Agonist Usage Research Articles

The Impact of GLP-1 Agonist Therapy in Tibiotalar and Subtalar Fusion: A Propensity-Matched Analysis

Category: Diabetes; Ankle Introduction/Purpose: The rising prevalence of obesity and diabetes mellitus have rendered the usage of GLP-1 agonists increasingly commonplace since their introduction in 2005. Foot and ankle surgeons consistently provide orthopedic care to diabetic patients through tibiotalar and subtalar fusion. There is, however, a dearth of evidence to suggest whether outcomes of ankle fusion differ in patients treated with GLP-1 agonists. This study retrospectively compares rates of infection and failed fusion in patients who underwent tibiotalar or subtalar fusion with and without concurrent GLP-1 agonist therapy. Methods: The TriNetX Diamond Network was queried using CPT and ICD codes for patients with diabetes mellitus undergoing tibiotalar or subtalar fusions from 2005 to 2024. Diagnosis codes occurring within 1 year of the index procedure for: infection following a procedure (T81.4) and pseudoarthrosis after attempted fusion (M96.0) were compared using chi-squared statistical testing. Cohort balancing was performed categorically according to age at procedure, race, sex, and nicotine dependence. Cohort balancing was performed continuously for index BMI, Hemoglobin A1C, estimated Glomerular Filtration Rate (eGFR). Significance was set at p< 0.05 with associated 95% confidence intervals. Results: Overall, two propensity-matched cohorts of 708 patients were included in our analysis. Cohorts were not significantly different across any of the balancing parameters (p>.05). The postoperative infection rate was found to be significantly higher in the GLP-1-treated group (9.0%) than the non-treated group (5.6%) (p=0.02). No statistical significance was observed in the rate of postoperative pseudoarthrosis amongst patients who underwent fusion with (9.0%) and without (12.0%) GLP-1 agonist usage (p=0.08). Conclusion: Although GLP-1 agonists have provided significant benefit in the treatment of obesity and diabetes mellitus, results of this study suggest a previously unreported risk of postoperative infection associated with GLP-1 agonist use following ankle arthrodesis. Further investigation is needed GLP-1 agonists' effects on foot and ankle surgery. It is our hypothesis that previously demonstrated anti-inflammatory properties attenuate immune response and predispose patients to postoperative infection. Past inquiries have also demonstrated reduced osteoclast activity with GLP-1 agonist administration. Therefore, we suspect that decreased osteoclast activity at fusion margins may disrupt resorption of heat-necrosed bone, leaving a nidus for infection.

A meta-analysis of the incidence of acne vulgaris in patients treated with GLP-1 agonists.

With the emerging popularity of GLP-1 receptor agonists, patients are noticing acne vulgaris side effects that are seemingly related to the concurrent treatment with the drug. Due to the correspondence between these drugs' relatively recent emergence in the U.S. market and their high demand, it is important to investigate what is currently known in the literature so that patients can be properly informed. The aim of this study is to investigate the relationship, or lack thereof, between glucagon like peptide 1 (GLP-1) receptor agonist usage and acne-related side effects in patients. A web-based analysis of 6 GLP-1 receptor agonists (3 with a once-weekly dosing schedule, and 3 with a once-daily dosing schedule) was conducted on PubMed online database. Boolean criteria were used to narrow the search. Included in the meta-analysis were 45 research articles that fulfilled the search criteria. The results of the search showed that from the following long-acting GLP-1 receptor agonists, dulaglutide, exenatide extended release, and semaglutide (Wegovy), no conclusive acne side effects were reported. In addition, the results also showed that from the following short-acting GLP-1 receptor agonists, liraglutide, lixisenatide, and semaglutide (Rybelsus), no conclusive acne side effects were reported. Limitations of this study include a limited amount of literature regarding the relationship between GLP-1 agonists and acne vulgaris. It is unlikely that GLP-1 agonists themselves are directly responsible for the acne that some patients may develop during treatment. Rather, it is more probable that the weight loss yielded by treatment with these drugs may induce intrinsic physiologic and hormonal changes that induce or exacerbate acne vulgaris in such patients.

The Utilization of Glucagon-like Peptide 1 Agonists and Risk of Following External Eye Diseases in Type 2 Diabetes Mellitus Individuals: A Population-Based Study.

