The effect of glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across baseline blood pressure categories: Analysis of the LEADER and SUSTAIN 6 trials.

It is unknown if the cardioprotective and renal effects of glucagon-like peptide-1 receptor agonists are consistent across blood pressure (BP) categories in patients with type 2 diabetes and at high risk of cardiovascular events. Using data from the LEADER (9340 patients) and SUSTAIN 6 (3297 patients) trials, we evaluated post hoc the cardiorenal effect of liraglutide and semaglutide on major adverse cardiovascular events (MACE) and nephropathy by baseline BP categories using a Cox proportional hazards model (treatment and subgroup as factors; adjusted for cardiorenal risk factors). Data from the two trials were analysed separately. In the LEADER and SUSTAIN 6 trials, the prevalence of stage 1 hypertension was 30% and 31%, respectively, and of stage 2 hypertension 41% and 43%, respectively. There was no statistical heterogeneity across the BP categories for the effects of liraglutide (P = .06 for MACE; P = .14 for nephropathy) or semaglutide (P = .40 for MACE; P = .27 for nephropathy) versus placebo. This implies that liraglutide and semaglutide may be beneficial for patients with type 2 diabetes, irrespective of their baseline BP.

Effects of glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across body mass index categories in type 2 diabetes: Results of the LEADER and SUSTAIN 6 trials.

Associations between body mass index (BMI) and the cardiovascular (CV) and kidney efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) are uncertain; therefore, data analysed separately from the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial and the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN 6) were examined. These international, randomized, placebo-controlled trials investigated liraglutide and semaglutide (both subcutaneous) in patients with T2D and at high risk of CV events. In post hoc analyses, patients were categorized by baseline BMI (<25, ≥25-<30, ≥30-<35 and ≥35 kg/m2 ), and CV and kidney outcomes with GLP-1 RA versus placebo were analysed. All baseline BMI data from LEADER (n = 9331) and SUSTAIN 6 (n = 3290) were included (91% and 92% of patients with overweight or obesity, respectively). In SUSTAIN 6, nominally significant heterogeneity of semaglutide efficacy by baseline BMI was observed for CV death/myocardial infarction/stroke (major adverse CV events, primary outcome of both; Pinteraction = .02); otherwise, there was no statistical heterogeneity for either GLP-1 RA versus placebo across BMI categories for key CV and kidney outcomes. The lack of statistical heterogeneity from these cardiorenal outcomes implies that liraglutide and semaglutide may be beneficial for many patients and is probable not to depend on their baseline BMI, but further study is needed.

Nutrition in primary and secondary prevention of cardiovascular risk in the continental and Mediterranean regions of Croatia.

BACKGROUND: The aim of this observational study was to evaluate the effect of Mediterranean and continental nutrition on cardiovascular risk in patients with acute and chronic coronary heart disease in Croatia. METHODS: The study included 1284 patients who were hospitalized in a 28-month period due to acute or chronic ischaemic heart disease in hospitals across Croatia. An individual questionnaire was prepared which enabled recording of various cardiovascular risk factors. RESULTS: Patients with chronic coronary artery disease have a better index of healthy diet than patients with acute coronary disease. Women have a better index of diet than men in both Croatian regions. When the prevalence of risk factors (impaired glucose tolerance, diabetes mellitus types I and II, hypercholesterolaemia, hypertriglyceridaemia and hypertension) in patients with Mediterranean and continental nutrition is compared, a trend is seen for patients who have risk factors to consume healthier food. CONCLUSION: The Mediterranean diet is associated with reduced risk of developing cardiovascular disease. This effect is more evident in patients with known cardiovascular disease.

Investigating the role of obstructive pulmonary diseases and eosinophil count at admission on all-cause mortality in SARS-CoV-2 patients : A single center registry-based retrospective cohort study.

