Glucagon-like Peptide-1 Receptor Research Articles

The association between glucose-dependent insulinotropic polypeptide and/or glucagon-like peptide-1 receptor agonist prescriptions and substance-related outcomes in patients with opioid and alcohol use disorders: A real-world data analysis.

This study aimed to estimate the strength of association between prescriptions of glucose-dependent insulinotropic polypeptide (GIP) and/or glucagon-like peptide-1 receptor agonists (GLP-1 RA) and the incidence of opioid overdose and alcohol intoxication in patients with opioid use disorder (OUD) and alcohol use disorder (AUD), respectively. This study also aimed to compare the strength of the GIP/GLP-1 RA and substance use-outcome association among patients with comorbid type 2 diabetes and obesity. A retrospective cohort study analyzing de-identified electronic health record data from the Oracle Cerner Real-World Data. About 136 United States of America health systems, covering over 100 million patients, spanning January 2014 to September 2022. The study included 503 747 patients with a history of OUD and 817 309 patients with a history of AUD, aged 18 years or older. The exposure indicated the presence (one or more) or absence of GIP/GLP-1 RA prescriptions. The outcomes were the incidence rates of opioid overdose in the OUD cohort and alcohol intoxication in the AUD cohort. Potential confounders included comorbidities and demographic factors. Patients with GIP/GLP-1 RA prescriptions demonstrated statistically significantly lower rates of opioid overdose [adjusted incidence rate ratio (aIRR) in OUD patients: 0.60; 95% confidence interval (CI) = 0.43-0.83] and alcohol intoxication (aIRR in AUD patients: 0.50; 95% CI = 0.40-0.63) compared to those without such prescriptions. When stratified by comorbid conditions, the rate of incident opioid overdose and alcohol intoxication remained similarly protective for those prescribed GIP/GLP-1 RA among patients with OUD and AUD. Prescriptions of glucose-dependent insulinotropic polypeptide and/or glucagon-like peptide-1 receptor agonists appear to be associated with lower rates of opioid overdose and alcohol intoxication in patients with opioid use disorder and alcohol use disorder. The protective effects are consistent across various subgroups, including patients with comorbid type 2 diabetes and obesity.

Semaglutide 2.4 mg in Participants With Metabolic Dysfunction-Associated Steatohepatitis: Baseline Characteristics and Design of the Phase 3 ESSENCE Trial.

Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated potential beneficial effects in metabolic dysfunction-associated steatohepatitis (MASH). To describe the trial design and baseline characteristics of the 'Effect of Semaglutide in Subjects with Non-cirrhotic Non-alcoholic Steatohepatitis' (ESSENCE) trial (NCT04822181). ESSENCE is a two-part, phase 3, randomised, multicentre trial evaluating the effect of subcutaneous semaglutide 2.4 mg in participants with biopsy-proven MASH and fibrosis stage 2 or 3. The primary objective of Part 1 is to demonstrate that semaglutide improves liver histology compared with placebo. The two primary endpoints are: resolution of steatohepatitis and no worsening of liver fibrosis, and improvement in liver fibrosis and no worsening of steatohepatitis. The Part 2 objective is based on clinical outcomes. The current work reports baseline characteristics of the first 800 randomised participants which includes demographics, laboratory parameters, liver histology, non-invasive tests and presence of metabolic dysfunction-associated steatotic liver disease (MASLD) cardiometabolic criteria. Of 800 participants, 250 (31.3%) had fibrosis stage 2 and 550 (68.8%) had fibrosis stage 3. In the overall population, mean (standard deviation [SD]) age was 56 (11.6) years, 57.1% were female, mean (SD) body mass index was 34.6 (7.2) kg/m2, 55.5% had type 2 diabetes and > 99% had at least one MASLD cardiometabolic criterion according to the published definition. The ESSENCE baseline population includes participants with clinically significant fibrosis stages 2 and 3. Although MASLD cardiometabolic criteria were not a requirement for study enrolment, almost all participants (> 99%) had at least one MASLD cardiometabolic criterion. NCT04822181.

Glucagon-like peptide-1 receptor agonists may benefit cardiopulmonary outcomes in patients with COPD

BackgroundClinical studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1 RA) can have beneficial effects on cardiopulmonary function. We conducted this longitudinal cohort study to compare the risk of cardiopulmonary...

