RESUMEN
BACKGROUND: Irritable bowel syndrome (IBS) is common, and causes pain, bloating and diarrhoea and/or constipation. It is a troublesome condition that reduces the quality of life but causes no permanent damage. Inflammatory bowel disease (IBD) comprises mainly ulcerative colitis (UC) and Crohn's disease (CD). Both cause serious complications and may lead to sections of the bowel having to be removed, although this is more common with CD. The presenting symptoms of IBS and IBD can be similar. Distinguishing them on clinical signs and symptoms can be difficult. Until recently, colonoscopy was often required to rule out IBD. In younger people, > 60% of colonoscopies showed no abnormality. Faecal calprotectin (FC) is a protein released by the white blood cells, neutrophils, found in inflamed areas of the bowel in IBD. Determining the level of FC in stool samples may help distinguish IBS from IBD. OBJECTIVE: To review the value of FC for distinguishing between IBD and non-IBD. DATA SOURCES: Sources included MEDLINE, EMBASE, The Cochrane Library, Web of Science, websites of journals and the European Crohn's and Colitis Organisation (conference abstracts 2012 and 2013), and contact with experts. REVIEW METHODS: Systematic review and economic modelling. Review Manager (RevMan) version 5.2 (The Cochrane Collaboration, The Nordic Cochrane Centre, Copenhagen, Denmark) was used for most analysis, with statistical analyses done in Stata version 12 (StataCorp LP, College Station, TX, USA). Forest plots and receiver operating characteristic curves were produced. Quality Assessment of Diagnostic Accuracy Studies was used for quality assessment. Economic modelling was done in Microsoft Excel 2010 (Microsoft Corporation, Redmond, WA, USA). LIMITATIONS: Studies were often small, most used only one calprotectin cut-off level, and nearly all came from secondary care populations. RESULTS: Twenty-eight studies provided data for 2 × 2 tables and were included in meta-analyses, with seven in the most important comparison in adults (IBS vs. IBD) and eight in the key comparison in paediatrics (IBD vs. non-IBD). Most studies used laboratory enzyme-linked immunosorbent assay (ELISA) tests. For distinguishing between IBD and IBS in adults, these gave pooled sensitivity of 93% and specificity of 94% at FC cut-off level of 50 µg/g. Sensitivities at that cut-off ranged from 83% to 100%, and specificities from 60% to 100%. For distinguishing between IBD and non-IBD in paediatric populations with ELISA tests, sensitivities ranged from 95% to 100% at cut-off of 50 µg/g and specificities of 44-93%. Few studies used point-of-care testing but that seemed as reliable as ELISA, though perhaps less specific. The evidence did not provide any grounds for preferring one test over others on clinical effectiveness grounds. FC testing in primary care could reduce the need for referral and colonoscopies. Any quality-adjusted life-year gains are likely to be small because of the low prevalence of IBD and the high sensitivities of all of the tests, resulting in few false negatives with IBD. However, considerable savings could accrue. Areas of uncertainty include the optimum management of people with borderline results (50-150 µg/g), most of whom do not have IBD. Repeat testing may be appropriate before referral. CONCLUSIONS: Faecal calprotectin can be a highly sensitive way of detecting IBD, although there are inevitably trade-offs between sensitivity and specificity, with some false positives (IBS with positive calprotectin) if a low calprotectin cut-off is used. In most cases, a negative calprotectin rules out IBD, thereby sparing most people with IBS from having to have invasive investigations, such as colonoscopy. STUDY REGISTRATION: PROSPERO CRD 42012003287. FUNDING: The National Institute for Health Research Health Technology Assessment programme.
