Estimated Life-Years Gained Free of New or Recurrent Major Cardiovascular Events With the Addition of Semaglutide to Standard of Care in People With Type 2 Diabetes and High Cardiovascular Risk.

OBJECTIVE: Semaglutide, a glucagon-like peptide 1 receptor agonist, reduced major adverse cardiovascular events (MACE) in people with type 2 diabetes (T2D) at high risk of cardiovascular disease (CVD) in a post hoc analysis of pooled data from Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN) 6 and Peptide Innovation for Early Diabetes Treatment (PIONEER) 6. We estimated the benefit of adding semaglutide to standard of care (SoC) on life-years free of new/recurrent CVD events in people with T2D at high risk of CVD. RESEARCH DESIGN AND METHODS: The Diabetes Lifetime-perspective prediction (DIAL) competing risk-adjusted lifetime CVD risk model for people with T2D was developed previously. Baseline characteristics of the pooled cohort from SUSTAIN 6 and PIONEER 6 (POOLED cohort) (N = 6,480) were used to estimate individual life expectancy free of CVD for patients in the POOLED cohort. The hazard ratio of MACE from adding semaglutide to SoC was derived from the POOLED cohort (hazard ratio [HR] 0.76 [95% CI 0.62-0.92]) and combined with an individual's risk to estimate their CVD benefit. RESULTS: Adding semaglutide to SoC was associated with a wide distribution in life-years free of CVD gained, with a mean increase of 1.7 (95% CI 0.5-2.9) life-years. Estimated life-years free of CVD gained with semaglutide was dependent on baseline risk (life-years free of CVD gained in individuals with established CVD vs. those with cardiovascular risk factors only: 2.0 vs. 0.2) and age at treatment initiation. CONCLUSIONS: Adding semaglutide to SoC was associated with a gain in life-years free of CVD events that was dependent on baseline CVD risk and age at treatment initiation. This study helps contextualize the results of semaglutide clinical trials.

Once-Daily Oral Semaglutide Versus Injectable GLP-1 RAs in People with Type 2 Diabetes Inadequately Controlled on Basal Insulin: Systematic Review and Network Meta-analysis.

INTRODUCTION: The relative efficacy and safety of once-daily oral semaglutide vs. injectable glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in subjects with type 2 diabetes (T2D) inadequately controlled on basal insulin were assessed using network meta-analysis (NMA). METHODS: A systematic literature review (SLR) was performed to identify randomised controlled trials of GLP-1 RAs in this population. Data at 26 ± 4 weeks were extracted for efficacy and safety outcomes feasible for the NMA: change from baseline in glycated haemoglobin (HbA1c), weight and blood pressure; HbA1c target levels (< 7.0% and ≤ 6.5%); composite endpoint; incidence of nausea, vomiting or diarrhoea. Comparators of interest were all licensed doses of dulaglutide, exenatide, liraglutide, lixisenatide and once-weekly injectable semaglutide. RESULTS: The NMA included seven trials. Once-daily oral semaglutide 14 mg was associated with significantly greater HbA1c reductions vs. most comparators (treatment differences: - 0.42 to - 1.32%); differences vs. once-weekly injectable semaglutide (0.5 mg and 1 mg doses) were not statistically significant. Once-daily oral semaglutide 14 mg was associated with significantly greater weight reductions vs. exenatide 2 mg and lixisenatide 20 µg (- 2.21 and - 2.39 kg respectively); non-statistically significant weight reductions in favour of once-daily oral semaglutide 14 mg were observed vs. all other comparators except once-weekly injectable semaglutide 1 mg. Similar trends were observed for the proportion of subjects achieving HbA1c < 7.0% and ≤ 6.5% and the composite endpoint. Once-daily oral semaglutide 14 mg was associated with similar odds of experiencing nausea, vomiting or diarrhoea vs. all comparators. CONCLUSION: Once-daily oral semaglutide 14 mg, as an add-on to basal insulin, is an efficacious treatment for reducing HbA1c and weight and meeting glycaemic targets at 26 ± 4 weeks. Once-daily oral semaglutide 14 mg also offers the option of an oral treatment with similar or better efficacy and similar tolerability vs. most injectable GLP-1 RAs.

Oral Semaglutide Versus Empagliflozin, Sitagliptin and Liraglutide in the UK: Long-Term Cost-Effectiveness Analyses Based on the PIONEER Clinical Trial Programme.

