ABSTRACT
BACKGROUND: The evident influence of GLP-1 agonists as semaglutide on gastric emptying even in adherence to recommended fasting protocols instigates debates. OBJECTIVE: To investigate the effect of semaglutide on gastric content by gastric ultrasonography in volunteers. SETTING: Private hospital. METHODS: The present study is an observational, cross-sectional, and single-center study. We included 30 consecutive volunteers aged ≥18 years who had undergone a minimum fasting period of 8 hours for solid foods and 2 hours for clear, residue-free liquids. The intervention group consisted of 15 volunteers who had used semaglutide within the last 7 days, whereas the control group consisted of 15 volunteers who had never used semaglutide. The main objective was to determine whether the stomach was full or not. RESULTS: Between June 2023 and August 2023, a total of 30 adult volunteers were included in the study, and no participant was excluded. The semaglutide group exhibited a higher prevalence of full stomach (11 of 15 [73%] versus 1 of 15 [7%], P < .001; adjusted to age P = .003). The semaglutide group also exhibited a higher prevalence of early satiety (10 of 15 [67%] versus 0 of 15 [0%], P < .001), loss of appetite (10 of 15 [67%] versus 0 of 15 [0%], P < .001), gastric fullness (8 of 15 [53%] versus 0 of 15 [0%], P = .002), and nausea (7 of 15 [47%] versus 1 of 15 [7%], P = .035). Additionally, there is no case in the semaglutide group with no gastric contents. CONCLUSIONS: The use of semaglutide is associated with full stomach even after appropriate overnight fasting. Semaglutide is also associated with increased gastrointestinal symptoms such as loss of appetite, early satiety, gastric fullness, and nausea.
ABSTRACT
Newly conducted research suggests that metabolic disorders, like diabetes and obesity, play a significant role as risk factors for psychiatric disorders. This connection presents a potential avenue for creating novel antidepressant medications by repurposing drugs originally developed to address antidiabetic conditions. Earlier investigations have shown that GLP-1 (Glucagon-like Peptide-1) analogs exhibit neuroprotective qualities in various models of neurological diseases, encompassing conditions such as Alzheimer's disease, Parkinson's disease, and stroke. Moreover, GLP-1 analogs have demonstrated the capability to enhance neurogenesis, a process recognized for its significance in memory formation and the cognitive and emotional aspects of information processing. Nonetheless, whether semaglutide holds efficacy as both an antidepressant and anxiolytic agent remains uncertain. To address this, our study focused on a mouse model of depression linked to type 2 diabetes induced by a High Fat Diet (HFD). In this model, we administered semaglutide (0.05 mg/Kg intraperitoneally) on a weekly basis to evaluate its potential as a therapeutic option for depression and anxiety. Diabetic mice had higher blood glucose, lipidic profile, and insulin resistance. Moreover, mice fed HFD showed higher serum interleukin (IL)-1ß and lipopolysaccharide (LPS) associated with impaired humor and cognition. The analysis of behavioral responses revealed that the administration of semaglutide effectively mitigated depressive- and anxiety-like behaviors, concurrently demonstrating an enhancement in cognitive function. Additionally, semaglutide treatment protected synaptic plasticity and reversed the hippocampal neuroinflammation induced by HFD fed, improving activation of the insulin pathway, demonstrating the protective effects of semaglutide. We also found that semaglutide treatment decreased astrogliosis and microgliosis in the dentate gyrus region of the hippocampus. In addition, semaglutide prevented the DM2-induced impairments of pro-opiomelanocortin (POMC), and G-protein-coupled receptor 43 (GPR43) and simultaneously increased the NeuN + and Glucagon-like Peptide-1 receptor (GLP-1R+) neurons in the hippocampus. Our data also showed that semaglutide increased the serotonin (5-HT) and serotonin transporter (5-HTT) and glutamatergic receptors in the hippocampus. At last, semaglutide changed the gut microbiota profile (increasing Bacterioidetes, Bacteroides acidifaciens, and Blautia coccoides) and decreased leaky gut, improving the gut-brain axis. Taken together, semaglutide has the potential to act as a therapeutic tool for depression and anxiety.