The glucagon-like peptide 1 (GLP-1) agonist showed anti-hyperglycemic and anti-inflammatory effects, which may retard the risk of external eye disease. The protective effect of GLP-1 agonist and dry eye disease (DED) was found, while the relationship between GLP-1 agonist and other corneal diseases was not clear. Herein, we aim to evaluate the association between the usage of GLP-1 agonists and the development of the following external eye disease in type 2 diabetes mellitus (T2DM) patients. A retrospective cohort study using the National Health Insurance Research Database (NHIRD) of Taiwan was conducted. The T2DM patients were divided into those with GLP-1 treatment and those without GLP-1 treatment and matched with a 1:2 ratio. The main outcomes were the development of dry eye disease (DED), superficial keratitis, and infectious keratitis. The Cox proportional hazard regression was adopted to produce the adjusted hazard ratio (aHR) with a 95% confidence interval (CI) of external eye diseases between groups. There were 115, 54, and 11 episodes of DED, superficial keratitis, and infectious keratitis in the GLP-1 group. Another 280, 168, and 31 events of DED, superficial keratitis, and infectious keratitis were recorded in the control group. The GLP-1 group demonstrated a significantly lower incidence of DED (aHR: 0.853, 95% CI: 0.668-0.989, p = 0.0356) and superficial keratitis (aHR: 0.670, 95% CI: 0.475-0.945, p = 0.0107) compared to the control group. In the subgroup analyses, the correlation of GLP-1 agonist and DED development was more prominent in patients younger than 60 years old (p = 0.0018). In conclusion, the GLP-1 agonist treatments are significantly associated with a lower incidence of subsequent DED and superficial keratitis, while the relationship was not significant between GLP-1 agonist usage and infectious keratitis.

Risk of delirium with antiepileptic drug use: a study based on the Japanese Adverse Drug Event Report database.

Antiepileptic drugs may cause delirium, and the risk may vary with each drug. However, related studies have provided inconsistent results. The aim of this study was to investigate whether the use of antiepileptic drugs is a risk factor for delirium development. Using the Japanese Adverse Drug Event Report database, we analysed 573,316 reports pertaining to the period from 2004 to 2020. Reporting odds ratios and 95% confidence intervals of delirium associated with use of antiepileptic drugs were calculated after adjusting for potential confounders. Furthermore, for each antiepileptic drug, we performed an analysis stratified based on older age and benzodiazepine receptor agonist usage. There were 27,439 reports of antiepileptic drug-related adverse events. Of these, 191 reports were associated with antiepileptic drugs and delirium (crude reporting odds ratio [cROR], 1.66; 95% confidence interval [CI], 1.43-1.93). The use of lacosamide (adjusted reporting odds ratio [aROR], 2.44; 95% CI, 1.24-4.80), lamotrigine (aROR, 1.54; 95% CI, 1.05-2.26), levetiracetam (aROR, 1.91; 95% CI, 1.35-2.71), and valproic acid (aROR, 1.49; 95% CI, 1.16-1.91) was related to a significantly higher reporting odds ratio for delirium, even after adjustment for possible confounding factors. However, when used in combination with benzodiazepine receptor agonists, none of the antiepileptic drugs were found to be associated with delirium. Our study's findings suggest that antiepileptic drug usage may be associated with delirium development.

Impact of COVID-19 pandemic on control of bronchial asthma in children attending the asthma clinic in a tertiary care centre in Kerala

Abstract BACKGROUND: COVID-19 pandemic led to widespread change in the life of people across the globe, including children, with far-reaching consequences. When control of disease is considered among children with asthma, a positive impact is to be expected. This study aimed to assess the impact of the COVID-19 pandemic on disease control among children with asthma. OBJECTIVES: The main objectives are (1) to compare the level of asthma control pre-COVID versus during the COVID pandemic in terms of exacerbations and short-acting beta agonist (SABA) usage and (2) to compare the use of inhaled corticosteroids (ICS) pre-COVID versus during the COVID pandemic. MATERIALS AND METHODS: Hospital-based study was conducted among children aged 5–15 years attending the asthma clinic of Government TD Medical College, Alappuzha, during the period May 2021–January 2022. Asthma control in terms of SABA usage, emergency visits, hospitalizations, and ICS usage was compared pre-COVID (before March 2020) to Complete lockdown (March 2020–May 2020), phased reopening (June 2020–May 2021) and after the lifting of major restrictions (June 2021–January 2022). Statistical analysis was done using IBM SPSS Statistics v.26. RESULTS: In total, 139 children were included in the study. A decrease was observed in the number of children requiring SABA as reliever therapy, with 18%, 25.9%, and 33.1% not requiring SABA during the complete lockdown, during phased reopening, and after the lifting of major restrictions, respectively, when compared to pre-COVID. A statistically significant decrease in hospitalizations and visits to the emergency department due to asthma exacerbations were also observed during various phases of the pandemic. ICS was stopped in 15.1%, 30.2%, and 35.3% of the study subjects during various phases of the pandemic without further exacerbations. CONCLUSION: There was a significant impact on asthma control during the pandemic, which was sustained during various phases of lifting restrictions.