Asunto(s)
Colonoscopía/economía , Enfermedades Inflamatorias del Intestino/diagnóstico , Síndrome del Colon Irritable/diagnóstico , Complejo de Antígeno L1 de Leucocito/análisis , Adulto , Niño , Colonoscopía/efectos adversos , Análisis Costo-Beneficio , Bases de Datos Bibliográficas , Diagnóstico Diferencial , Ensayo de Inmunoadsorción Enzimática/economía , Heces/química , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/economía , Síndrome del Colon Irritable/complicaciones , Síndrome del Colon Irritable/economía , Complejo de Antígeno L1 de Leucocito/economía , Persona de Mediana Edad , Años de Vida Ajustados por Calidad de Vida , Sensibilidad y Especificidad , Reino UnidoRESUMEN
BACKGROUND: Advanced heart failure (HF) is a debilitating condition for which heart transplant (HT) offers the best treatment option. However, the supply of donor hearts is diminishing and demand greatly exceeds supply. Ventricular assist devices (VADs) are surgically implanted pumps used as an alternative to transplant (ATT) or as a bridge to transplant (BTT) while a patient awaits a donor heart. Surgery and VADs are costly. For the NHS to allocate and deliver such services in a cost-effective way the relative costs and benefits of these alternative treatments need to be estimated. OBJECTIVES: To investigate for patients aged ≥ 16 years with advanced HF eligible for HT: (1) the clinical effectiveness and cost-effectiveness of second- and third-generation VADs used as BTT compared with medical management (MM); and (2) the clinical effectiveness and cost-effectiveness of second- and third-generation VADs used as an ATT in comparison with their use as BTT therapy. DATA SOURCES: Searches for clinical effectiveness studies covered years from 2003 to March 2012 and included the following data bases: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE), NHS Economic Evaluation Database (NHS EED), HTA databases [NHS Centre for Reviews and Dissemination (CRD)], Science Citation Index and Conference Proceedings (Web of Science), UK Clinical Research Network (UKCRN) Portfolio Database, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO and National Library of Medicine (NLM) Gateway, Cochrane Central Register of Controlled Trials (CENTRAL), Current Controlled Trials and ClinicalTrials.gov. Reference lists of relevant articles were checked, and VAD manufacturers' websites interrogated. For economic analyses we made use of individual patient data (IPD) held in the UK Blood and Transplant Database (BTDB). REVIEW METHODS: Systematic reviews of evidence on clinical effectiveness and cost-effectiveness of second- and third-generation US Food and Drug Administration (FDA) and/or Conformité Européenne (CE) approved VADs. Publications from the last 5 years with control groups, or case series with 50 or more patients were included. Outcomes included survival, functional capacity (e.g. change in New York Heart Association functional classification), quality of life (QoL) and adverse events. Data from the BTDB were obtained. A discrete-time, semi-Markov, multistate model was built. Deterministic and probabilistic methods with multiple sensitivity analyses varying survival, utilities and cost inputs to the model were used. Model outputs were incremental cost-effectiveness ratios (ICERs), cost/quality-adjusted life-years (QALYs) gained and cost/life-year gained (LYG). The discount rate was 3.5% and the time horizon varied over 3 years, 10 years and lifetime. RESULTS: Forty publications reported clinical effectiveness of VADs and one study reported cost-effectiveness. We found no high-quality comparative empirical studies of VADs as BTT compared with MM or as ATT compared with BTT. Approximately 15-25% of the patients receiving a device had died by 12 months. Studies reported the following wide ranges for adverse events: 4-27% bleeding requiring transfusion; 1.5-40% stroke; 3.3-48% infection; 1-14% device failure; 3-30% HF; 11-32% reoperation; and 3-53% renal failure. QoL and functional status were reported as improved in studies of two devices [HeartMate II (HMII; Thoratec Inc., Pleasanton, CA, USA) and HeartWare (HW; HeartWare Inc., Framingham, MA, USA)]. At 3 years, 10 years and lifetime, the ICERs for VADs as BTT compared with MM were £122,730, £68,088 and £55,173 respectively. These values were stable to changes in survival of the MM group. Both QoL and costs were reduced by VADs as ATT compared with VADs as BTT giving ICERs in south-west quadrant of the cost effectiveness plain (cost saving/QALY sacrificed) of £353,467, £31,685 and £20,637 over the 3 years, 10 years and lifetime horizons respectively. Probabilistic analyses yielded similar results for both research questions. LIMITATIONS: Conclusions about the clinical effectiveness were limited by the lack of randomised controlled trials (RCTs) comparing the effectiveness of different VADs for BTT or comparing BTT with any alternative treatment and by the overlapping populations in published studies. Although IPD from the BTDB was used to estimate the cost-effectiveness of VADs compared with MM for BTT, the lack of randomisation of populations limited the interpretation of this analysis. CONCLUSIONS: At 3 years, 10 years and lifetime the ICERs for VADs as BTT compared with MM are higher than generally applied willingness-to-pay thresholds in the UK, but at a lifetime time horizon they approximate threshold values used in end of life assessments. VADs as ATT have a reduced cost but cause reduced QALYs relative to BTT. Future research should direct attention towards two areas. First, how any future evaluations of second- or third-generation VADs might be conducted. For ethical reasons a RCT offering equal probability of HT for each group would not be feasible; future studies should fully assess costs, long-term patient survival, QoL, functional ability and adverse events, so that these may be incorporated into economic evaluation agreement on outcomes measures across future studies. Second, continuation of accurate data collection in the UK database to encompass QoL data and comparative assessment of performance with other international centres. FUNDING: The National Institute for Health Research Health Technology Assessment programme.