Subject(s)
Anxiety , Brain-Gut Axis , Cognitive Dysfunction , Depression , Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Glucagon-Like Peptides , Mice, Inbred C57BL , Animals , Glucagon-Like Peptides/pharmacology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/psychology , Diabetes Mellitus, Type 2/metabolism , Mice , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/prevention & control , Cognitive Dysfunction/etiology , Cognitive Dysfunction/metabolism , Depression/drug therapy , Depression/psychology , Depression/metabolism , Male , Anxiety/drug therapy , Anxiety/psychology , Anxiety/etiology , Gastrointestinal Microbiome/drug effects , Brain-Gut Axis/drug effects , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/psychology , Diabetes Mellitus, Experimental/metabolism , Disease Models, Animal , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic useABSTRACT
Background: The anti-inflammatory effect could be one of the mechanisms by which semaglutide reduces cardiovascular risk in patients with type 2 diabetes mellitus (T2DM) and/or obesity. Determining the anti-inflammatory effect of semaglutide was the objective of this systematic review and meta-analysis. Methods: This meta-analysis was performed according to the PRISMA guidelines. A literature search was performed to detect randomised clinical trials that have quantified the effect of semaglutide on C-reactive protein (CRP) levels compared to placebo or a control group (other glucose-lowering drugs). The primary outcome was CRP index (final CRP/basal CRP). A random-effects model was used. Results: Thirteen randomised clinical trials were considered eligible (n = 26,131). Overall, semaglutide therapy was associated with lower CRP index values compared to the placebo group (SMD -0.56; 95% CI -0.69 to -0.43, I 2 92%) or the control group (SMD -0.45; 95% CI -0.68 to -0.23, I 2 82%).Such an association was similarly observed when different treatment regimens (subcutaneous vs. oral) or different populations (patients with or without T2DM) were analysed. The sensitivity analysis showed that the results were robust. Conclusion: The present meta-analysis demonstrated that the use of semaglutide was associated with a reduction in inflammation irrespective of the population evaluated or the treatment regimen used. These findings would explain one of the mechanisms by which semaglutide reduces cardiovascular events. Systematic Review Registration: PROSPERO [CRD42024500551].
ABSTRACT
INTRODUCTION: Leukocytoclastic vasculitis (LCV) is a small vessel vasculitis involving arterioles, capillaries and postcapillary venules. LCV is generally confined to the skin, with extracutaneous manifestations occurring less frequently. LCV has multiple potential etiologies. Indeed, histological LCV can be found in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, immune complex vasculitis, vasculitis associated with systemic diseases (i.e. sarcoidosis, Sjögren's syndrome, rheumatoid arthritis, and systemic lupus erythematosus), or in vasculitis associated with cancer, infections, sepsis and use of certain medications. LCV can also be idiopathic in up to 50% of cases. CASE REPORT: Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist used for management of type 2 diabetes mellitus (T2DM), obesity and overweight associated with one or more weight-related comorbidities. A case of drug-induced LCV has already been described with the use of once-daily oral semaglutide. Herein, we describe the first case of skin-limited LCV induced by once-weekly subcutaneous semaglutide in a 73-year-old man with T2DM, who experienced the complete resolution of the skin lesions shortly after the discontinuation of semaglutide therapy. CONCLUSION: Future prospective studies, adverse event reporting and post-marketing surveillance will certainly contribute to establishing if LCV represents a less rare than expected side effect of both oral and subcutaneous semaglutide formulations.