INTRODUCTION: The impact of asthma and chronic obstructive pulmonary disease (COPD) in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV­2) infection is not clearly defined. Blood eosinophil count is a standard diagnostic test which, according to the previously published literature, might have a potential prognostic role on mortality in patients with SARS-CoV­2 infection. AIM: To investigate the potential prognostic value of peripheral blood eosinophil count on all-cause mortality of patients hospitalized with SARS-CoV­2 infection, as well as to assess the impact of asthma or COPD premorbidity on all-cause mortality. MATERIAL AND METHODS: We conducted a retrospective registry-based cohort study. Survival analysis was performed by employing the Cox proportional hazards regression model at 30 days of follow-up. Prognostic value of eosinophil count on all-cause mortality was assessed using receiver-operating characteristic (ROC) curve analysis. RESULTS: A total of 5653 participants were included in the study. Our model did not reveal that pre-existing asthma or COPD is a statistically significant covariate for all-cause mortality but, indicated that higher eosinophil count at admission might have a protective effect (hazard ratio, HR 0.13 (95% confidence interval, CI 0.06-0.27), p = 0.0001). ROC curve analysis indicates cut-off value of 20 cells/mm3 (81% specificity; 30.9% sensitivity). CONCLUSION: Our results indicate that eosinophil count at hospital admission might have a potential prognostic role for all-cause mortality at 30 days of follow-up; however this was not demonstrated for pre-existing obstructive lung diseases.

Safety of screening procedures with hand-held metal detectors among patients with implanted cardiac rhythm devices: a cross-sectional analysis.

BACKGROUND: Case reports suggest that the hand-held metal detectors used for security screening generate electromagnetic fields that may interfere with pacemaker and implantable cardioverter-defibrillator (ICD) function. OBJECTIVE: To assess changes in function of pacemakers and ICDs after exposure to hand-held metal detectors. DESIGN: Cross-sectional study. SETTING: Two medical centers in Europe. PATIENTS: 388 patients (209 with pacemakers and 179 with ICDs) presenting for routine follow-up of device function between September 2009 and December 2010. MEASUREMENTS: Abnormalities on electrocardiography suggestive of rhythm device malfunction (pacing inhibition, loss of capture, inappropriate mode switch, ventricular oversensing, and spontaneous reprogramming) after 30 seconds of exposure to 2 widely used hand-held metal detectors with a maximal electromagnetic flux density of 6.3 µT. RESULTS: No change in device function, including pacing or sensing abnormalities or device reprogramming, was observed in any patient. LIMITATIONS: The study included a convenience sample of patients, and the number of different device models tested was small. Testing was conducted in 2 clinic settings. CONCLUSION: Hand-held metal detectors did not affect the function of pacemakers or ICDs in this sample. The use of hand-held metal detectors for security screening is probably safe for patients with pacemakers and ICDs, but these findings require confirmation. PRIMARY FUNDING SOURCE: None.

Extensive asymptomatic pulmonary air embolism during CRT-implantation.

This report presents a case of pulmonary air embolism during implantation of a cardiac resynchronisation therapy system. For left ventricular pacing the thinnest available coronary sinus lead was used in association with a standard subclavian vein introducer sheath. It is hypothesised that the difference of size between the small lead diameter and the subclavian vein introducer sheath may have predisposed to air entry into the venous system.

The prevalence of overweight and obesity among Croatian hospitalized coronary heart disease patients.

The aim of this article was to investigate the prevalence of overweight and obesity using selected anthropometric variables in a sample of hospitalized coronary heart disease (CHD) patients in Croatia (N = 1,298). Prevalence of overweight and obesity in surveyed patient population was high: 48.2% of participants were overweight and 28.6% were obese according to their body mass index; measured through waist-to-hip ratio 54.5% of participants were centrally obese. These data on prevalences of overweight, obesity and central obesity show that although there are some reassuring trends, there is still considerable amount of work to be done if the prevalence of this cardiovascular risk factor is to be reduced further among Croatian CHD patients. While the prevalence of obesity seems to be on the decline, the prevalence of overweight is rising, which may be just an early warning sign of an incoming wave of obesity epidemic in future years.

The prevalence of hypertension among Croatian hospitalized coronary heart disease patients.

