peptide 1 Receptor Agonists in People with Type 2 Diabetes and High Cardiovascular Risk or Established Cardiovascular Disease: A Delphi Consensus in Spain.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are effective for glycemic control, with many also demonstrating cardiovascular (CV) benefit, in people with type 2 diabetes (T2D). This study aimed to find a consensus on the barriers and strategies for the optimal use of GLP-1 RAs in people with T2D and high CV risk or established cardiovascular disease (CVD) in Spain. A two-round Delphi survey (53 questions) was conducted among members of four national scientific societies in Spain, including physicians experienced in the management of people with T2D. The degree of consensus was evaluated with a 7-point Likert scale, establishing consensus when≥70% of the panelists agreed (6-7) or disagreed (1-2). A total of 97 physicians participated in the first round (endocrinology: 34%, family and community medicine: 21%, internal medicine: 23%, and cardiology: 23%), and 96 in the second round. The main barriers identified were: therapeutic inertia and late use of GLP-1 RAs; lack of a comprehensive approach to CV risk; lack of knowledge on the usefulness of GLP-1 RAs in CVD prevention and treatment; and economic/administrative barriers. Strategies with a highest consensus included: the need to establish simple protocols that integrate awareness of CV risk monitoring; training professionals and patients; and the use of new technologies. Physicians identified clinical, healthcare, and economic/administrative barriers that limit the use of GLP-1 RAs in people with T2D and high CV risk or established CVD in Spain, highlighting the importance of integrating these therapies according to clinical practice guidelines.

Management of Diabetes Mellitus in Acromegaly and Cushing's Disease with Focus on Pasireotide Therapy: A Narrative Review.

Patients suffering from acromegaly and Cushing's Disease (CD) face the risk of several clinical complications. The onset of diabetes mellitus (DM) is among the most important: exposure to elevated growth hormone or cortisol levels is associated with insulin resistance (IR). DM contributes to increasing cardiovascular risk for these subjects, which is higher compared to healthy individuals. Hyperglycemia may also be caused by pasireotide, a second-generation somatostatin receptor ligand (SRLs), currently used for the treatment of these diseases. Accordingly, with 2014 medical expert recommendations, the management of hyperglycemia in patients with CD and treated with pasireotide is based on lifestyle changes, metformin, DPP-4 inhibitors (DPP-4i) and, subsequently, GLP-1 Receptor Agonists (GLP-1 RAs). There is no position for SGLT2-inhibitors (SGLT2-i). However, a very recent experts' consensus regarding the management of pasireotide-induced hyperglycemia in patients with acromegaly suggests the use of GLP-1 RAs as first line treatment (in suitable patients) and the use of SGLT2-i as second line treatment in patients with high cardiovascular risk or renal disease. As a matter of fact, beyond the hypoglycemic effect of GLP1-RAs and SGLT2-i, there is increasing evidence regarding their role in the reduction of cardiovascular risk, commonly very high in acromegaly and CD and often tough to improve despite biochemical remission. So, an increasing use of GLP1-RAs and SGLT2-i to control hyperglycemia is desirable in these diseases. Obviously, all of that must be done with due attention in order to minimize the occurrence of adverse events. For this reason, large studies are needed to analyze the presence of potential limitations.

Decreased Risk of Readmission and Complications With Preoperative GLP-1 Analog Use in Patients Undergoing Primary Total Joint Arthroplasty

BackgroundThere has been considerable interest in the use of GLP-1 receptor analogs (GLP-1 RAs) for weight optimization in patients undergoing elective arthroplasty. As there is limited data regarding the implications of their use, our study aimed to evaluate the association between preoperative GLP-1 RA use and postoperative outcomes in patients undergoing primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). MethodsThe TrinetX research network was queried to identify all patients undergoing primary THA or TKA between May 2005 and December 2023 across 84 health care organizations. Patients were stratified based on preoperative GLP-1 RA use. Propensity score matching (1:1) was performed to account for baseline differences in demographics, laboratory investigations, and comorbidities. Subsequently, risk ratios were evaluated for postoperative outcomes. ResultsA total of 268,504 and 386,356 patients underwent THA and TKA, of which 1,044 and 2,095 used preoperative GLP-1 RAs. After matching, GLP-1 RA use was associated with a decreased 90-day risk of periprosthetic joint infection (2.1 versus 3.6%, RR = 0.58, P = .042) and readmission (1.1 versus 2.0%, RR = 0.53, P = .017) following THA and TKA, respectively. There was no difference in the risk of all other outcomes between comparison groups. ConclusionsPreoperative GLP-1 RA use is associated with a 42% decreased risk of periprosthetic joint infection and 47% decreased risk of readmission in the 90-day postoperative period following THA and TKA, respectively, with no difference in other risks, including aspiration. Our findings indicate that GLP-1 RAs may be safe to use in patients undergoing elective arthroplasty; however, further studies are warranted to inform the routine use of GLP-1 RAs for weight management in THA and TKA patients.

An Assessment of Semaglutide Safety Based on Real World Data: From Popularity to Spontaneous Reporting in EudraVigilance Database

Some glucagon-like peptide-1 receptor agonists (GLP-1 RAs), first used in the treatment of type 2 diabetes mellitus (T2DM), have been approved for the treatment of obesity in patients with or without T2DM (liraglutide—LIR, semaglutide—SEM, and tirzepatide—TIR). Social media had an important influence on the off-label use of GLP-1 RAs for obesity, especially for SEM. We analyzed the Google queries related to SEM to assess people’s interest in this drug. We also investigated the occurrence of adverse drug reactions (ADRs) by searching the EudraVigilance database (EV) for Individual Case Safety Reports (ICSRs) that reported SEM as the suspected drug and performed a descriptive and a disproportionality analysis. The data obtained for SEM were compared to other GLP-1 RAs. SEM had the highest proportions of searches on Google associated with the term “weight loss” and presented the lowest number of severe ADRs, but it also had the highest number of ICSRs reported in EV. Even though no unexpected safety issues have been reported for it until now, SEM has a hi3gh tendency for overdose reports. The most frequent off-label use was reported for SEM and TIR. In order to lower the risks of ADRs, the off-label use should be reduced and carefully monitored.