Asunto(s)
Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/terapia , Corazón Auxiliar/economía , Factores de Edad , Cardiotónicos/economía , Cardiotónicos/uso terapéutico , Análisis Costo-Beneficio , Corazón Auxiliar/efectos adversos , Humanos , Modelos Económicos , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Medicina Estatal , Evaluación de la Tecnología Biomédica , Reino UnidoRESUMEN
BACKGROUND: Spinal metastases can lead to significant morbidity and reduction in quality of life due to spinal cord compression (SCC). Between 5% and 20% of patients with spinal metastases develop metastatic spinal cord compression during the course of their disease. An early study estimated average survival for patients with SCC to be between 3 and 7 months, with a 36% probability of survival to 12 months. An understanding of the natural history and early diagnosis of spinal metastases and prediction of collapse of the metastatic vertebrae are important. OBJECTIVES: To undertake a systematic review to examine the natural history of metastatic spinal lesions and to identify patients at high risk of vertebral fracture and SCC. DATA SOURCES: The search strategy covered the concepts of metastasis, the spine and adults. Searches were undertaken from inception to June 2011 in 13 electronic databases [MEDLINE; MEDLINE In-Process & Other Non-Indexed Citations; EMBASE; Cochrane Database of Systematic Reviews; Cochrane Central Register of Controlled Trials (CENTRAL); Database of Abstracts of Reviews of Effects (DARE), NHS Economic Evaluation Database (NHS EED), HTA databases (NHS Centre for Reviews and Dissemination); Science Citation Index and Conference Proceedings (Web of Science); UK Clinical Research Network (UKCRN) Portfolio Database; Current Controlled Trials; ClinicalTrials.gov]. REVIEW METHODS: Titles and abstracts of retrieved studies were assessed by two reviewers independently. Disagreement was resolved by consensus agreement. Full data were extracted independently by one reviewer. All included studies were reviewed by a second researcher with disagreements resolved by discussion. A quality assessment instrument was used to assess bias in six domains: study population, attrition, prognostic factor measurement, outcome measurement, confounding measurement and account, and analysis. Data were tabulated and discussed in a narrative review. Each tumour type was looked at separately. RESULTS: In all, 2425 potentially relevant articles were identified, of which 31 met the inclusion criteria. No study examined natural history alone. Seventeen studies reported retrospective data, 10 were prospective studies, and three were other study designs. There was one systematic review. There were no randomised controlled trials (RCTs). Approximately 5782 participants were included. Sample sizes ranged from 41 to 859. The age of participants ranged between 7 and 92 years. Types of cancers reported on were lung alone (n= 3), prostate alone (n= 6), breast alone (n= 7), mixed cancers (n= 13) and unclear (n= 1). A total of 93 prognostic factors were identified as potentially significant in predicting risk of SCC or collapse. Overall findings indicated that the more spinal metastases present and the longer a patient was at risk, the greater the reported likelihood of development of SCC and collapse. There was an increased risk of developing SCC if a cancer had already spread to the bones. In the prostate cancer studies, tumour grade, metastatic load and time on hormone therapy were associated with increased risk of SCC. In one study, risk of SCC before death was 24%, and 2.37 times greater with a Gleason score ≥ 7 than with a score of < 7 (p= 0.003). Other research found that patients with six or more bone lesions were at greater risk of SCC than those with fewer than six lesions [odds ratio (OR) 2.9, 95% confidence interval (CI) 1.012 to 8.35, p= 0.047]. For breast cancer patients who received a computerised tomography (CT) scan for suspected SCC, multiple logistic regression in one study identified four independent variables predictive of a positive test: bone metastases ≥ 2 years (OR 3.0 95% CI 1.2 to 7.6; p= 0.02); metastatic disease at initial diagnosis (OR 3.4, 95% CI 1.0 to 11.4; p= 0.05); objective weakness (OR 3.8, 95% CI 1.5 to 9.5; p= 0.005); and vertebral compression fracture on spine radiograph (OR 2.6, 95% CI 1.0 to 6.5; p= 0.05). A further study on mixed cancers, among patients who received surgery for SCC, reported that vertebral body compression fractures were associated with presurgery chemotherapy (OR 2.283, 95% CI 1.064 to 4.898; p= 0.03), cancer type [primary breast cancer (OR 4.179, 95% CI 1.457 to 11.983; p= 0.008)], thoracic involvement (OR 3.505, 95% CI 1.343 to 9.143; p= 0.01) and anterior cord compression (OR 3.213, 95% CI 1.416 to 7.293; p= 0.005). LIMITATIONS: Many of the included studies provided limited information about patient populations and selection criteria and they varied in methodological quality, rigour and transparency. Several studies identified type of cancer (e.g. breast, lung or prostate cancer) as a significant factor in predicting SCC, but it remains difficult to determine the risk differential partly because of residual bias. Consideration of quantitative results from the studies does not easily allow generation of a coherent numerical summary, studies were heterogeneous especially with regard to population, results were not consistent between studies, and