The aim of this article was to investigate the prevalence of hypertension with selected anthropometric variables in a sample of hospitalized coronary heart disease (CHD) patients in Croatia. This study investigated patients hospitalized in the period of October 1st 2007 until January 7th 2010 because of acute or chronic CHD in various hospitals in Croatia (N = 1,298). Prevalence of hypertension in surveyed patient population was high: 70.1% of participants had raised blood pressure (BP) or previously diagnosed hypertension. Men had statistically significantly higher mean diastolic BP values than women (78.91 +/- 8.97 vs. 77.12 +/- 10.61 mmHg, p = 0.011). Prevalence of hypertension was statistically significantly more frequent in women (80.6% vs. 65.8%, p < 0.001). Hypertension still represents an important problem among hospitalized Croatian CHD patients. Its prevalence, unfortunately, continues to increase in this population, suggesting that there is still great potential for improvement of preventive cardiology standards and measures that have already been undertaken.

The prevalence of diabetes mellitus and abnormal lipid status among Croatian hospitalized coronary heart disease patients.

The aim of this article was to investigate the prevalence of diabetes mellitus and abnormal lipid status with selected anthropometric variables in a sample of hospitalized coronary heart disease (CHD) patients in Croatia (N = 1,298). Prevalence of diabetes mellitus was 31.6% (statistically significantly more frequent in women, 35.7% vs. 30.0%), while prevalences of increased total cholesterol were 72.0%, decreased HDL-cholesterol 42.6% (statistically significantly more frequent in women, 50.2% vs. 39.6%), increased LDL-cholesterol 72.3% and increased triglycerides 51.5%. Reported data on prevalences of diabetes mellitus can be somewhat reassuring (a decrease in its prevalence compared to data from 2006, but they still signal a situation which is a lot worse than in 2002 and 2003); the trend of rising prevalences of dyslipidaemic cardiovascular risk factors must be a cause for an alarm, furthermore as today's preventive and treatment measures in cardiology, both primary and secondary, are strongly focused on dyslipidaemias.

The prevalence of smoking among Croatian hospitalized coronary heart disease patients.

The aim of this paper was to investigate the prevalence of smoking using selected anthropometric variables in a sample of hospitalized coronary heart disease (CHD) patients in Croatia (N = 1,298). A total of 444 subjects (34.6%) were non-smokers, 548 (42.6%) were smokers and 293 (22.8%) were ex-smokers. Men, on average, smoked more cigarettes per day than women (22.62 vs. 19.84 cigarettes, p < 0.001) and they also had bigger index "pack-years" than women (36.96 vs. 33.91, p = 0.024). Men were more often smokers and ex-smokers than women (47.4% vs. 30.8% for smokers and 25.0% vs. 22.8% for ex-smokers, p < 0.001). In this study a high prevalence of smoking was found among CHD patients in Croatia. Unless it is decreased, it can be expected that CHD patients in Croatia will continue to experience adverse effects more often than other CHD patients in the rest of Europe.

The CroHort study: cardiovascular behavioral risk factors in adults, school children and adolescents, hospitalized coronary heart disease patients, and cardio rehabilitation groups in Croatia.

Based on repeated measurement of health behaviors the CroHort Study showed that health behavior explains a great deal more of class inequalities in mortality than observed in previous studies. These include decreasing prevalence of smoking and increase in obesity, hypertension and diabetes mellitus. The lowest prevalence of health risks was recorded among children and adolescents, followed by general adult population from the CroHort Study. Hospitalized coronary heart disease patients had higher risks prevalence than general population, while the highest prevalence of risks was recorded among patients in cardiac rehabilitation program. The higher levels of stress were associated to lower financial conditions, poorer social functioning and poorer mental health for both men and women. Higher levels of stress were also associated with heart problems, higher alcohol consumption in men while in women stress was associated to poorer general health, higher age and lower levels of education.

Association of chronic inflammation with cardiovascular risk in chronic obstructive pulmonary disease-A cross-sectional study.