INTRODUCTION: The PIONEER trial programme showed that, after 52 weeks, the novel oral glucagon-like peptide-1 (GLP-1) analogue semaglutide 14 mg was associated with significantly greater reductions in glycated haemoglobin (HbA1c) versus a sodium-glucose cotransporter-2 inhibitor (empagliflozin 25 mg), a dipeptidyl peptidase-4 inhibitor (sitagliptin 100 mg) and an injectable GLP-1 analogue (liraglutide 1.8 mg). The aim of the present analysis was to assess the long-term cost-effectiveness of oral semaglutide 14 mg versus each of these comparators in the UK setting. METHODS: Analyses were performed from a healthcare payer perspective using the IQVIA CORE Diabetes Model, in which outcomes were projected over patient lifetimes (50 years). Baseline cohort characteristics and treatment effects were based on 52-week data from the PIONEER 2, 3 and 4 randomised controlled trials, comparing oral semaglutide with empagliflozin, sitagliptin and liraglutide, respectively. Treatment switching occurred when HbA1c exceeded 7.5% (58 mmol/mol). Utilities, treatment costs and costs of diabetes-related complications (in pounds sterling [GBP]) were taken from published sources. The acquisition cost of oral semaglutide was assumed to match that of once-weekly semaglutide. RESULTS: Oral semaglutide was associated with improvements in quality-adjusted life expectancy of 0.09 quality-adjusted life years (QALYs) versus empagliflozin, 0.20 QALYs versus sitagliptin and 0.07 QALYs versus liraglutide. Direct costs over a patient's lifetime were GBP 971 and GBP 963 higher with oral semaglutide than with empagliflozin and sitagliptin, respectively, but GBP 1551 lower versus liraglutide. Oral semaglutide was associated with a reduced incidence of diabetes-related complications versus all comparators. Therefore, oral semaglutide 14 mg was associated with incremental cost-effectiveness ratios of GBP 11,006 and 4930 per QALY gained versus empagliflozin 25 mg and sitagliptin 100 mg, respectively, and was more effective and less costly (dominant) versus liraglutide 1.8 mg. CONCLUSION: Oral semaglutide was cost-effective versus empagliflozin and sitagliptin, and dominant versus liraglutide, for the treatment of type 2 diabetes in the UK.

Orally Administered Semaglutide Versus GLP-1 RAs in Patients with Type 2 Diabetes Previously Receiving 1-2 Oral Antidiabetics: Systematic Review and Network Meta-Analysis.

INTRODUCTION: Orally administered semaglutide is the first glucagon-like peptide 1 receptor agonist (GLP-1 RA) for oral administration. As head-to-head trials assessing orally administered semaglutide as an add-on to 1-2 oral antidiabetic drugs (OADs) vs other GLP-1 RAs are limited, a network meta-analysis (NMA) was performed to assess the relative efficacy and safety of orally administered semaglutide 14 mg once-daily (QD) vs injectable GLP-1 RAs in patients with type 2 diabetes inadequately controlled on 1-2 OADs. METHODS: A systematic literature review was conducted to identify randomised controlled trials of GLP-1 RAs in patients inadequately controlled on 1-2 OADs. Data at 26 ± 4 weeks were extracted for efficacy and safety outcomes feasible for the NMA: change from baseline in glycated haemoglobin (HbA1c), weight, HbA1c target levels (< 7.0% and ≤ 6.5%), blood pressure, and any gastrointestinal adverse events specified in system organ class. Data were synthesised using NMA and a Bayesian framework. RESULTS: In total, 27 studies were included in the analyses. Orally administered semaglutide 14 mg QD was associated with significantly greater reductions in HbA1c vs most comparators, and numerically greater reductions vs semaglutide 0.5 mg once-weekly (QW), dulaglutide 1.5 mg QW and liraglutide 1.8 mg QD. HbA1c reductions with semaglutide 1 mg QW were numerically greater than those with orally administered semaglutide 14 mg QD. Reductions in body weight for orally administered semaglutide 14 mg QD were significantly greater than all comparators except semaglutide QW (both doses). Orally administered semaglutide QD 14 mg was associated with statistically similar odds of experiencing gastrointestinal adverse events vs injectable GLP-1 RAs. CONCLUSION: Orally administered semaglutide 14 mg QD as an add-on to 1-2 OADs is one of the most efficacious GLP-1 RAs for reducing HbA1c and body weight at 26 ± 4 weeks. Orally administered semaglutide 14 mg QD is well tolerated, with a safety profile in line with the GLP-1 RA class. FUNDING: Novo Nordisk.

