Peri-operative Complications from Semaglutide Use

BackgroundWe performed a systematic overview of the cost-effectiveness analyses (CEAs) comparing Non-insulin antidiabetic drugs (NIADs) with other NIADs for the treatment of type 2 diabetes mellitus (T2DM), using decision-analytical modelling (DAM), focusing on both the economic results and the underlying methodological choices.MethodsEligible studies were CEAs using DAM to compare NIADs within the glucagon-like peptide-1 (GLP1) receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, or dipeptidyl peptidase-4 (DPP4) inhibitor classes with other NIADs within those classes for the treatment of T2DM. The PubMed, Embase and Econlit databases were searched from 1 January 2018 to 15 November 2022. Two reviewers screened the studies for relevance by titles and abstracts and then for eligibility via full-text screening, extracted the data from the full texts and appendices, and then stored the data in a spreadsheet.ResultsThe search yielded 890 records and 50 studies were eligible for inclusion. The studies were mainly based on a European setting (60%). Industry sponsorship was found in 82% of studies. The CORE diabetes model was used in 48% of the studies. GLP1 and SGLT2 products were the main comparators in 31 and 16 studies, respectively, while one study had DPP4 and two had no easily discernible main comparator. Direct comparison between SGLT2 and GLP1 occurred in 19 studies. At a class level, SGLT2 dominated GLP1 in six studies and was cost effective against GLP1 once as part of a treatment pathway. GLP1 was cost effective in nine studies and not cost effective against SGLT2 in three studies. At a product level, oral and injectable semaglutide, and empagliflozin, were cost effective against other within-class products. Injectable and oral semaglutide were more frequently found cost effective in these comparisons, with some conflicting results. Most of the modelled cohorts and treatment effects were sourced from randomised controlled trials. The following model assumptions varied depending on the class of the main comparator: choice of and reasoning behind risk equations, the time until the treatment switch, and how often the comparators were discontinued. Diabetes-related complications were emphasised on par with quality-adjusted life-years as model outputs. The main quality issues were regarding the description of alternatives, the perspective of analysis, the measurement of costs and consequences, and patient subgroups.ConclusionThe included CEAs using DAMs have limitations that hinder their ability to inform decision makers on the cost-effective choice: lack of updated reasoning behind the choice of key model assumptions, over-reliance on risk equations based on older treatment practices, and sponsorship bias. The question of which NIAD is cost effective for the treatment of which T2DM patient is a pressing one and the answer remains unclear.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40273-023-01268-5.

An Albumin-Exendin-4 Conjugate Engages Central and Peripheral Circuits Regulating Murine Energy and Glucose Homeostasis

New Medications for the Treatment of Diabetes

ObjectiveTo evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk.DesignNetwork meta-analysis.Data sourcesMedline, Embase, and Cochrane CENTRAL...

New Glucose-Lowering Agents for Diabetic Kidney Disease.

Time to Follow the Evidence: Glycemic Control and Cardiovascular Benefits of New Diabetes Medications

Spinal fusion is a widely performed surgical procedure for treating various spinal disorders, with lumbar fusion showing remarkably rapid growth worldwide. Despite positive outcomes after the procedure, it carries significant complications, most notably pseudarthrosis. Compromised blood supply is a key factor disrupting normal bone fusion, making optimal vascularization crucial for successful outcomes. Glucagon-like peptide-1 (GLP-1) receptor agonists, primarily used for diabetes management, demonstrate promising effects including enhanced glycemic control, improved vascular endothelial function, and direct enhancement of osteoblastic cell activity through GLP-1 receptors on bone precursor cells. Theoretically, GLP-1 receptor agonists should be beneficial for optimizing spinal fusion outcomes. We aim to systematically review and analyze the current evidence on the efficacy and safety of GLP-1 receptor agonists in promoting bone fusion and reducing complications in patients undergoing spinal fusion surgery.We conducted a comprehensive systematic review following Cochrane guidelines. We searched PubMed, Web of Science, Scopus, Embase, and Cochrane Library for studies examining GLP-1 receptor agonists in spinal fusion procedures. We used the Newcastle-Ottawa Scale for the quality assessment of the included studies. We conducted a statistical analysis using RevMan 5.4 with risk ratios for dichotomous outcomes.In total, 11 studies with a total of 14,344 participants were analyzed. GLP-1 receptor agonists significantly reduced pseudoarthrosis at six months (risk ratio (RR) = 0.63, 95% confidence interval (CI) = 0.54-0.74) and 12 months (RR = 0.64, 95% CI = 0.57-0.72), and significantly increased acute kidney injury (RR = 1.30, 95% CI = 1.03-1.65). No significant differences were observed for pseudoarthrosis at 24 months (RR = 1.03, 95% CI = 0.53-2.03), readmission rates (RR = 0.85, 95% CI = 0.48-1.51), cerebrovascular accidents (RR = 1.01, 95% CI = 0.63-1.62), and deep vein thrombosis (RR = 1.16, 95% CI = 0.78-1.72). Additionally, no significant reoperations or adverse effects were found. We also performed a subgroup analysis considering the diabetic stage, which showed valuable insights.GLP-1 receptor agonists showed promising results in reducing pseudoarthrosis at short- to medium-term follow-up, indicating potential therapeutic benefits in bone healing applications. However, the increased risk of acute kidney injury suggests the need for careful patient monitoring and risk stratification. The lack of sustained benefit at 24 months and significant heterogeneity observed in several outcomes indicate that further investigation is warranted. Future research should focus on conducting larger, well-designed randomized controlled trials with standardized outcome definitions, longer follow-up periods, and comprehensive safety monitoring to establish optimal dosing protocols and patient selection criteria for GLP-1 receptor agonist therapy in orthopedic applications.