Background and Aims: COPD is progressive lung disease with known higher cardiovascular (CV) risk, mainly attributed to smoking of cigarettes as the main etiological factor of disease. The aim of this study was to compare CV risk in patients with COPD to control groups of smokers and non-COPD and to investigate the relation of lung function variables, COPD severity, and smoking with Systemic Coronary Risk Estimation (SCORE) risk calculation, arterial stiffness (AS) values, and biological systemic inflammatory markers. Methods: A total of 208 subjects were included in this study: 61 subjects diagnosed with COPD, 83 smokers without COPD, and 64 nonsmokers without COPD. Medical history and clinical data were recorded, including assessment of pulmonary function and AS, calculation of ankle-brachial index, blood analysis, and CV risk assessment by SCORE risk calculation. Results: Subjects with COPD had significantly higher values of SCORE calculation of risk, central aortic pressure, AS, and markers of systemic inflammation compared to control groups of smokers and nonsmokers without COPD (p < 0.001). Furthermore, statistically significant increase in hs-CRP concentration was found between the COPD group and the control group of non-COPD smokers (p < 0.001), and a statistically significantly higher SCORE calculation was found in the COPD group compared to control groups of smokers and nonsmokers without COPD (p < 0.001). Conclusion: The results of the research support further identification and research of biological markers and simple specific tests such as arteriography that will enable progress in personalized treatment of patients with COPD and better primary and secondary prevention of comorbidities with the aim of improved treatment outcome.

[European guidelines on the diagnosis and management of pulmonary embolism]. / Smjernice Europskoga kardioloskog drustva za dijagnosticiranje i lijecenje plucne embolije.

We report on the 2008 update of Guidelines on the diagnosis and management of acute pulmonary embolism (PE) of the European Society of Cardiology that have been endorsed and recommended by the Croatian Cardiac Society. The guidelines focus on currently available and validated methods of diagnosis, prognostic assessment (prediction of outcome and death risk), treatment of pulmonary embolism and management in specific settings including pregnancy, malignancy, non-thrombotic PE, right heart thrombi, heparin-induced thrombocytopenia, chronic thromboembolic pulmonary hypertension. The novelty of these guidelines is the stratification of PE into high-risk, low-risk and intermediate-risk of PE-related early death, which has important consequences for treatment, rather than the use of misleading terms such as zmassive', zsubmassive' and znon-massive' pulmonary embolism. The anticoagulants remain the mainstay of therapy, with thrombolytic therapy being an therapeutic option in patients with high-risk PE presenting with cardiogenic shock and/or persistent arterial hypotension.

[Features and pathophysiology of acute coronary syndrome]. / Oblici i patofiziologija akutnog koronarnog sindroma.

Coronary heart disease (CHD) is the leading cause of death in developed countries, and it also has fastest growing death rates in developing countries. Patients with acute coronary syndromes (ACS) are divided into two groups - those with and those without ST segment elevation. ACS without ST segment elevation also includes unstable angina pectoris (UA) any non-ST elevation myocardial infarction (NSTEMI). It is important to note that UA is defined as ischemic chest pain at rest without a rise in serum cardiac biomarkers, while the establishment of NSTEMI diagnosis requires a rise in serum cardiac biomarkers. ACS with ST segment elevation is STEMI, and it includes both ST segment elevation and a rise in serum cardiac biomarkers. Connection of UA, NSTEMI and STEMI is based on the fact that these are closely connected conditions with similar pathogenesis and clinical presentation, but they do differ by the level of severity. The main difference lies in the fact whether or not the ischemia is serious enough to cause myocardial damage of such an extent that will cause the release of a sufficient amount of serum cardiac biomarkers so that these can be discovered and measured in serum (for example, cardiac troponin). The key role in ACS is played by atherosclerosis, atherosclerotic plaque and plaque rupture, in combination with thrombosis as an event of paramount importance--thrombosis.

[The role of diagnostic work-up at university hospital emergency service and coronary care unit in the management of acute coronary syndrome patients]. / Znacenje dijagnostickih postupaka u hitnoj sluzbi i koronarnoj jedinici klinicke bolnice u zbrinjavanju bolesnika s akutnim koronarnim sindromom.