Subject(s)
Diabetes Mellitus, Type 2 , Glucagon-Like Peptides , Vasculitis, Leukocytoclastic, Cutaneous , Humans , Male , Glucagon-Like Peptides/adverse effects , Glucagon-Like Peptides/administration & dosage , Aged , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/complications , Vasculitis, Leukocytoclastic, Cutaneous/chemically induced , Vasculitis, Leukocytoclastic, Cutaneous/drug therapy , Vasculitis, Leukocytoclastic, Cutaneous/pathology , Injections, Subcutaneous , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/administration & dosageABSTRACT
Obesity, a chronic global health problem, is associated with an increase in various comorbidities, such as cardiovascular disease, type 2 diabetes mellitus, hypertension, and certain types of cancer. The increasing global prevalence of obesity requires research into new therapeutic strategies. Glucagon-like peptide-1 receptor agonists, specifically semaglutide and liraglutide, designed for type 2 diabetes mellitus treatment, have been explored as drugs for the treatment of obesity. This minireview describes the molecular mechanisms of semaglutide and liraglutide in different metabolic pathways, and its mechanism of action in processes such as appetite regulation, insulin secretion, glucose homeostasis, energy expenditure, and lipid metabolism. Finally, several clinical trial outcomes are described to show the safety and efficacy of these drugs in obesity management.
ABSTRACT
INTRODUCTION: Type 2 diabetes is a prevalent condition. The change in glucose control and body weight with the use of once-weekly semaglutide was evaluated in individuals with Type 2 diabetes in Colombia. METHODS: This was a real-world, multi-centre, single-arm study involving adults in Colombia with Type 2 diabetes treated with once-weekly subcutaneous semaglutide for approximately 26 weeks. The primary endpoint assessed the change in glycated hemoglobin (HbA1c) from baseline to end of study. Secondary endpoints included changes in body weight from baseline to end of study. The study also explored the proportion of participants achieving predefined HbA1c targets and weight-loss responses at the end of the study. RESULTS: Data from 225 patients across 11 centers were collected. Most patients were women (65%), and the mean age of the population was 57 years with a median HbA1c of 7.6% and a median body weight of 86 kg. After approximately 26 weeks, semaglutide was associated with a significant reduction in HbA1c of - 0.88 and a body weight reduction of - 4.04kg. The proportion of patients with HbA1c < 7% increased from 32 to 66% at end of study. CONCLUSION: Patients treated with once-weekly semaglutide experienced a clinically significant reduction in HbA1c and body weight. These results are in line with previous clinical trials.
ABSTRACT
Purpose: Diabetes is a public health problem that requires strategies to impact glycemic control and reduce the risk of long-term medical complications. Pharmacological management is a necessary treatment for this disease. Therefore, semaglutide is an essential tool to achieve the treatment targets. The present study aimed to evaluate the semaglutide effects on a cohort with type 2 diabetes mellitus (T2DM) in Colombia. Materials and Methods: The cohort included 49 patients with T2DM that have been treated in a specialized care center. Their glycemic outcomes, weight, renal function, and adverse events were evaluated through a 3-, 6- and 12-month follow-up. Results: Significant differences were observed in the outcome evaluation: reduction of glycated hemoglobin levels (MD -2.74 CI -1.95 to -3.52 in 6 months), fasting plasma glucose levels, body weight (MD -7.11 CI -5.97 to -8.24), and the albumin-to-creatinine ratio. The results were maintained throughout the treatment period. The adverse event rate was 16.3%, predominating gastrointestinal events. Conclusion: This real-world evidence shows the efficacy of semaglutide in achieving treatment goals in patients with T2DM.