study results almost universally lacked corroboration from other independent studies. CONCLUSION: No studies were found which examined natural history. Overall burden of metastatic disease, confirmed metastatic bone involvement and immediate symptomatology suggestive of spinal column involvement are already well known as factors for metastatic SCC, vertebral collapse or progression of vertebral collapse. Although we identified a large number of additional possible prognostic factors, those which currently offer the most potential are unclear. Current clinical consensus favours magnetic resonance imaging and CT imaging modalities for the investigation of SCC and vertebral fracture. Future research should concentrate on: (1) prospective randomised designs to establish clinical and quality-of-life outcomes and cost-effectiveness of identification and treatment of patients at high risk of vertebral collapse and SCC; (2) Service Delivery and Organisation research on magnetic resonance imaging (MRI) scans and scanning (in tandem with research studies on use of MRI to monitor progression) in order to understand best methods for maximising use of MRI scanners; and (3) investigation of prognostic algorithms to calculate probability of a specified event using high-quality prospective studies, involving defined populations, randomly selected and clearly identified samples, and with blinding of investigators. FUNDING: This report was commissioned by the National Institute for Health Research Health Technology Assessment Programme NIHR HTA Programme as project number HTA 10/91/01.
Asunto(s)
Compresión de la Médula Espinal/etiología , Fracturas de la Columna Vertebral/etiología , Neoplasias de la Columna Vertebral/secundario , Neoplasias de la Mama/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Metástasis de la Neoplasia/patología , Neoplasias de la Próstata/patología , Factores de Riesgo , Neoplasias de la Columna Vertebral/complicaciones , Neoplasias de la Columna Vertebral/diagnóstico , Neoplasias de la Columna Vertebral/patologíaRESUMEN
BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) has been increasing, owing to increases in overweight and obesity, decreasing physical activity and the changing demographic structure of the population. People can develop T2DM without symptoms and up to 20% may be undiagnosed. They may have diabetic complications, such as retinopathy, by the time they are diagnosed, or may suffer a heart attack, without warning. Undiagnosed diabetes can be detected by raised blood glucose levels. AIM: The aim of this review was to provide an update for the UK National Screening Committee (NSC) on screening for T2DM. METHODS: As this review was undertaken to update a previous Health Technology Assessment review published in 2007, and a more recent Scottish Public Health Network review, searches for evidence were restricted from 2009 to end of January 2012, with selected later studies added. The databases searched were MEDLINE, EMBASE, MEDLINE-in-Process & Other Non-Indexed Citations, Science Citation Index and Conference Proceedings Citation Index. The case for screening was considered against the criteria used by the NSC to assess proposed population screening programmes. RESULTS: Population screening for T2DM does not meet all of the NSC criteria. Criterion 12, on optimisation of existing management, has not been met. A report by the National Audit Office (NAO) gives details of shortcomings. Criterion 13 requires evidence from high-quality randomised controlled trials that screening is beneficial. This has not been met. The Ely trial of screening showed no benefit. The ADDITION trial was not a trial of screening, but showed no benefit in cardiovascular outcomes from intensive management in people with screen-detected T2DM. Criterion 18 on staffing and facilities does not appear to have been met, according to the NAO report. Criterion 19 requires that all other options, including prevention, should have been considered. A large proportion of cases of T2DM could be prevented if people avoided becoming overweight or obese. The first stage of selection would use risk factors, using data held on general practitioner computer systems, using the QDiabetes Risk Score, or by sending out questionnaires, using the Finnish Diabetes Risk Score (FINDRISC). Those at high risk would have a measure of blood glucose. There is no perfect screening test. Glycated haemoglobin (HbA1c) testing has advantages in not requiring a fasting sample, and because it is a predictor of vascular disease across a wider range than just the diabetic one. However, it lacks sensitivity and would miss some people with diabetes. Absolute values of HbA1c may be more useful as part of overall risk assessment than a dichotomous 'diabetes or not diabetes' diagnosis. The oral glucose tolerance test is more sensitive, but inconvenient, more costly, has imperfect reproducibility and is less popular, meaning that uptake would be lower. CONCLUSIONS: When considered against the NSC criteria, the case for screening is less strong than it was in the 2007 review. The main reason is the absence of cardiovascular benefit in the two trials published since the previous review. There is a case for selective screening as part of overall vascular risk assessment. Population screening for T2DM does not meet all of the NSC criteria. FUNDING: The National Institute for Health Research Health Technology Assessment programme.
Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Complicaciones de la Diabetes/prevención & control , Diabetes Mellitus Tipo 2/diagnóstico , Tamizaje Masivo/normas , Síndrome Metabólico , Obesidad/complicaciones , Estado Prediabético/diagnóstico , Adulto , Distribución por Edad , Anciano , Índice de Masa Corporal , Enfermedades Cardiovasculares/economía , Enfermedades Cardiovasculares/etiología , Análisis Costo-Beneficio , Complicaciones de la Diabetes/economía , Diabetes Mellitus Tipo 2/economía , Diabetes Mellitus Tipo 2/prevención & control , Femenino , Prueba de Tolerancia a la Glucosa/economía , Prueba de Tolerancia a la Glucosa/normas , Hemoglobina Glucada/análisis , Hemoglobina Glucada/economía , Humanos , Incidencia , Masculino , Tamizaje Masivo/economía , Tamizaje Masivo/métodos , Síndrome Metabólico/complicaciones , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/economía , Síndrome Metabólico/prevención & control , Persona de Mediana Edad , Obesidad/economía , Estado Prediabético/complicaciones , Estado Prediabético/economía , Prevalencia , Medición de Riesgo , Reino UnidoRESUMEN
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is closely linked with obesity and the prevalence of NAFLD is about 17% to 33% in the Western world. There is a strong association of NAFLD with insulin resistance and, hence, insulin sensitisers have been tried. This systematic review examined the clinical effectiveness of insulin sensitisers in patients with NAFLD, to help decide whether or not a trial or trials of the insulin sensitisers was necessary and also to explore whether or not non-invasive alternatives to liver biopsy were available that could be used in a large trial of the insulin sensitisers. OBJECTIVE: To review the use of insulin sensitisers in the treatment of NAFLD. REVIEW METHODS: A systematic review of the clinical effectiveness of metformin, rosiglitazone and pioglitazone was carried out, including reviews and randomised controlled trials (RCTs). Databases searched were MEDLINE, 1950 to June 2010; EMBASE, 1980 to June 2010; Science Citation Index Expanded, June 2010; Conference Proceedings Citation Index - Science June 2010; The Cochrane Library 2005-10. Abstracts were screened independently by two researchers. A narrative review of diagnostic methods was conducted. RESULTS: Clinical effectiveness. We identified 15 RCTs (one available as abstract). Four papers explored efficacy of pioglitazone, one rosiglitazone, eight metformin; two compared metformin and rosiglitazone, although one used both metformin and rosiglitazone. The duration of most trials was between 6 and 12 months. Many trials had a small number of participants and the quality of the studies was mixed. Pioglitazone improved all parameters of liver histology. Metformin showed mixed results, with ultrasound changes in two studies showing some improvement in steatosis, whereas there were no changes in the other two. Metformin, however, showed no improvement in non-alcoholic steatohepatitis (NASH) stages. Metformin showed greater reduction in glycosylated haemoglobin (-0.23% to -1.2% vs -0.2% to -0.7%) and fasting plasma glucose (+0.05 to -3.19 mmol/l vs -0.17 to -1.11 mmol/l) compared with pioglitazone. Metformin led to weight reduction (-4.3 to -6.7 kg), whereas participants on pioglitazone gained weight (+2.5 to +4.7 kg). Alanine aminotransferase levels were reduced with both metformin and pioglitazone; however, the reduction in levels with pioglitazone was not different to that caused by vitamin E. Most studies suggested that metformin led to a significant reduction in insulin resistance. Diagnosis. Non-invasive methods of diagnosing NAFLD without liver biopsy, using combinations of clinical history, laboratory tests and ultrasound, have been explored, but so far liver biopsy is the only proven method of distinguishing simple steatosis from NASH. Transient elastography appears useful, but less so in obese individuals. Magnetic resonance spectroscopy shows promise, but is expensive and not readily available. LIMITATIONS: Mixed quality of trials, with lack of detail as to how some trials were conducted. Many trials had small numbers of patients. CONCLUSIONS: The main need for drug trials is at the NASH stage. However, at present, any trial in the more advanced forms of NAFLD would have to use liver biopsy. The highest priority for research may, therefore, be in the diagnosis of NAFLD, and the differentiation between steatosis and NASH. The newer agents, the glucagon-like peptide-1 analogues such as liraglutide, may be more worthy of a trial. FUNDING: The National Institute for Health Research Health Technology Assessment programme.