BackgroundThe cardiovascular effects of glucagon-like peptide-1 (GLP-1) receptor agonists are still controversial in the treatment of type 2 diabetes mellitus (T2DM) patients. The purpose of this study was to evaluate the risk of cardiovascular events of GLP-1 (albiglutide, exenatide, liraglutide, semaglutide, lixisenatide and dulaglutide) receptor agonists in T2DM patients.MethodsPubMed and Embase were searched to find relevant randomized controlled trials (RCTs) from inception to June 2019 that evaluated the effect of GLP-1 receptor agonists on cardiovascular events in patients with T2DM. The T2DM patients of all the eligible trials received either GLP-1 therapy or placebo, and the cardiovascular outcomes included death from cardiovascular causes, fatal or non-fatal myocardial infarction and fatal or non-fatal stroke.ResultsWe included 6 multinational double-blind randomized placebo-control trials that included a total of 52821 T2DM patients. The results indicated that GLP-1 receptor agonists reduced the risk of death from cardiovascular causes (RR: 0.90; 95% CI: 0.83–0.97; P = 0.004) and fatal or non-fatal stroke (RR: 0.85; 95% CI: 0.77–0.94; P = 0.001) compared with the placebo controls. But GLP-1 receptor agonists did not significantly alter the fatal or non-fatal myocardial infarction compared with the placebo (RR: 0.91; 95% CI: 0.82 – 1.01; P = 0.06).ConclusionWe concluded that GLP-1 receptor agonist therapy could reduce the risk of death from cardiovascular causes and fatal or non-fatal stroke compared with the placebo in the treatment of T2DM patients in trials with cardiovascular outcomes.

Lung cancer (LC) is the second most common cancer and the leading cause of cancer deaths in the U.S. Insulin therapy, a key treatment for managing Type 2 Diabetes Mellitus (T2DM), may increase LC risk. The impact of non-insulin antidiabetic drugs, particularly GLP-1 receptor agonists (GLP-1RAs), on LC risk is not well understood. This study evaluated LC risk in T2DM patients comparing seven non-insulin antidiabetic agents to insulin. Using the TriNetX Analytics platform, we analyzed de-identified electronic health records of 1,040,341 T2DM patients treated between 2005-2019, excluding those with prior antidiabetic use or LC diagnoses. We calculated hazard ratios and confidence intervals for LC risk and used propensity score matching to control for confounding factors. All non-insulin antidiabetic drugs, except alpha-glucosidase inhibitors, significantly reduced LC risk compared to insulin, with GLP-1RAs showing the greatest reduction (HR: 0.49, 95% CI: 0.41, 0.59). GLP-1RAs were consistently associated with lowered LC risk across all histological types, races, genders, and smoking statuses. These findings suggest that non-insulin antidiabetic drugs, particularly GLP-1RAs, may be preferable for managing T2DM while reducing LC risk.