ABSTRACT
Obesity is a chronic, recurring, progressive disease and a major public health problem associated with several other diseases that lead to disability, morbidity, and mortality. The prevalence of obesity has increased at pandemic levels, along with increasing weight-related comorbidities and deaths worldwide. Lifestyle interventions alone provide clinically significant long-term weight loss in only a small proportion of individuals, and bariatric surgery is not suitable or desirable for all patients. Historically, anti-obesity medications achieved a mean efficacy with weight loss between 5 and 10%, which significantly impacted several comorbidities and risk factors, but the average efficacy of these medications remained lower than that expected by both patients and health care professionals and eventually curbed long-term use. Moreover, there is no direct evidence on the impact of anti-obesity medications on cardiovascular outcomes. Semaglutide is a newer anti-obesity medication that changes the overall landscape, as phase 3 studies show a mean weight loss near the 15% threshold and significant proportions of patients with a weight loss of greater than 20%. In this review, we focus on the currently available anti-obesity medications, discuss the results of semaglutide, and present perspectives on the future of obesity treatment after semaglutide.
ABSTRACT
Background: Type 2 Diabetes Mellitus (T2DM) is a highly prevalent disease worldwide and in Colombia, representing one of the main causes of death and placing a considerable burden on healthcare systems. 13 classes of drugs are approved for the treatment of T2DM, with Glucagon-like Peptide-1 (GLP-1) receptor agonists being a first-line treatment option for patients with or at high risk of certain cardiovascular diseases and chronic kidney disease. The objective of this study is to conduct a short-term cost-effectiveness analysis of once-weekly semaglutide versus once-weekly dulaglutide in Colombian adults with T2DM, from a third-party payer perspective. Methods: Numbers needed to treat were calculated for different single and composite endpoints of the SUSTAIN 7 trial, annual costs for once weekly semaglutide 1.0 mg and dulaglutide 1.5 mg were extracted from the public SISMED database. With these inputs a cost of control model was developed, to obtain the annual cost of bringing one T2DM patient to relevant clinical outcomes by using semaglutide or dulaglutide. Results: Semaglutide was considered cost-effective compared to dulaglutide across all pre-specified endpoints, even in the different scenarios evaluated in the sensitivity analyses, and in a particularly pronounced manner for weight loss outcomes. Semaglutide at a dose of 1.0 mg once-weekly was cost-effective compared to dulaglutide 1.5 mg across all outcomes in the short-term, making it an appropriate first-line choice in the treatment of T2DM when deciding between these two GLP-1 receptor agonists. Conclusions: This is the first short-term cost-effectiveness study of semaglutide and dulaglutide in T2DM Colombian patients. Our modeled results suggest that once-weekly semaglutide represents a cost-effective option for treating individuals with T2DM in Colombia who are not achieving glycaemia control with metformin, and it would be expected to improve HbA1C, promote greater weight loss and reduce costs from a third-payer perspective compared with treatment with dulaglutide.
Subject(s)
Diabetes Mellitus, Type 2 , Hypoglycemic Agents , Adult , Humans , Colombia , Cost-Effectiveness Analysis , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Weight Loss , Clinical Trials as TopicABSTRACT
Glucagon-like peptide one-receptor agonists (GLP-1 RA) are drugs that differ in their pharmacological composition and homology to human GLP-1 and are used most frequently for the treatment of type 2 diabetes and weight loss. There are isolated reports of eosinophilic adverse reactions associated with GLP-1 RA. We present the case of a 42-year-old female patient who, after starting weekly subcutaneous semaglutide, developed eosinophilic fasciitis with favorable clinical evolution after the discontinuation of semaglutide and the initiation of immunosuppression. A review of the eosinophilic adverse events that have been previously reported with GLP-1 RA is provided.