Chemotherapy Dose Reductions and Dose Delays Due to Thrombocytopenia

Background: Chemotherapy-induced thrombocytopenia (CIT) is a challenging clinical scenario. A recent study of 15,521 patients showed that 13% of patients with solid tumors had thrombocytopenia within 3 months (Shaw, Eur J Haematol. 2021).Unfortunately, there are no guidelines for the management of CIT. Therefore, clinicians use strategies such dose reduction (DR) and/or dose delays (DD) to reduce the bleeding risk(Kuter, Haematologica. 2022). Although the incidence of CIT in various types of cancers and chemotherapeutic agents is known, studies showing an association between DR or DD and duration of CIT are lacking. It is known that DR and DD can increase mortality(Havrilesky, Crit Reviews in Onc/Hematology. 2015; Liutkauskiene, BMC Cancer. 2018). The association of cirrhosis and duration of thrombocytopenia in patients with CIT is also not well described. Therefore, we conducted a retrospective analysis to study the association between duration of thrombocytopenia and dose delays and reduction in patients with CIT. Methods: This study was approved by the Institutional Review Board. A retrospective analysis was performed using the electronic medical record (EMR) for adult patients who received chemotherapy for breast, GI, GU, and lung cancer from January 1st, 2016, to December 31st, 2020, at Rush University Cancer Center. Adult patients who developed thrombocytopenia during treatment (platelet count < 100 × 109 /L) were included in the study. Patients with thrombocytopenia preceding the initiation of chemotherapy were excluded. One hundred thirty-five patients met the study inclusion criteria. EMR were reviewed to collect data on DR and DD that had been clearly attributed to chemotherapy by the treating oncologist's documentation. Data for age at first thrombocytopenia (following treatment initiation), total duration of thrombocytopenia, presence of cirrhosis, and presence of liver metastasis was collected. Pearson's chi-square test and logistic regression were used to test the associations between duration of thrombocytopenia (grouped as <14 days or ≥ 14 days) and the proportion of patients who experienced at least one DR or DD. We similarly tested the association between thrombocytopenia duration and cirrhosis or liver metastasis. Results: First, we analyzed the association between DR, DD, and duration of thrombocytopenia. There was no statistically significant association between duration of thrombocytopenia and DR. However, we found that patients with DD had 4.1 times the odds of having increased duration of thrombocytopenia (≥ 14 days) compared to the patients without DD (OR = 4.1, 95% CI = 2.0 - 8.5, P-value = 0.0001). Then, we studied the association between DD and duration of thrombocytopenia in patients with cirrhosis or liver metastasis. We found that in this subset patients with DD had 3.9 times the odds of having thrombocytopenia duration ≥ 14 days compared to the patients without DD (OR = 3.9, 95% CI = 1.4 - 10.8, P-value = 0.008). We then looked at the association of having cirrhosis and liver metastasis on duration of thrombocytopenia. We found that there was no statistically significant association between presence of liver metastasis and duration of thrombocytopenia. However, patients with cirrhosis had 3.5 times the odds of having thrombocytopenia duration ≥14 days compared to patients without cirrhosis (OR = 3.5, 95% CI = 1.1 - 11.3, P-value = 0.03). Discussion: Our study shows that in patients with CIT, duration of thrombocytopenia impacts the risk of DD, especially in patients with either cirrhosis or liver metastasis. The finding of interest is that patients with cirrhosis have a 4-fold increased risk of developing longer duration of thrombocytopenia, which can lead to dose delays. This raises the question of whether patients with cirrhosis should be supported by thrombopoietin receptor agonists to treat the thrombocytopenia and prevent treatment delays. Thrombopoietin (TPO) receptor agonists such as Romiplostim are showing increasing promise in the treatment of CIT, and there are currently multiple active phase III trials underway with dose-reductions and dose-delays as clinical endpoints. Further research is needed to identify risk factors that can predict the development of CIT and to identify evidence-based platelet thresholds for TPO agonist usage in CIT patients.