Facial edema and necrotic ulcers: a cutaneous reaction to liraglutide.

Due to rising obesity rates, new drugs like liraglutide, a GLP-1 receptor agonist, are increasingly used for weight loss. While liraglutide-related skin reactions are rare, this case report describes a 44-year-old male with severe facial edema and necrotic ulcers following liraglutide administration. Despite having taken the drug five years earlier without issue, the patient developed symptoms after receiving two doses. A skin biopsy revealed necrosis and inflammation, and the condition was successfully treated with steroids. The report underscores the need to consider cutaneous adverse effects in patients using liraglutide.

Validation of radiolabelled exendin for beta cell imaging by ex vivo autoradiography and immunohistochemistry of human pancreas

BackgroundEstimation of beta cell mass is currently restricted to evaluating pancreatic tissue samples, which provides limited information. A non-invasive imaging technique that reliably quantifies beta cell mass enables monitoring of changes of beta cell mass during the progression of diabetes mellitus and may contribute to monitoring of therapy effectiveness. We assessed the specificity of radiolabelled exendin for beta cell mass quantification in humans. Fourteen adults with pancreas tumours were injected with 111In-labeled exendin-4 prior to pancreatic resection. In resected pancreas tissue, endocrine-exocrine ratios of tracer uptake were determined by digital autoradiography and accumulation of 111In-labeled exendin-4 was compared to insulin and GLP-1 receptor staining. Of four participants, abdominal single photon emission computed tomography/computed tomography (SPECT/CT) images were acquired to quantify pancreatic uptake in vivoResultsTracer uptake was predominantly present in the endocrine pancreas (endocrine-exocrine ratio: 3.6 [2.8–10.8]. Tracer accumulation showed overlap with insulin-positive regions, which overlapped with GLP-1 receptor positive areas. SPECT imaging showed pancreatic uptake of radiolabelled exendin in three participants.ConclusionRadiolabelled exendin specifically accumulates in the islets of Langerhans in human pancreas tissue. The clear overlap between regions positive for insulin and the GLP-1 receptor substantiate the beta cell specificity of the tracer. Radiolabelled exendin is therefore a valuable imaging agent for human beta cell mass quantification and has the potential to be used for a range of applications, including improvement of diabetes treatment by assessment of the effects of current and novel diabetes therapies on the beta cell mass.Trial registrationClinicalTrials.gov NCT03889496, registered 26,032,019, URL https://clinicaltrials.gov/study/NCT03889496?term=NCT03889496. ClinicalTrials.gov NCT04733508, registered 02022021, URL https://clinicaltrials.gov/study/NCT04733508.

Estimating the lives that could be saved by expanded access to weight-loss drugs

Obesity is a major public health crisis in the United States (US) affecting 42% of the population, exacerbating a spectrum of other diseases and contributing significantly to morbidity and mortality overall. Recent advances in pharmaceutical interventions, particularly glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, liraglutide) and dual gastric inhibitory polypeptide and GLP-1 receptor agonists (e.g., tirzepatide), have shown remarkable efficacy in weight-loss. However, limited access to these medications due to high costs and insurance coverage issues restricts their utility in mitigating the obesity epidemic. We quantify the annual mortality burden directly attributable to limited access to these medications in the US. By integrating hazard ratios of mortality across body mass index categories with current obesity prevalence data, combined with healthcare access, willingness to take the medication, and observed adherence to and efficacy of the medications, we estimate the impact of making these medications accessible to all those eligible. Specifically, we project that with expanded access, over 42,000 deaths could be averted annually, including more than 11,000 deaths among people with type 2 diabetes. These findings underscore the urgent need to address barriers to access and highlight the transformative public health impact that could be achieved by expanding access to these novel treatments.

Combining GLP-1 receptor agonists and SGLT-2 inhibitors for cardiovascular disease prevention in type 2 diabetes: A systematic review with multiple network meta-regressions.

Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT-2I) are associated with significant cardiovascular benefit in type 2 diabetes (T2D). However, GLP-1RA or SGLT-2I alone may not improve some cardiovascular outcomes in patients with prior cardiovascular co-morbidities. To explore whether combining GLP-1RA and SGLT-2I can achieve additional benefit in preventing cardiovascular diseases in T2D. The systematic review was conducted according to PRISMA recommendations. The protocol was registered on PROSPERO (ID: 42022385007). A total of 107049 participants from eligible cardiovascular outcomes trials of GLP-1RA and SGLT-2I were included in network meta-regressions to estimate cardiovascular benefit of the combination treatment. Effect modification of prior myocardial infarction (MI) and heart failure (HF) was also explored to provide clinical insight as to when the combination treatment should be considered. The estimated hazard ratios (HR)GLP-1RA/SGLT-2I vs Placebo (0.75-0.98) and HRCombination vs GLP-1RA/SGLT-2I (0.26-0.86) for primary and secondary cardiovascular outcomes suggested that the combination treatment may achieve additional cardiovascular benefit compared with GLP-1RA or SGLT-2I alone. In patients with prior MI or HF, the mono-therapies may not improve the overall cardiovascular outcomes, as the estimated HRMI+/HF+ (0.57-1.52) suggested that GLP-1RA or SGLT-2I alone may be associated with lower risks of hospitalization for HF but not cardiovascular death. Considering its greater cardiovascular benefit in T2D, the combination treatment of GLP-1RA and SGLT-2I might be prioritized in patients with prior MI or HF, where the monotherapies may not provide sufficient cardiovascular protection.

The effect of antidiabetic drugs on bone metabolism: a concise review.

Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia, which derives from either insufficient insulin production [type 1 diabetes mellitus (T1DM)] or both impaired insulin sensitivity along with inadequate insulin production [type 2 diabetes mellitus (T2DM)] and affects millions of people worldwide. In addition to the adverse effects of DM on classical target organs and tissues, skeletal health can also be adversely affected. There is considerable evidence linking DM with osteoporosis. The fracture risk in patients with DM differs upon the type of diabetes, and it appears to be related to the type of anti-diabetic treatment. Antidiabetic drugs may have various effects on bone health. Most of them have neutral or even favorable effects on bone metabolism with the exception of thiazolidinediones (TZDs). Some studies suggest that TZDs may have negative impact on bone health by decreasing bone formation and increasing the fracture risk. There are also limited studies linking the use of canagliflozin, a Sodium-glucose contransporter-2 inhibitor (SGLT2i), with increased fracture risk. On the other hand, therapies that are based on incretin effect, like Dipeptidyl peptidase-4 inhibitors (DPP-4i) and Glucagon-like peptide-1 receptor agonizts (GLP-1RAs) might have positive effects on bone health by promoting bone formation. Herein we review the impact of antidiabetic drugs on bone health, highlighting the potential benefits and risks associated with these medications in an attempt to contribute to the development of personalized treatment strategies for individuals with DM.

Muscle Mass and Glucagon-Like Peptide-1 Receptor Agonists: Adaptive or Maladaptive Response to Weight Loss?

Recent studies have shown that pharmacologic weight loss with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and combination therapies is approaching magnitudes achieved with surgery. However, as more weight loss is achieved, there is concern for potential adverse effects on muscle quantity, composition, and function. This primer aims to address whether muscle-related changes associated with weight loss treatments such as GLP-1 RAs may be maladaptive (ie, adversely affecting muscle health or function), adaptive (ie, a physiologic response to weight loss maintaining or minimally affecting muscle health or function), or perhaps an enhanced response to weight loss (ie, improved muscle health or function after treatment). Based on contemporary evidence with the addition of studies using magnetic resonance imaging, skeletal muscle changes with GLP-1 RA treatments appear to be adaptive: changes in muscle volume z-score indicate a change in muscle volume that is commensurate with what is expected given aging, disease status, and weight loss achieved, and the improvement in insulin sensitivity and muscle fat infiltration likely contributes to an adaptive process with improved muscle quality, lowering the probability for loss in strength and function. Nevertheless, factors such as older age and prefrailty may influence the selection of appropriate candidates for these therapies because of risk for sarcopenia. Several pharmacologic treatments to maintain or improve muscle mass designed in combination with GLP-1-based therapies are under development. For future development of GLP-1-based therapies (and other therapies) designed for weight loss, as well as for patient-centered treatment optimization, the introduction of more objective and comprehensive ways of assessing muscle health (including accurate and meaningful assessments of muscle quantity, composition, function, mobility, and strength) is important for the substantial numbers of patients who will likely be taking these medications well into the future.