Acute coronary syndrome (ACS) represents a significant global socioeconomic problem. In the United States, 6-7 million patients present to emergency service annually for chest pain or symptoms of ACS, the diagnosis of ACS being confirmed in 20-25% of these patients.There are two groups of ACS patients, with chest pain as the main and common the presentation that basically has the same pathophysiologic substrate. The groups show differences in electrocardiogram (ECG) changes, or in the presence or absence of ST elevation that distinguishes acute coronary syndrome with ST elevation, or acute myocardial infarction with ST elevation from acute coronary syndrome without ST elevation (ACS-NSTE). Within these groups there are subgroups of patients with acute myocardial infarction without ST elevation (NSTEMI) and patients with unstable angina pectoris (UA). Subgroup distinction between UA and NSTEMI is based on the findings of elevated cardiac markers (troponin). Diagnostic procedures performed at emergency service and coronary unit include history and clinical status, ECG, laboratory testing for cardiac markers and other biochemical parameters, heart and lung x-ray, heart ultrasound, radionuclide methods, and assessment of the risk level (risk score). It should be noted that history data, ECG findings and testing for cardiac markers are of particular importance in setting the diagnosis of ACS. Other useful methods of risk assessment include TIMI degree of risk, which is in general use because of its simplicity, but is less predictive, and the Pursuit and Frisco degree of risk. Regardless of the method used, it is recommended to determine the degree of risk for every patient on admission and at discharge.

[Anti-ischemic therapy in patients with STEMI or NSTEMI treated at county and university hospitals]. / Antiishemijska terapija bolesnika sa STEMI ili NSTEMI u zupanijskoj i klinickoj bolnici.

The objective of prehospital care of patients with acute coronary syndrom (ACS) [acute ST segment elevation myocardial infarction (STEMI), acute non-ST segment elevation myocardial infarction (NSTEMI), and unstable angina (UA)], is prompt diagnosis of the acute myocardial infarction, patient's risk assessment, drug administration in order to reduce patient's pain and fear, and prevention or treatment of heart failure. In hospital treatment therapeutic procedures include reperfusion therapy, limitation of infarction zone, treatment of complications (heart failure, life-threatening arrhythmias), prevention of reinfarction, heart failure and eventually prevention of sudden cardiac death. Acute therapeutic procedures include revascularization, anti-ischemic and antithrombolytic treatment, possible surgical revascularization and treatment of complications (arrhythmias, heart failure). The patients with STEMI that present within 3-12 hours from the onset of chest pain should undergo primary percutaneous coronary intervention (PCI). In case of presentation within 3 hours from the occurrence of chest pain, the administration of thrombolytic therapy in this period is equally efficient as PCI. Regardless of reperfusion regimen, the anti-ischemics administered including nitrates (nitroglycerin); intravenous analgesics (morphine-sulfate); O2 2-4 L/min; beta-adrenergic blockers; calcium channel blockers; angiotensin converting enzyme inhibitors (ACE-I); magnesium and glucose-insulin-potassium have proved to be efficient as shown by study results and clinical experience. The mechanism of action of anti-ischemics includes reduction in myocardial oxygen consumption achieved by a decrease of heart frequency, reduction of systemic blood pressure and reduction in myocardial contractility by vasodilatation and consequent better myocardial oxygen supply. The outstanding results of major clinical studies are presented, and main guidelines for anti-ischemic therapy of ACS adopted by the international professional associations are set forth.

Comparative efficacy of once-weekly semaglutide versus SGLT-2 inhibitors in patients inadequately controlled with one to two oral antidiabetic drugs: a systematic literature review and network meta-analysis.