GLP-1R polymorphism (rs1042044) and expression are associated with the risk of papillary thyroid cancer among the Egyptian population

Glucagon like peptide-1 receptor (GLP-1R) agonist usage has previously been linked to an elevated incidence of thyroid cell adenomas and carcinomas in animals. The goal of this study was to determine if there was an association between GLP-1R gene polymorphism and expression with the risk of papillary thyroid carcinoma (PTC) and its clinical characteristics among the Egyptian population. A total of eighty PTC patients and eighty healthy controls were included in the study. Real-time polymerase chain reaction (real-time PCR) and immunohistochemistry were used to determine GLP-1R expression in tumor tissue. The polymorphisms rs1042044 and rs6923761 in the GLP-1R gene were determined using PCR -restriction fragment length polymorphism (PCR-RFLP). PTC patients exhibited considerably greater frequencies of rs1042044 AA genotypes and A allele than controls (OR (95% CI)=4.5 (1.75-11.8), P<0.001; OR (95% CI)=2.032 (1.301-3.17), P<0.001 respectively). GLP-1R mRNA and protein expressions were higher in tumor samples than normal thyroid tissues among PTC patients. In addition, high GLP-1R expressions were more common in rs1042044 AA genotype carriers than CC carriers (P<0.001). GLP-1R mRNA expression showed 95 % sensitivity and 97% specificity for PTC diagnosis. Moreover, GLP-1R expression was closely associated with LN metastasis, tumor size, tumor stage, and multifocality in PTC patients. This research provides new evidence linking the GLP-1R genetic polymorphism and tissue expression to PTC risk and invasiveness among the Egyptian population.

Glucagon-Like Peptide1 Receptor Agonist Usage in Type2 Diabetes in Primary Care for the UK and Beyond: A Narrative Review.

The scientific landscape of treatments for type 2 diabetes (T2D) has changed rapidly in the last decade with newer treatments becoming available. However, a large proportion of people with T2D are not able to achieve glycaemic goals because of clinical inertia. The majority of T2D management is in primary care, where clinicians (medical, nursing and pharmacist staff) play an important role in addressing patient needs and achieving treatment goals. However, management of T2D is challenging because of the heterogeneity of T2D and complexity of comorbidity, time constraints, guidance overload and the evolving treatments. Additionally, the current coronavirus disease pandemic poses additional challenges to the management of chronic diseases such as T2D, including routine access to patients for monitoring and communication. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are a class of agents that have evolved rapidly in recent years. These agents act in a glucose-dependent manner to promote insulin secretion and inhibit glucagon secretion, as well as enhancing satiety and reducing hunger. As a result, they are effective treatment options for people with T2D, achieving glycated haemoglobin reductions, weight loss and potential cardiovascular benefit, as monotherapy or as add-on to other glucose-lowering therapies. However, given the complexity of managing T2D, it is important to equip primary care clinicians with clear information regarding efficacy, safety and appropriate positioning of GLP-1 RA therapies in clinical practice. This review provides a summary of clinical and real-world evidence along with practical guidance, with the aim of aiding primary care clinicians in the initiation and monitoring of GLP-1 RAs to help ensure that desired outcomes are realised. Furthermore, a benefit/risk tool has been developed on the basis of current available evidence and guidelines to support primary care clinicians in selecting individuals who are most likely to benefit from GLP-1 RA therapies, in addition to indicating clinical situations where caution is needed.

Immune Thrombocytopenia Secondary to COVID-19: a Systematic Review.

Immune thrombocytopenia, often known as immune thrombocytopenic purpura (ITP), has emerged as an important complication of COVID-19. A systematic review was done to analyze the clinical profile and outcomes in a total of 45 cases of new-onset ITP in COVID-19 patients described in literature until date. A comprehensive approach is essential for diagnosing COVID-19-associated ITP after excluding several concomitant factors that can cause thrombocytopenia in COVID-19. Majority of ITP cases (71%) were found to be elderly (> 50 years) and 75% cases had moderate-to-severe COVID-19. Three patients (7%) were in the pediatric age group. Reports of ITP in asymptomatic COVID-19 patients (7%) underscore the need for COVID-19 testing in newly diagnosed patients with ITP irrespective of COVID-19 symptoms amid this pandemic. ITP onset occurred in 20% cases 3 weeks after onset of COVID-19 symptoms, with many reports after clinical recovery. SARS-CoV-2-mediated immune thrombocytopenia can be attributed to the underlying immune dysregulation, susceptibility mutations in SOCS 1, and other mechanisms, including molecular mimicry, cryptic antigen expression, and epitope spreading. No bleeding manifestations were reported in 31% cases at diagnosis. Severe life-threatening bleeding was uncommon. One case of mortality was attributed to intracranial hemorrhage. Secondary Evans syndrome was diagnosed in one case. Good initial response to short course of glucocorticoids and intravenous immunoglobulin has been found with the exception of delayed lag response in one case. Thrombopoietin receptor agonist usage as a second-line agent has been noted in few cases for short duration with no adverse events. In the relatively short follow-up period, four relapses of ITP were found.