Surgical or medical treatment of obesity-associated type 2 diabetes-an increasing clinical conundrum

In this editorial, we comment on the article by He et al , specifically in relation to the efficacy of bariatric surgery vs glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy in the management of type 2 diabetes (T2D) associated with obesity. Bariatric surgery has now also been shown to be safe and effective in pre-teens and teenagers with obesity and T2D, but information on newer GLP-1RAs in these groups is predictably limited. In older individuals (age > 65 years), both bariatric surgery and GLP-1RA therapy improve cardiovascular outcomes. Bariatric surgery is not infrequently associated with post-operative postprandial hypoglycemia, which is not the case with GLP-1RAs and, paradoxically, there is evidence that GLP-1RAs may reduce both the frequency and severity of postprandial hypoglycemia. Comparative trials of the long-term efficacy of bariatric surgery and GLP-1RAs are indicated.

Metabolic dysfunction-associated steatotic liver disease: a narrative review of pathophysiology, diagnosis, and management

Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD) poses a significant healthcare burden, affecting approximately 38% of the global population. The rising prevalence of MASLD, particularly among younger individuals, increases the risk of severe liver complications such as cirrhosis and hepatocellular carcinoma. In this narrative review, we present a detailed examination of MASLD, previously referred to as Non-alcoholic Fatty Liver Disease(NAFLD), which is distinguished by the accumulation of excess fat in hepatocytes without the involvement of alcohol intake. We examine the multifaceted pathophysiology of MASLD, showing the interplay of metabolic, genetic, and environmental factors contributing to its development and progression. Diagnostic approaches are discussed, which show the role of non-invasive imaging techniques such as ultrasound, CT, and MRI, alongside histopathological evaluation when necessary. The review also explores the potential of biomarkers related to inflammation, fibrosis, and oxidative stress in improving diagnostic accuracy and monitoring disease progression. Management strategies for MASLD focus mainly on lifestyle adjustments, such as changes in diet, enhanced physical activity, and weight reduction, which are vital for improving liver steatosis and preventing the progression of the disease. Additionally, pharmacological treatments targeting various pathophysiological pathways, such as insulin resistance and lipid metabolism, are reviewed. Promising agents include pioglitazone, GLP-1 receptor agonists, SGLT2 inhibitors, resmetirom, FGF21 analogues, and lanifibranor. This review highlights the need for continued research into the factors influencing MASLD to develop individualized prevention and treatment strategies. By summarizing current knowledge and identifying future research directions, this narrative review aims to contribute to the better understanding and management of MASLD, ultimately reducing its global health burden.

Exploring omics signature in the cardiovascular response to semaglutide: Mechanistic insights and clinical implications.

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is a widely used drug for the treatment of type 2 diabetes that offers significant cardiovascular benefits. This review systematically examines the proteomic and metabolomic indicators associated with the cardiovascular effects of semaglutide. A comprehensive literature search was conducted to identify relevant studies. The review utilizes advanced analytical technologies such as mass spectrometry and nuclear magnetic resonance (NMR) to investigate the molecular mechanisms underlying the effects of semaglutide on insulin secretion, weight control, anti-inflammatory activities and lipid metabolism. These "omics" approaches offer critical insights into metabolic changes associated with cardiovascular health. However, challenges remain such as individual variability in expression, the need for comprehensive validation and the integration of these data with clinical parameters. These issues need to be addressed through further research to refine these indicators and increase their clinical utility. Future integration of proteomic and metabolomic data with artificial intelligence (AI) promises to improve prediction and monitoring of cardiovascular outcomes and may enable more accurate and effective management of cardiovascular health in patients with type 2 diabetes. This review highlights the transformative potential of integrating proteomics, metabolomics and AI to advance cardiovascular medicine and improve patient outcomes.

GLP-1 Receptor Agonists and the Path to Sustainable Obesity Care

This Viewpoint discusses the optimal treatment duration of glucagon-like peptide-1 receptor agonists in people with obesity and the benefits of off-ramping, the tapering of these antiobesity medications following an initial treatment period.

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.