Subject(s)
Diabetes Mellitus, Type 2 , Female , Humans , Adult , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/adverse effects , Glucagon-Like Peptide Receptors , Eosinophils , Glucagon-Like Peptide 1/therapeutic useABSTRACT
STUDY OBJECTIVE: Semaglutide is a long-acting glucagon-like peptide-1 receptor agonist used for management of type 2 diabetes and/or obesity. To test the hypothesis that perioperative semaglutide use is associated with delayed gastric emptying and increased residual gastric content (RGC) despite adequate preoperative fasting, we compared the RGC of patients who had and had not taken semaglutide prior to elective esophagogastroduodenoscopy. The primary outcome was the presence of increased RGC. DESIGN: Single-center retrospective electronic chart review. SETTING: Tertiary hospital. PATIENTS: Patients undergoing esophagogastroduodenoscopy under deep sedation/general anesthesia between July/2021-March/2022. INTERVENTIONS: Patients were divided into two (SG = semaglutide, NSG = non-semaglutide) groups, according to whether they had received semaglutide within 30 days prior to the esophagogastroduodenoscopy. MEASUREMENTS: Increased RGC was defined as any amount of solid content, or > 0.8 mL/Kg (measured from the aspiration/suction canister) of fluid content. MAIN RESULTS: Of the 886 esophagogastroduodenoscopies performed, 404 (33 in the SG and 371 in the NSG) were included in the final analysis. Increased RGC was observed in 27 (6.7%) patients, being 8 (24.2%) in the SG and 19 (5.1%) in the NSG (p < 0.001). Semaglutide use [5.15 (95%CI 1.92-12.92)] and the presence of preoperative digestive symptoms (nausea/vomiting, dyspepsia, abdominal distension) [3.56 (95%CI 2.2-5.78)] were associated with increased RGC in the propensity weighted analysis. Conversely, a protective [0.25 (95%CI 0.16-0.39)] effect against increased RGC was observed in patients undergoing esophagogastroduodenoscopy combined with colonoscopy. In the SG, the mean time of preoperative semaglutide interruption in patients with and without increased RGC was 10.5 ± 5.5 and 10.2 ± 5.6 days, respectively (p = 0.54). There was no relationship between semaglutide use and the amount/volume of RGC found on esophagogastroduodenoscopy (p = 0.99). Only one case (in the SG) of pulmonary aspiration was reported. CONCLUSIONS: Semaglutide was associated with increased RGC in patients undergoing elective esophagogastroduodenoscopy. Digestive symptoms prior to esophagogastroduodenoscopy were also predictive of increased RGC.
Subject(s)
Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/complications , Retrospective Studies , Endoscopy, Gastrointestinal/adverse effects , Colonoscopy , Anesthesia, General , Hypoglycemic Agents/adverse effectsABSTRACT
Introducción: La semaglutida es un fármaco que contribuye a la liberación de insulina por el páncreas y a la supresión del apetito por lo que lo convierte en un importante candidato para ser usado en el tratamiento de la diabesidad. Objetivo: Describir el efecto de la semaglutida en el tratamiento de las personas con diabesidad. Métodos: Se revisó la literatura publicada en el período comprendido de enero-febrero de 2021. Las palabras clave utilizadas fueron obesidad; diabetes mellitus; diabesidad; semaglutida; análogo del péptido similar al glucagón tipo 1. Se utilizaron como motores de búsqueda las bases de datos de Google Académico, PubMed y SciELO. Se evaluaron diferentes trabajos de revisión, investigación y páginas web que tenían menos de 10 años de publicados en idioma español, portugués o inglés, y que por el título trataban el tema de estudio. Fueron excluidos los artículos que no abordaron la relación entre diabetes y obesidad, así como el tratamiento con análogos del péptido similar al glucagón tipo 1. Esto permitió la consulta de 84 artículos, de los cuales 59 fueron referenciados. Conclusiones: El empleo de semaglutida favorece una mejor evolución en paciente con diabesidad, como complemento de una dieta y una actividad física adecuada. Al optimizar el control glucémico, contribuir a la pérdida de peso y a la mejoraría de ciertas comorbilidades, entre ellas la salud cardiovascular(AU)