1596-P: Evaluating Reports of Pancreatic Malignancy and Liraglutide: A Pharmacovigilance Study of the FDA Adverse Event Reporting System

Background: Animal studies have raised concerns about glucagon-like peptide-1 (GLP-1) receptor agonist usage and incidence of pancreatic premalignant changes. Although randomized controlled Trials (RCTs) have not described this association, smaller size and shorter duration of RCTs may limit their statistical power to find such an association. Liraglutide utilization has been increasing due to the prescribing label change and indication for cardiovascular disease. Aim: Evaluate reporting associations between pancreatic cancer and liraglutide using FDA Adverse Event Reporting System (FAERS). Methods: FAERS reports from 1 January 2004 to 31 December 2018 were included in the study. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify pancreatic cancer cases. Reporting odds ratios (RORs) and corresponding 95% confidence intervals (CIs) for the reporting associations among liraglutide, metformin, glyburide, glipizide, and empagliflozin and pancreatic cancer were calculated. Results: A total of 10,015,622 reports were considered. Pancreatic cancer RORs (95% CI) in descending order were: Liraglutide 32.47 (30.53-34.52), metformin 6.85 (6.52-7.19), glyburide 5.24 (4.48-6.14), glipizide 3.83 (3.32-4.42), and empagliflozin 3.42 (2.50-4.67). The number of reports for pancreatic cancer increased from 2735 in 2010 to 4967 in 2018. Conclusion: Liraglutide had greater reporting associations when compared to other antidiabetes medications. Further studies are needed to determine if this signal is causal. Disclosure C.A. Alvarez: None. C. Teng: None. I. Mansi: None. Funding National Institutes of Health (K08DK101602)

Is gonadotropin-releasing hormone agonist usage really leading to thyroid dysfunction?

ObjectivesGonadotropin-releasing hormone agonist (GnRHa) could influence the levels of sex hormones and thyroid hormones. The aim of this study was to investigate the effect of GnRHa on thyroid function.Materials and methodsThe data of the patients were collected from the registrations of July 2014–October 2014. A total of 41 women who underwent one-time IVF cyclus were evaluated in this cross-sectional study. The patients were categorized into two groups according to the serum T3, T4, and TSH levels before and 2 weeks’ after the administration of GnRHa.ResultsMean basal TSH and mean TSH levels on hCG day were 1.98 ± 0.77 and 1.75 ± 0.70, respectively. The difference between the two groups was statistically significant (p < 0.05). GnRHa did not lead to statistically significant difference on serum-free T3 and T4 levels.ConclusionsIn conclusion, our results demonstrate that GnRHa led to a decrease on serum TSH level. Serum-free T3 and T4 levels were remained unchanged and this might be due to early measurement of the hormone levels (just 2 weeks later from GnRHa administration).

Nocturnal blood pressure changes in Parkinson's disease: correlation with autonomic dysfunction and vitamin D levels.

Nocturnal blood pressure (BP) changes are an indicator of autonomic dysfunction. We aim to investigate the correlation between nocturnal blood pressure (BP) variability, vitamin D levels and Parkinson's disease severity (PD) in this study. Thirty-five patients with PD participated in the study. Disease severity was evaluated by United Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr Scale (HYS). Equivalent levodopa dose was calculated and 25-hydroxyvitamin D levels were measured. The Non-Motor Symptom Questionnaire (NMSQ) was applied to all patients. Ambulatory BP monitoring for 24h was established. Patients were divided into three groups according to nocturnal BP results: dippers (normal finding-a decline in mean nighttime BP of more than 10%); non-dippers (pathological-a decline in mean nighttime BP of less than 10%); reverse dippers (pathological-an increase in mean nighttime BP) .The mean score of the NMSQ was higher in the group with HYS > 2 (p = 0.050). Four patients were dipper, 17 patients were non-dipper and 16 patients were reverse dipper. There was no significant difference between the three groups in terms of age, gender, disease duration, age of the disease onset, disease stage, disease duration, dopamine agonist usage, levodopa equivalent dose, vitamin D level and NMSQ scores. NMSQ scores are high in advanced PD. Ambulatory BP monitoring is useful in detecting autonomic dysfunction. The number of patients with non-dipping and reverse dipping is high in PD, independent from PD severity, drug dose, vitamin D and the other NMS symptoms.

Effects of inhaler therapy on mortality in patients with tuberculous destroyed lung and airflow limitation.