Risk of Suicidal Ideation or Attempts in Adolescents With Obesity Treated With GLP1 Receptor Agonists

Glucagon-like peptide 1 receptor agonists (GLP1R) are increasingly being used for the treatment of obesity in adolescents. It is currently unknown whether GLP1R treatment is associated with suicidal ideation or attempts in this population. To investigate the association between GLP1R initiation and suicidal ideation or attempts in adolescents with obesity. Retrospective propensity score-matched cohort study using electronic health records from the TriNetX global federated network between December 2019 and June 2024. The analysis included data from 120 health care organizations, mainly from the USA. Participants were adolescents aged 12 to 18 years with a diagnosis of obesity and evidence of an antiobesity GLP1R prescription or lifestyle intervention without GLP1R within the following year. Cohorts were balanced for baseline demographic characteristics, psychiatric medications and comorbidities, and diagnoses associated with socioeconomic status and health care access using propensity score matching. Initial prescription of GLP1R (study cohort) or lifestyle intervention without GLP1R (control cohort). Incidence of suicidal ideation or attempts based on International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes recorded in patient electronic health records during 12 months of follow-up. Diagnoses of upper respiratory tract infections (URTI) were used as negative control outcomes, and gastrointestinal symptoms (GI) were used as positive control outcomes. A total of 4052 adolescents with obesity and a concomitant antiobesity intervention were identified for the GLP1R cohort and 50 112 were identified for the control cohort. Propensity score matching resulted in 3456 participants in each balanced cohort. Prescription of GLP1R was associated with a 33% reduced risk for suicidal ideation or attempts over 12 months of follow-up (1.45% vs 2.26%; hazard ratio [HR], 0.67; 95% CI, 0.47-0.95; P = .02) and a higher rate of GI symptoms (6.9% vs 5.4%; HR, 1.41; 95% CI, 1.12-1.78; P = .003) but no difference in rates of URTI diagnoses. In this study, adolescents with obesity prescribed a GLP1R had a lower incidence of suicidal ideation or attempts compared with matched patients not prescribed GLP1R who were treated with lifestyle intervention. These results suggest a favorable psychiatric safety profile of GLP1R in adolescents. The detected reduction in HRs for suicidal ideation among adolescents with obesity prescribed GLP1R suggests potential avenues for future research.

Molecular Insight into Obesity-Associated Nephropathy: Clinical Implications and Possible Strategies for its Management.

Obesity is a significant health concern due to its rapid increase worldwide. It has been linked to the pathogenic factors of renal diseases, cancer, cardiovascular diseases, hypertension, dyslipidemia, and type 2 diabetes. Notably, obesity raises the likelihood of developing chronic kidney disease (CKD), leading to higher adult mortality and morbidity rates. This study explores the molecular mechanisms that underlie obesity-associated nephropathy and its clinical implications. Obesity-Associated Nephropathy (OAN) develops and worsens due to insulin resistance and hyperinsulinemia, which promote renal sodium reabsorption, glomerular hyperfiltration, and hypertension, leading to progressive kidney damage. Renal damage is further aggravated by persistent inflammation and redox damage, mediated by adipokines and proinflammatory cytokines, such as TNF-α and IL-6. Furthermore, stimulation of the sympathetic nervous system and the renin-angiotensin- aldosterone system (RAAS) intensifies glomerular hypertension and fibrosis. These elements cause glomerular hyperfiltration, renal hypertrophy, and progressive kidney damage. Clinical manifestations of obesity-associated nephropathy include proteinuria, reduced glomerular filtration rate (GFR), and ultimately, CKD. Management strategies currently focus on lifestyle modifications, such as weight loss through diet and exercise, which have been effective in reducing proteinuria and improving GFR. Pharmacological treatments targeting metabolic pathways, including GLP-1 receptor agonists and SGLT2 inhibitors, have shown renoprotective properties. Additionally, traditional RAAS inhibitors offer therapeutic benefits. Early detection and comprehensive management of OAN are essential to prevent its progression and lessen the burden of CKD.

Glucagon and glucagon-like peptide-1 dual agonist therapy: A possible future towards fatty kidney disease.