OBJECTIVE: To determine the comparative efficacy of once-weekly semaglutide relative to sodium-glucose cotransporter 2 inhibitors (SGLT-2is) licensed in Europe and North America among patients with type 2 diabetes (T2D) inadequately controlled with 1-2 oral antidiabetics (OADs), using a network meta-analysis (NMA). Design systematic review and network meta-analysis. Data Sources EMBASE, MEDLINE and CENTRAL were searched from January 1994 to August 2017. METHODS: Randomised controlled trials with ≥20 weeks of treatment evaluating once-weekly semaglutide or SGLT-2is. Primary outcomes included change from baseline in: HbA1c, weight, systolic blood pressure, postprandial blood glucose and fasting plasma glucose. Fixed-effect and random-effect Bayesian NMA were used to indirectly compare treatment effects at 26 (±4) weeks. Metaregression and sensitivity analyses were conducted. Model selection was performed using the deviance information criterion and consistency was assessed by comparing indirect (edge-splitting) to direct evidence. RESULTS: Forty-eight publications representing 21 trials were included. The mean differences (MD) in change from baseline in HbA1c of once-weekly semaglutide 1.0 mg versus SGLT-2is ranged from -0.56% for canagliflozin 300 mg (95% credible interval (CrI): -0.76 to -0.33%), to -0.95% for dapagliflozin 5 mg (95% CrI: -1.20 to -0.69%). The MD in change from baseline in weight of once-weekly semaglutide 1.0 mg versus SGLT-2is ranged from -1.35 kg for canagliflozin 300 mg to -2.48 kg for dapagliflozin 5 mg, while change from baseline in fasting plasma glucose ranged from -0.41 mmol/L for canagliflozin 300 mg to -1.37 mmol/L for dapagliflozin 5 mg. Once-weekly semaglutide was not statistically differentiable than all SGLT-2is in reducing systolic blood pressure. NMA was not feasible for postprandial blood glucose and safety outcomes. CONCLUSION: Once-weekly semaglutide demonstrated statistically significant and clinically meaningful reductions in HbA1c and body weight in T2D patients inadequately controlled with 1-2 OADs compared to all SGLT-2is licensed in Europe and North America.

The utilization of antibiotics in the management of acute pancreatitis--experience from one transitional country university hospital.

The aim of the study was to analyze the evidence-based use of antibiotic therapy in the treatment of acute pancreatitis and to identify factors influencing the introduction of antibiotic therapy in the setting of transitional country clinical hospital. This retrospective study was conducted at Department of Internal Medicine at University Hospital Dubrava in Zagreb, Croatia. Data were collected from hospital records of patients treated for acute pancreatitis from January 1st, 2005 till December 31st, 2005. Data collected from patients' histories were compared with indications for antibiotic treatment and antibiotics with demonstrated therapeutic efficacy in acute pancreatitis which were obtained from published literature. Logistic regression was used to identify factors with a significant impact on deciding on the introduction of antibiotic therapy, and multivariate analysis was used to identify factors with a significant impact on the cost of treatment. Statistical significance was set at p < 0.05. Antibiotic therapy was used in 67.7% of patients with acute pancreatitis. Combination of amoxicillin plus clavulanic acid was most frequently administered, either as monotherapy or in combination with metronidazole and/or gentamicin (37.3%), followed by cefuroxime (32.8%) and cefoperazone (26.9%). The choice of antibiotic was appropriate in 35.8% of study patients; however in 29.9% of patients who were administered antibiotics had no indication for this therapy; and 46.9% of patients who had indications for receiving antibiotic therapy didn't receive it. In the groups of patients treated with antibiotics, the cost of treatment was significantly higher compared to groups of patients who were not treated with antibiotics (p = 0.0035; p = 0.0026). In addition to antibiotic therapy, the cost of treatment was significantly influenced by the length of hospital stay and treatment at intensive care unit. The use of antibiotics in the setting of transitional country university hospital in patients with acute pancreatitis is not evidence-based. Decision on the introduction of antibiotic therapy is not based on objective parameters of disease severity or evidence of therapeutic efficacy of particular antibiotics. The cost of treatment is significantly increased by the use of antibiotic therapy.

A Systematic Literature Review and Network Meta-Analysis Comparing Once-Weekly Semaglutide with Other GLP-1 Receptor Agonists in Patients with Type 2 Diabetes Previously Receiving 1-2 Oral Anti-Diabetic Drugs.