PurposeAlthough patients with tuberculous destroyed lung (TDL) receive long-acting muscarinic antagonist (LAMA) inhaler therapy, its effectiveness is not clear. This study evaluated the effect of LAMA inhaler therapy on mortality in patients with TDL and airflow limitation.Patients and methodsA retrospective cohort of 683 patients with TDL and airflow limitation was analyzed in this study. The mortality was compared between 177 patients treated with LAMA inhalers >360 days (LAMA group) and 506 patients not treated with LAMA inhalers or treated with LAMA inhalers for <360 days (non-LAMA group). Risk factors for mortality were analyzed with Cox proportional hazards models and survival analysis was performed after propensity score matching.ResultsPatients in the LAMA group appeared to have worse baseline characteristics, older mean age, lower lung function, higher X-ray severity, and were more likely to receive long-term oxygen therapy than those in the non-LAMA group. On multivariate analysis, LAMA inhaler usage was independently associated with lower risk of mortality (HR, 0.405; P=0.006) after adjusting age, gender, body mass index, smoking history, Charlson Comorbidity Index, lung function, X-ray severity, and long-term oxygen therapy. After propensity score matching to adjust for the above unbalanced baseline characteristics, patients in the LAMA group tended to have a better prognosis than those in the non-LAMA group (121 patients in each group, 5-year mortality rate: 2.5% vs 9.1%, P=0.057). If we performed the same analysis of propensity score matching even after excluding patients with corticosteroids/long-acting beta-2 agonist (ICS/LABA) usage, patients in the LAMA group had a better prognosis than those in the non-LAMA group (64 patients in each group, 5-year mortality rate: 3.1% vs 14.1%, P=0.039).ConclusionLAMA inhaler treatment might reduce mortality in patients with TDL and airflow limitation.

Utilization Patterns of Glucagon-Like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus in Italy: A Retrospective Cohort Study.

IntroductionReal-world evidence on glucagon-like peptide-1 receptor agonist (GLP-1 RAs) usage is emerging in different European countries but is lacking in Italy. This retrospective cohort study aimed to describe the real-world drug utilization patterns in patients initiating GLP-1 RAs for treating T2DM in Italy.MethodsAdults aged ≥ 20 years and with ≥ 1 oral antidiabetic drug (alone or in combination with insulin) other than GLP-1 RAs in the 6 months prior to initiating exenatide twice daily (exBID), exenatide once weekly (exQW), dulaglutide once weekly (DULA), liraglutide once daily (LIRA) or lixisenatide once daily (LIXI) between March and July 2016 were retrospectively identified in the Italian IMS LifeLink™ longitudinal prescriptions database (retail pharmacy data). Patients with ≥ 6-month follow-up (defined as evidence of any prescription activity) were included. Proportions of patients who remained persistent (continued treatment until discontinuation/switch) in the first 6 months and of those who discontinued or switched to a different GLP-1 RA over the entire follow-up were recorded. For each treatment, the average daily/weekly dosage (ADD/AWD) while persistent during the available follow-up was calculated.ResultsWe identified 7319 patients: 92 exBID, 970 exQW, 3368 DULA, 2573 LIRA and 316 LIXI. Across treatments, 89% patients were ≥ 50 years old, 54% were males, and the median follow-up duration ranged between 8.1 and 8.7 months. At 6 months, 35% exBID, 47% exQW, 62% DULA, 50% LIRA and 40% LIXI patients remained persistent. Over the entire follow-up, median persistence days varied from 73 (exBID) to > 300 days (DULA). The mean ± SD ADD/AWD was exBID: 17.7 ± 2.1 µg/day; exQW: 2.1 ± 0.1 mg/week; DULA: 1.5 ± 0.2 mg/week; LIRA: 1.5 ± 0.2 mg/day; LIXI: 21.0 ± 5.5 µg/day.ConclusionsThis real-world analysis suggests differences exist in persistence between patients treated with various GLP-1 RAs. Among the investigated treatments, patients prescribed exBID recorded the lowest and those prescribed DULA the highest persistence with therapy.FundingEli Lilly and Co., Indianapolis, IN, USA.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0396-2) contains supplementary material, which is available to authorized users.

The new NICE guidelines for type 2 diabetes – a critical analysis

“Common sense is not so common” – Voltaire (1694–1778) The latest NICE guidelines for the management of type 2 diabetes are now available for consultation. They contain sensible recommendations regarding lifestyle, patient education, monitoring and targets. Unfortunately, the pharmacotherapy section shows a distinct failure of common sense. The recommendations include using the insulin secretagogue repaglinide as a first-line agent, where metformin is not tolerated or contraindicated, or second-line in combination with metformin. Pioglitazone is recommended as the principal second-line therapy with metformin. The advice on glucagon-like peptide-1 receptor agonist (GLP-1ra) usage and assessment of efficacy and failure to recommend long acting analogue insulins over isophane are also major concerns. The recommendations appear to be based on meta- analyses and pharmacoeconomics, driven by an imperative on costs and failing to appreciate the “value” of the options under consideration. The cost to patients and the health service of the serious side-effects of these treatments is underestimated.Given the emphasis in these guidelines on the importance of lifestyle changes, including weight loss, plus an over-riding need to avoid hypoglycaemia, these pharmacotherapeutic recommendations appear paradoxical in the extreme.We believe that these recommendations, if enacted, will undermine seriously the reputation of NICE both nationally and internationally.