Economic evaluation of paliperidone palmitate once monthly for treating chronic schizophrenia patients in the United Arab Emirates.

OBJECTIVE: Schizophrenia is one of the most debilitating diseases in the United Arab Emirates. Oral antipsychotics (OA) are commonly used in terms of pharmacotherapy; however, these treatments can be rendered ineffective by poor patient adherence. Paliperidone palmitate once monthly (PP1M) is a long acting antipsychotic which can offer an adherence advantage when compared to oral treatments. The study objective is to estimate the cost effectiveness of PP1M in the UAE setting. RESEARCH DESIGN AND METHODS: A 1-year validated decision-tree model was adapted to the UAE setting using published literature and expert opinion. Patients on PP1M were compared with or without oral supplementation to patients on any oral antipsychotic. Patient outcomes studied were incremental cost per quality adjusted life years gained, incremental cost per hospitalizations, relapses, and emergency room visits averted. RESULTS: After 1 year, patients on PP1M monotherapy when compared to oral antipsychotics had better outcomes (0.840 vs 0.811 QALYs; 31 relapse days averted as well as 9 and 24 percentage points of ER and hospitalizations averted, respectively), and better healthcare savings (AED 1405). PP1M economically dominated oral antipsychotics. The results were stable across a broad range of deterministic and probabilistic sensitivity analyses. PP1M plus oral antipsychotics could not be evaluated due to the absence of clinical data that would provide insight into the clinical value of combination therapy. CONCLUSION: PP1M is estimated to save the UAE healthcare system money, while at the same time improving patient outcomes.

Increased cost of illness among European patients with type 2 diabetes treated with insulin.

OBJECTIVES: To investigate the association between outcomes and different escalating combinations of non-insulin medications vs. insulin. METHODS: Data were taken from the 2013 5EU NHWS, a cross-sectional survey including 62,000 respondents across France, Germany, Italy, Spain, and the UK. Costs were estimated from self-reported work impairment and healthcare visits using average wages and unit costs. Respondents taking antihyperglycemic medications (n = 2894) were compared according to treatment type using unadjusted comparisons followed by regression to adjust for confounders. RESULTS: Insulin users had the highest costs and worse outcomes, a pattern that remained after adjustment for a range of sociodemographic and disease characteristics. Incremental direct costs were approximately €800. Incremental indirect costs, applicable only to the employed, were larger than incremental direct costs, but were statistically significant only relative to non-insulin monotherapy. CONCLUSIONS: Escalation using oral agents rather than insulin is associated with better quality of life and lower costs, though these relationships may not be causal. Further research is warranted on escalation using oral agents among patients for whom insulin is not required.

Systematic review: treatment pattern and clinical effectiveness and safety of pharmaceutical therapies for Crohn's disease in Europe.

BACKGROUND: Although many clinical trials have been conducted in treatments of Crohn's disease (CD), whether the trial results were representative of daily practice needs to be supported by studies conducted in real-world settings. AIM: This study aims to identify how CD is treated and what are the clinical effectiveness and safety of the pharmaceutical therapies of CD in real-world settings. METHODS: A systematic literature review was conducted based on Medline®, Embase®, and Cochrane. All publications were assessed for title/abstract and full-text according to a predefined study protocol. Data were extracted and reported. RESULTS: A total of 1,998 publications were identified. Fifty studies including six publications reporting treatment pattern and 44 studies reporting clinical effectiveness and safety of pharmaceutical therapies in CD management in Europe were included. 5-Aminosalicylic acid and corticosteroids were reported to be used among 14%-74% of CD patients. Immunomodulators were used by 14%-25% and 29%-31% of CD patients as an initial and follow-up treatment, respectively. Biological therapies were used by 25%-33% of CD patients. A trend toward an increasing use of immunomodulators and biological therapies in Europe has been reported in recent years. Approximately 50% of patients achieved remission on immunomodulator or biologic treatment, although a relapse rate of up to 23% has been reported. CONCLUSION: There is a trend of treatment shift to immunomodulators and biologics in CD management. Clinical effectiveness of immunomodulators and biologics has been demonstrated, though with a lack of sustainability of the effectiveness.