Introduction: Semaglutide is a drug that contributes to the release of insulin from the pancreas and suppresses appetite, which makes it an important candidate for treating diabesity. Objective: To describe the role of semaglutide in the treatment of diabesity individuals. Methods: The necessary information to write this article was obtained in the 2022 two-month period January-February. The keywords used were obesity; Mellitus diabetes; diabesity; semaglutide; type 1 glucagon-like peptide analogue. The search engines corresponding to the Google Scholar, PubMed and SciElO databases were used. Different review, research and web pages were evaluated, which in general were published no more than 10 years ago, in Spanish, Portuguese or English and which dealt with the subject of study by title. Articles that did not address the relationship between diabetes and obesity, as well as treatment with glucagon-like peptide 1 analogues, were excluded. This allowed the consultation of 84 articles, 59 of them were referenced. Conclusions: The use of semaglutide, as a complement to a diet and physical activity appropriate to the needs of patients with diabesity, brought about several effects that favor better evolution of this health problem, by optimizing glycemic control, contributing to the loss of weight and the improvement of certain comorbidities, including cardiovascular health(AU)
Subject(s)
Humans , Male , Female , Diabetes Mellitus/epidemiology , Glucagon-Like Peptide-1 Receptor , Obesity/epidemiologyABSTRACT
ABSTRACT Pulmonary aspiration of gastric residues during anesthesia is a potentially fatal complication for which no specific treatment is available. The primary way to prevent its occurrence in the context of elective surgeries is adherence to fasting protocols. However, some clinical conditions can prolong the gastric emptying time, and the risk of aspiration may exist despite adequate fasting. Recognizing the risk factors for gastroparesis allows the adoption of preventive methods and is the primary way to reduce morbidity and mortality from pulmonary aspiration. In this scenario, the anesthesiologist can investigate the gastric content by using ultrasound, adjust the anesthetic technique, and even postpone elective surgeries. Here, we describe incidental computed tomography finding of solid contents in the stomach of a patient without prior identification of the risk factors for gastroparesis. The patient underwent elective renal nodule ablation under general anesthesia after fasting for 9 hours. During the procedure, solid contents in the stomach were noted on computed tomography. Subsequently, it was discovered that the patient had been using semaglutide for 6 days and had not disclosed this information. Semaglutide use may represent a new and significant risk factor for anesthesia-related pulmonary aspiration. Until studies provide information on the appropriate perioperative management of patients using semaglutide, anesthesiologists need to adopt preventive measures to avoid aspiration. Awareness of this potential association and open communication among patients, physicians, and anesthesia teams are essential for enhancing patient safety.
ABSTRACT
PURPOSE OF REVIEW: To discuss evidence supporting the use of glucagon-like peptide 1 receptor agonists (GLP-1RA) to treat obesity and their role as a cardioprotective drug. Obesity is not just a hypertrophy of the adipose tissue because it may become dysfunctional and inflamed resulting in increased insulin resistance. Being overweight is associated with increased incidence of cardiovascular events and weight loss achieved through lifestyle changes lowers risk factors, but has no clear effect on cardiovascular outcomes. In contrast, treating obesity with GLP-1RA decreases cardiovascular risk and the possible mechanisms of cardioprotection achieved by this class of drugs are discussed. GLP-1RA were initially developed to treat type 2 diabetes patients, in whom the effects upon glycemia and, moreover, weight loss, especially with long-acting GLP-1RA, were evident. However, cardiovascular safety trials in type 2 diabetes patients, the majority presenting cardiovascular disease and excess weight, showed that GLP-1 receptor agonists were indeed capable of decreasing cardiovascular risk. RECENT FINDINGS: Type 2 diabetes treatment with GLP-1RA liraglutide and semaglutide paved way to a ground-breaking therapy specific for obesity, as shown with the SCALE 3 mg/day liraglutide program and the STEP 2.4 mg/week semaglutide program. A novel molecule with superior performance is tirzepatide, a GLP-1 and GIP (Gastric Inhibitory Peptide) receptor agonist and recent results from the SURPASS and SURMOUNT programs are briefly described. Liraglutide was approved without a CVOT (Cardiovascular Outcome Trial) because authorities accepted the results from the LEADER study, designed for superiority. The SELECT study with semaglutide will report results only in 2023 and tirzepatide is being tested in patients with diabetes in the SURPASS-CVOT. Clinical studies highlight that GLP-1RA to treat obesity, alongside their concomitant cardioprotective effects, have become a hallmark in clinical science.
Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Cardiovascular Diseases/chemically induced , Cardiovascular Diseases/prevention & control , Clinical Trials as Topic , Diabetes Mellitus, Type 2/chemically induced , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide 1/therapeutic use , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptide-1 Receptor/therapeutic use , Humans , Hypoglycemic Agents/therapeutic use , Liraglutide/therapeutic use , Obesity/complications , Obesity/drug therapy , Weight LossABSTRACT
Cardiovascular events related to atherosclerosis are responsible for high morbidity and mortality among patients with type 2 diabetes. Improvement in care, especially in early stages, is crucial. Oral semaglutide, a glucagon-like peptide 1 analogue, controls blood glucose and results in significant body weight loss in patients with type 2 diabetes. Beyond these well-known effects, an interesting aspect of this drug is its antiatherogenic activity, which should be further explored in clinical practice. This paper reviews the evidence related to oral semaglutide decreasing cardiovascular risk in patients with type 2 diabetes, focusing on the drug's antiatherosclerotic properties. The glucagon-like peptide 1 analogue restores endothelial dysfunction, induces vasodilatation, and reduces plasma lipids. Oral semaglutide showed cardiovascular safety profile, with significant reduced risk of death from cardiovascular events. Based on current data, clinicians should consider oral semaglutide for type 2 diabetes management.
Subject(s)
Atherosclerosis/drug therapy , Blood Glucose/drug effects , Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptides/administration & dosage , Glycemic Control , Hypoglycemic Agents/administration & dosage , Incretins/administration & dosage , Administration, Oral , Animals , Atherosclerosis/diagnosis , Atherosclerosis/mortality , Biomarkers/blood , Blood Glucose/metabolism , Cause of Death , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/mortality , Glucagon-Like Peptides/adverse effects , Glycemic Control/adverse effects , Humans , Hypoglycemic Agents/adverse effects , Incretins/adverse effects , Risk Assessment , Risk Factors , Treatment OutcomeABSTRACT
BACKGROUND: There is currently a large arsenal of antidiabetic drugs available to treat type 2 diabetes (T2D). However, this is a serious chronic disease that affects millions of adults worldwide and is responsible for severe complications, comorbidities, and low quality of life when uncontrolled due mainly to delays in initiating treatment or inadequate therapy. This review article aims to clarify the therapeutic role of the oral formulation of the glucagon-like peptide 1 receptor agonist (GLP-1 RA) semaglutide in treating typical T2D patients. The discussion focused on metabolic, glycemic, and weight alteration effects and the safety of the therapy with this drug. MAIN TEXT: Therapy with glucagon-like peptide 1 receptor agonist (GLP-1 RA) promotes strategic changes in the pathophysiological pathway of T2D and improves the secretion of glucagon and insulin, which results in a reduction in blood glucose levels and the promotion of weight loss. Until recently, the only route for semaglutide administration was parenteral. However, an oral formulation of GLP-1 RA was recently developed and approved by the Brazilian Health Regulatory Agency (ANVISA) and the Food and Drug Administration (FDA) based on the Peptide Innovation for Early Diabetes Treatment (PIONEER) program results. A sequence of 10 clinical studies compared oral semaglutide with placebo or active standard-of-care medications (empagliflozin 25 mg, sitagliptin 100 mg, or liraglutide 1.8 mg) in different T2D populations. CONCLUSIONS: Oral semaglutide effectively reduces glycated hemoglobin (HbA1c) levels and body weight in a broad spectrum of patients with T2D and shows cardiovascular safety. Oral semaglutide broadens therapy options and facilitates the adoption of earlier GLP-1 RA treatment once T2D patients present low rates of treatment discontinuation. The main adverse events reported were related to the gastrointestinal tract, common to GLP-1 RA class drugs.