Long-acting muscarinic antagonist use in adults with asthma: real-life prescribing and outcomes of add-on therapy with tiotropium bromide.

BackgroundRandomized controlled trials indicate that addition of a long-acting muscarinic antagonist (LAMA) such as tiotropium may improve asthma control and reduce exacerbation risk in patients with poorly controlled asthma, but broader clinical studies are needed to investigate the effectiveness of LAMA in real-life asthma care.MethodsMedical records of adults with asthma (aged ≥18 years) prescribed tiotropium were obtained from the UK Optimum Patient Care Research Database for the period 2001–2013. Patients diagnosed with chronic obstructive pulmonary disease were excluded, but no other clinical exclusions were applied. Two primary outcomes were compared in the year before (baseline) and the year after (outcome) addition of tiotropium: exacerbations (asthma-related hospital emergency department attendance or inpatient admission, or acute oral corticosteroid course) and acute respiratory events (exacerbation or antibiotic prescription with lower respiratory consultation). Secondary outcomes included lung function test results and short-acting β2 agonist usage. The Wilcoxon signed-rank test was used for variables measured on the interval scale, the marginal homogeneity test for categorized variables, and the paired t-test for lung function indices.ResultsOf the 2,042 study patients, 83% were prescribed an inhaled corticosteroid and 68% a long-acting β2 agonist during the baseline year; 67% were prescribed both. Comparing baseline and outcome years, the percentage of patients having at least one exacerbation decreased from 37% to 27% (P<0.001) and the percentage having at least one acute respiratory event decreased from 58% to 47% (P<0.001). There were no significant changes in lung function, and usage of short-acting β2 agonists (in salbutamol/albuterol equivalents) increased from a median (interquartile range) of 274 (110, 548) to 329 (110, 603) μg/day (P=0.01).ConclusionIn this real-life asthma population, addition of LAMA therapy was associated with significant decreases in the incidence of exacerbations and antibiotic prescriptions for lower respiratory tract infections in the following year.

Addition of a 5-lipoxygenase-activating protein inhibitor to an inhaled corticosteroid (ICS) or an ICS/long-acting beta-2-agonist combination in subjects with asthma

Objective:To investigate the clinical benefits of ‘add-on’ therapy with GSK2190915 in combination with the inhaled corticosteroid (ICS) fluticasone propionate (FP) and the ICS/long-acting beta 2 agonist (LABA) combination FP/salmeterol in asthmatic subjects.Methods:Both studies were cross-over, randomized, double-blind, double-dummy and placebo-controlled in subjects with a forced expiratory volume in 1 second (FEV1) best of >50 and ≤80% of predicted. Add-on to ICS: Subjects (n = 162) aged ≥12 years received FP 100 µg twice daily (BID) plus GSK2190915 100 mg once daily (QD); GSK2190915 300 mg QD; montelukast 10 mg QD; salmeterol 50 µg BID or placebo. Add-on to ICS/LABA: Female subjects (n = 145) aged ≥18 years received FP/salmeterol 250/50 µg BID plus GSK2190915 300 mg QD, montelukast 10 mg QD or placebo. In both studies, the primary endpoint was trough FEV1 at the end of the treatment period. Secondary endpoints included a range of objective and patient-reported measures of efficacy.Results:Add-on to ICS: There was no statistically significant difference in the primary endpoint between either dose of GSK2190915 (add-on to FP) and placebo. Nominally statistically significant increases were demonstrated for GSK2190915 300 mg add-on relative to placebo for mean morning peak expiratory flow (p = 0.049), percentage of symptom-free days (p = 0.035) and percentage of symptom-free 24 h periods (p = 0.030). Add-on to ICS/LABA: There were no statistically significant differences on the primary endpoint between treatment regimens. Nominally statistically significant decreases were demonstrated in daytime (p = 0.023), night-time (p = 0.041) and 24 h (p = 0.019) short-acting beta 2 agonist usage with FP/salmeterol + GSK2190915 300 mg vs. FP/salmeterol + placebo.Conclusion:There was no clinically significant improvement in the primary endpoint following GSK2190915 add-on treatment; however, improvements in a range of secondary endpoints and biomarker data provided evidence of pharmacological activity. Improvements in response to background treatment may have been a limitation in both studies.Trial registration:Clinicaltrials.gov identifiers: NCT01156792 and NCT01248975.