Lung cancer (LC) is the second most common cancer and the leading cause of cancer deaths in the U.S. Insulin therapy, a key treatment for managing Type 2 Diabetes Mellitus (T2DM), is associated with increased LC risk. The impact of non-insulin antidiabetic drugs, particularly GLP-1 receptor agonists (GLP-1RAs), on LC risk is not well understood. This study evaluated LC risk in T2DM patients, comparing seven non-insulin antidiabetic agents to insulin. Using the TriNetX Analytics platform, we analyzed the de-identified electronic health records of 1,040,341 T2DM patients treated between 2005 and 2019, excluding those with prior antidiabetic use or LC diagnoses. We calculated hazard ratios and confidence intervals for LC risk and used propensity score matching to control for confounding factors. All non-insulin antidiabetic drugs, except alpha-glucosidase inhibitors, were associated with significantly reduced LC risk compared to insulin, with GLP-1RAs showing the greatest reduction (HR: 0.49, 95% CI: 0.41, 0.59). GLP-1RAs were consistently associated with lowered LC risk across all histological types, races, genders, and smoking statuses. These findings suggest that non-insulin antidiabetic drugs, particularly GLP-1RAs, may be preferable for managing T2DM while reducing LC risk.

ObjectivesTo evaluate the comparative effectiveness of sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors in preventing hyperkalemia in people with type 2 diabetes in...

The incretin system plays an important role in glucose homeostasis, largely through the actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Unlike GIP, the actions of GLP-1 are preserved in patients with type 2 diabetes mellitus, which has led to the development of injectable GLP-1 receptor (GLP-1R) agonists and oral dipeptidyl peptidase-4 (DPP-4) inhibitors. GLP-1R agonists—which can be dosed to pharmacologic levels—act directly upon the GLP-1R. In contrast, DPP-4 inhibitors work indirectly by inhibiting the enzymatic inactivation of native GLP-1, resulting in a modest increase in endogenous GLP-1 levels. GLP-1R agonists generally lower the fasting and postprandial glucose levels more than DPP-4 inhibitors, resulting in a greater mean reduction in glycated hemoglobin level with GLP-1R agonists (0.4%–1.7%) compared with DPP-4 inhibitors (0.4%–1.0%). GLP-1R agonists also promote satiety and reduce total caloric intake, generally resulting in a mean weight loss of 1 to 4 kg over several months in most patients, whereas DPP-4 inhbitors are weight-neutral overall. GLP-1R agonists and DPP-4 inhibitors are generally safe and well tolerated. The glucose-dependent manner of stimulation of insulin release and inhibition of glucagon secretion by both GLP-1R agonists and DPP-4 inhibitors contribute to the low incidence of hypoglycemia. Although transient nausea occurs in 26% to 28% of patients treated with GLP-1R agonists but not DPP-4 inhibitors, this can be reduced by using a dose-escalation strategy. Other adverse events (AEs) associated with GLP-1R agonists include diarrhea, headache, and dizziness. The main AEs associated with DPP-4 inhibitors include upper respiratory tract infection, nasopharyngitis, and headache. Overall, compared with other therapies for type 2 diabetes mellitus with similar efficacy, incretin-based agents have low risk of hypoglycemia and weight gain. However, GLP-1R agonists demonstrate greater comparative efficacy and weight benefit than DPP-4 inhibitors.

ObjectiveSeveral glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1Ra) have been made recently available in Spain for type 2 diabetes mellitus (DM2) treatment. There are no published data on the clinical and...

Advances in the management of diabetes mellitus have come a long way in the 21st century. One of the most important developments in diabetes management has been the discovery of...

Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) have been used to treat patients with type 2 diabetes mellitus (T2DM) since exenatide, the first GLP-1RA, was approved in 2005. GLP-1 is a peptide hormone secreted by L cells of the small intestine in response to nutrients. GLP-1 presents a glucose-lowering effect via their insulinotropic action on pancreatic β-cells. In addition to their insulinotropic effect, GLP-1 also has pleiotropic actions associated with clinical benefits. GLP-1RAs are a well-established effective treatment for patients with T2DM. GLP-1RAs have antihyperglycemic effects with a low risk of hypoglycemia and reduce body weight. Additionally, GLP-1RAs have beneficial effects on cardiovascular risk factors, such as blood pressure and lipid levels. Large randomized cardiovascular outcome trials and meta-analyses demonstrated that GLP-1RAs reduce cardiovascular disease in T2DM patients. GLP-1RAs are recommended as part of glucose-lowering regimens in patients with T2DM and established cardiovascular disease, or those at high risk. Renal protective and beneficial effects of GLP-1RAs on nonalcoholic fatty liver disease have also been suggested.