Obesity is a growing epidemic affecting approximately 40% of the adult population in developed countries with major health consequences and comorbidities, including diabetes mellitus and insulin resistance, metabolically associated fatty liver disease, atherosclerotic cardiovascular and cerebrovascular diseases and chronic kidney disease. Pharmacotherapies targeting significant weight reduction may have beneficial effects on such comorbidities, though such therapeutic options are highly limited. In this narrative review, we aim to evaluate current knowledge regarding dual agonist therapies and potential implications for managing fatty kidney and chronic kidney disease. Glucagon-like peptide-1 agonists and sodium-glucose cotransporter-2 inhibitors are two novel classes of glucose-lowering medications with potential implications and beneficiary effects on renal outcomes, including estimated glomerular filtration rate, albuminuria and chronic kidney disease progression. Recently, dual agonist therapies targeting glucagon-like peptide-1 and glucagon receptors, namely survodutide and cotadutide, have been evaluated in managing metabolically associated fatty liver disease, a well-established example of visceral obesity. Fatty kidney is another novel concept implicated in the pathophysiology of chronic kidney disease among patients with visceral obesity.

Semaglutide Treatment Effects on Liver Fat Content in Obese Subjects with Metabolic-Associated Steatotic Liver Disease (MASLD)

Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) represents a major clinical complication of obesity. Methods: In this study, we used magnetic resonance (MR) methods to determine the effect of obesity treatment with semaglutide, a GLP-1 receptor agonist, on the liver fat content and selected metabolic variables. We investigated whether treatment would affect the acute response of liver fat to glucose and fructose administration and whether it would affect the fatty acid profile of VLDL-triglycerides. Sixteen obese non-diabetic men underwent a 16-week dietary intervention and 16-week treatment with subcutaneous semaglutide in a crossover design without a washout period. The order of the interventions was randomized. Results: After treatment, body weight of the subjects decreased by 5% and liver fat by a third, whereas dietary intervention had no impact on these parameters. The decrease in liver fat with semaglutide did not correlate with changes in body weight and other measures of adiposity and was unrelated to improved insulin sensitivity. Conclusions: The proportion of palmitic and palmitoleic acids in VLDL-triglycerides decreased after treatment, suggesting that the beneficial effects of semaglutide on liver fat are mediated by the suppression of de novo lipogenesis.

Efficacy and Safety of GLP-1 Receptor Agonists in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Efficacy and Safety of GLP-1 Receptor Agonists in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Semaglutide effects on safety and cardiovascular outcomes in patients with overweight or obesity: a systematic review and meta-analysis.

Semaglutide is a GLP-1 receptor agonist that provides a reduction in glycated hemoglobin and weight. The objective was to evaluate whether the use of semaglutide, in individuals with overweight or obesity, reduces cardiovascular outcomes and adverse effects (AE). The data bases Pubmed, Lilacs, Scielo, Scopus, Web of Science and Cochrane Library were surveyed. Initially, 3333 articles were found, of which 19 articles were included. An additional search included 19 studies, totaling 38 articles. Relative risk (RR) values were significant for hospitalization due to heart failure (HF) 0.24 95% CI 0.12-0.57 (n = 2; 1045 participants; I² = 0.18), death due to cardiovascular causes 0.83 95% CI 0.71-0.98 (n = 3; 24 084 participants; I² = 0.21), death from any cause 0.79 95% CI 0.70-0.89 (n = 3; 24 084 participants; I² = 0.07), coronary revascularization 0.76 95% CI 0.69-0.85 (n = 2;20 951 participants; I² = 0.41), and non-fatal myocardial infarction 0.76 95%CI 0.66-0.88 (n = 3; 24 084 participants; I² = 0.21), with a difference between the subgroups (p = 0.05), favoring the subcutaneous administration route. The RR of stroke was 0.65 95% CI 0.44-0.97 for patients with diabetes (n = 2; 6480 participants; I² = 0.66). There was no difference between the frequency of constipation and routes of administration, as well as between doses of oral semaglutide. The RR of adverse effects was only not significant for discontinuation of treatment for oral semaglutide. The use of semaglutide reduced 76% in hospitalization due to HF, 17% deaths due to cardiovascular causes, 21% deaths due to any cause, 24% non-fatal myocardial infarction, 24% coronary revascularization and 35% stroke (in patients with diabetes). The use of semaglutide was associated with a higher relative risk and frequency of most adverse effects evaluated.