Asunto(s)
Hígado Graso/tratamiento farmacológico , Resistencia a la Insulina/fisiología , Metformina/uso terapéutico , Tiazolidinedionas/uso terapéutico , Biopsia , Bases de Datos Bibliográficas , Diagnóstico Diferencial , Hígado Graso/diagnóstico , Hígado Graso/economía , Humanos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Hígado/patología , Metformina/farmacología , Enfermedad del Hígado Graso no Alcohólico , Pioglitazona , Ensayos Clínicos Controlados Aleatorios como Asunto , Literatura de Revisión como Asunto , Rosiglitazona , Tiazolidinedionas/farmacología , Pérdida de Peso/efectos de los fármacos , Pérdida de Peso/fisiologíaRESUMEN
This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of liraglutide in the treatment of type 2 diabetes mellitus, based upon the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The manufacturer proposed the use of liraglutide as a second or third drug in patients with type 2 diabetes whose glycaemic control was unsatisfactory with metformin, with or without a second oral glucose-lowering drug. The submission included six manufacturer-sponsored trials that compared the efficacy of liraglutide against other glucose-lowering agents. Not all of the trials were relevant to the decision problem. The most relevant were Liraglutide Effects and Actions in Diabetes 5 (LEAD-5) (liraglutide used as part of triple therapy and compared against insulin glargine) and LEAD-6 [liraglutide in triple therapy compared against another glucagon-like peptide-1 agonist, exenatide]. Five of the six trials were published in full and one was then unpublished. Two doses of liraglutide, 1.2 and 1.8 mg, were used in some trials, but in the two comparisons in triple therapy, against glargine and exenatide, only the 1.8-mg dose was used. Liraglutide in both doses was found to be clinically effective in lowering blood glucose concentration [glycated haemoglobin (HbA1c)], reducing weight (unlike other glucose-lowering agents, such as sulphonylureas, glitazones and insulins, which cause weight gain) and also reducing systolic blood pressure (SBP). Hypoglycaemia was uncommon. The ERG carried out meta-analyses comparing the 1.2- and 1.8-mg doses of liraglutide, which suggested that there was no difference in control of diabetes, and only a slight difference in weight loss, insufficient to justify the extra cost. The cost-effectiveness analysis was carried out using the Center for Outcomes Research model. The health benefit was reported as quality-adjusted life-years (QALYs). The manufacturer estimated the cost-effectiveness to be £ 15,130 per QALY for liraglutide 1.8 mg compared with glargine, £ 10,054 per QALY for liraglutide 1.8 mg compared with exenatide, £ 10,465 per QALY for liraglutide 1.8 mg compared with sitagliptin, and £ 9851 per QALY for liraglutide 1.2 mg compared with sitagliptin. The ERG conducted additional sensitivity analyses and concluded that the factors that carried most weight were: in the comparison with glargine, the direct utility effects of body mass index (BMI) changes and SBP, with some additional contribution from HbA1c, in the comparison with exenatide, HbA1c, with some additional effects from cholesterol and triglycerides in the comparison with sitagliptin, HbA1c and direct utility effects of BMI changes. The European Medicines Agency has approved liraglutide in dual therapy with other oral glucose-lowering agents. NICE guidance recommends the use of liraglutide 1.2 mg in triple therapy when glycaemic control remains or becomes inadequate with a combination of two oral glucose-lowering drugs. The use of liraglutide 1.2 mg in a dual therapy is indicated only in patients who are intolerant of, or have contraindications to, three oral glucose-lowering drugs. The use of liraglutide 1.8 mg was not approved by NICE. The ERG recommends research into the (currently unlicensed) use of liraglutide in combination with long-acting insulin.