Determine Efficacy of a Short Course of Montelukast in Children with Intermittent Asthma and Viral Infection

Introduction Mild intermittent asthma is common in children and viral infections are responsible for the majority of exacerbations. As leukotrienes are potent inflammatory mediators, some studies have shown that Montelukast, a leukotriene receptor antagonist, may be effective on reduction of asthma symptom. To determine whether a short course of Montelukast in asthmatic children with common cold would modify the severity of an asthma episode. Materials and Methods Children, aged 6-12 years with intermittent asthma participated in this randomized, double-blind, placebo-controlled clinical trial. Treatment with Montelukast or placebo was initiated at the onset of viral upper respiratory tract infection and continued for 7 days. Primary outcomes included the clinical manifestation: duration of episodes, daily symptom, nights symptoms and activity limitation. Secondary outcomes included the need for beta agonist usage, oral prednisolone, physician visit, hospital admission and school absence. Results A total of 187 children with intermittent asthma were randomized, 93 to Montelukast group and 94 to placebo group. Montelukast significantly decreased the cough by 17.3% (P<0.001), nighttime awakenings by 5.4% (P=0.01), interference with normal activity by 6% (P<0.01), time off from school by 6% (P<0.01), β-agonist usage by 17.2% (P<0.001) and doctor visits by12.2% (P<0.01) compared to placebo. Whereas there was a non significant reduction in wheezing, tachypnea, respiratory distress, asthma exacerbation, oral prednisolone and hospitalization (P=0.8). Conclusion A short course of Montelukast, introduced at the first sign of a viral infection, results in a reduction in cough, β-agonist use and nights awakened, time off from school and limitation of activity. More studies are needed to evaluate the optimal dose and duration of treatment.

Impact of laryngopharyngeal and gastroesophageal reflux on asthma control in children

A prospective study was carried out to determine the sensitivity and specificity of reflux symptoms and laryngeal findings to diagnose laryngopharyngeal reflux (LPR) and gastro-esophageal reflux (GER) in children with asthma by comparing the results of double probe pH monitorization and to determine the difference between controlled and uncontrolled asthma in terms of GER and LPR coexistence. A total of 50 patients (23 girls, mean age 10.8±0.4 years) with mild to moderate persistent asthma were included in this study. The patients were divided in two groups according to the asthma control status as controlled (n=27) vs. uncontrolled asthma (n=23). All patients completed the reflux symptom questionnaire and then they underwent flexible fiberoptic laryngoscopy and 24h double probe (pharyngeal and esophageal) pH monitorization. Laryngopharyngeal and gastroesophageal reflux were defined according to the double probe pH meter results. The prevalences of LPR and GER were 70% and 46% in asthmatic patients, respectively. The reflux symptom score and LPR disease index were not useful to predict LPR or GER. There was no association between asthma control status and LPR and GER. Vocal nodule seems to be a valuable sign to evaluate LPR in asthmatic children. The reflux symptom score and LPR disease index do not seem reliable to diagnose LPR and GER in children with asthma. The frequency of LPR and GER are independent of asthma control, atopy and long acting beta agonist usage.

Ionisers for chronic asthma.

Previous reports have shown that ion content in the air may have an effect on respiratory function. Results from studies which test the efficacy of air ionisers to reduce asthma symptoms are often inconclusive and their use as a treatment for asthma remains debatable. We conducted a systematic review of the available evidence to determine the effectiveness of positive and negative ion generators in people with asthma. We searched the Cochrane Airways Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) as well as the alternative medicine database AMED. Searches were current as of June 2012. Randomised controlled trials (parallel or crossover design studies) comparing ionisers with dummy ionisers (being negative or positive ion emitters), in children or adults with chronic asthma. Two reviewers independently assessed titles and abstracts of studies and assessed trial quality. Study quality was determined using two methods:The Cochrane approach to allocation concealment and the five point Jadad scale. Six studies were selected for inclusion (106 participants). No results were combined as the studies were all of a crossover design.EFFECTS OF NEGATIVE ION GENERATORS (five studies) No study reported a significant difference in lung function between ionised and control air (morning Peak expiratory flow (PEF) - three studies; forced expiratory flow in one second (FEV1) - one study). There were no significant differences in symptoms or beta-2 agonist usage between ionised and control air in three studies.EFFECTS OF POSITIVE ION GENERATORS (one study) This study demonstrated that although positively ionised air was associated with a larger fall in FEV1 with exercise, this did not reach statistical significance. Baseline FEV1 was not demonstrated to be significantly different between treatment groups. Based on the evidence currently available from randomised controlled trials, a recommendation cannot be given for the use of room air ionisers to reduce symptoms in patients with chronic asthma.