INTRODUCTION: Once-weekly semaglutide is a new glucagon-like peptide-1 (GLP-1) analogue administered at a 1.0 or 0.5 mg dose. As head-to-head trials assessing once-weekly semaglutide as an add-on to 1-2 oral anti-diabetic drugs (OADs) vs other GLP-1 receptor agonists (GLP-1 RAs) are limited, a network meta-analysis (NMA) was performed. The objective was to assess the relative efficacy and safety of once-weekly semaglutide vs GLP-1 RAs in patients with type 2 diabetes (T2D) inadequately controlled on 1-2 OADs. METHODS: A systematic literature review (SLR) was conducted in order to identify trials of GLP-1 RAs in patients inadequately controlled on 1-2 OADs. Data at 24 ± 4 weeks were extracted for efficacy and safety outcomes (feasible for analysis in a NMA), which included the key outcomes of change from baseline in glycated hemoglobin (HbA1c), systolic blood pressure (SBP), and weight, as well as discontinuation due to adverse events (AEs). Data were synthesized using a NMA and a Bayesian framework. RESULTS: In total, 26 studies were included across the base case analyses. Once-weekly semaglutide 1.0 mg was associated with significantly greater reductions in HbA1c and weight vs all GLP-1 RA comparators. Once-weekly semaglutide 0.5 mg also achieved significantly greater reductions in HbA1c and weight compared with the majority of other GLP-1 RAs. Both doses of once-weekly semaglutide were associated with similar odds of discontinuation due to AEs compared with other GLP-1 RAs. CONCLUSION: Overall, once-weekly semaglutide 1.0 mg as an add-on to 1-2 OADs is the most efficacious GLP-1 RA in terms of the reduction of HbA1c and weight from baseline after 6 months of treatment. In addition, the analysis suggests that once-weekly semaglutide is well tolerated and not associated with an increase in discontinuations due to AEs compared with other GLP-1 RAs. FUNDING: Novo Nordisk.

A Systematic Literature Review and Network Meta-Analysis Comparing Once-Weekly Semaglutide with Other GLP-1 Receptor Agonists in Patients with Type 2 Diabetes Previously Receiving Basal Insulin.

INTRODUCTION: Once-weekly semaglutide is a glucagon-like peptide-1 (GLP-1) analogue that is currently available as 1.0 mg and 0.5 mg dose for the treatment of type 2 diabetes (T2D). Currently, no head-to-head trial investigating once-weekly semaglutide as an add-on to basal insulin vs other GLP-1 receptor agonists (GLP-1 RAs) is available. The aim of this study was to conduct a network meta-analysis (NMA) to assess the efficacy and safety of once-weekly semaglutide vs other GLP-1 RAs in patients with T2D inadequately controlled on basal insulin. METHODS: A systematic literature review was performed to identify all trials of GLP-1 RAs as an add-on to basal insulin in patients with T2D. Data at 24 ± 4 weeks were extracted for efficacy and safety outcomes (feasible for analysis in an NMA), including the change from baseline in glycated hemoglobin (HbA1c), body weight, and systolic blood pressure, and the incidence of nausea, vomiting, and diarrhea. Data were synthesized using a NMA and a Bayesian framework. RESULTS: In total, eight studies were included across the base-case analyses. The results demonstrate that once-weekly semaglutide 1.0 mg was associated with significantly greater reductions in HbA1c (- 0.88% to - 1.39% vs comparators) and weight (- 1.49 to - 4.69 kg vs comparators) and similar odds of experiencing nausea, vomiting, or diarrhea vs all GLP-1 RA comparators. Once-weekly semaglutide 1.0 mg was also equally effective at reducing systolic blood pressure compared with liraglutide 1.8 mg. Once-weekly semaglutide 0.5 mg significantly reduced HbA1c vs the majority of other GLP-1 RAs, except liraglutide 1.8 mg QD. The odds of experiencing nausea were significantly lower with once-weekly semaglutide 0.5 mg compared with all GLP-1 RA comparators. CONCLUSION: Once-weekly semaglutide 1.0 mg as an add-on to basal insulin is likely to be the most efficacious GLP-1 RA for reducing HbA1c and weight from baseline after 6 months of treatment. The efficacy of once-weekly semaglutide is not associated with a significant increase in the incidence of gastrointestinal side-effects vs other GLP-1 RAs. FUNDING: Novo Nordisk.