Original Title: Sibutramina para o tratamento dos pacientes com obesidade

Authors' objectives: Is sibutramine effective and safe for the treatment of obese adult patients, who do not respond to non-pharmacological treatment and do not have cardiovascular disease?

Authors' results and conclusions: The CONITEC’s members present at the 86th Ordinary Meeting decided not to recommend the incorporation of sibutramine for the treatment of obese patients. The Deliberation Record No. 513/2020 was signed.

Authors' recommendations: Scientific evidence: In the report prepared by SCTIE/Ministry of Health of Brazil, 14 studies were included: three systematic reviews, ten randomized controlled trials (RCTs), and one cohort study. The three systematic reviews were assessed as high risk of bias. The RCTs were assessed using the Cochrane risk of bias tool, most of which were classified as high risk or unclear risk. The cohort study was classified as low risk, according to respective assessment tool. In the critical analysis of the Technical Dossier prepared by ABESO, 13 studies were included: ten RCTs, and three cohort studies. According to the evidence presented by both applicants, sibutramine has been shown to be effective in achieving clinically significant weight loss, as well as in reducing body mass index and waist circumference, especially when compared with placebo, and in short and medium term. In the long term, there is evidence that indicates a weight regain and low persistence. In most studies, sibutramine was used in conjunction with the recommendation to change eating habits and behaviors. The main adverse events associated with the use of sibutramine were dry mouth, constipation and insomnia. Increased blood pressure and heart rate were also reported, but to a lesser extent. RCTs and cohort studies included in the critical analysis had a high risk or unclear risk of bias. Budget impact analysis: In SCTIE’s report, the pharmaceutical forms registered with ANVISA, sibutramine 10 and 15 mg capsules, were considered to estimate the cost of treatment. The costs were limited to the purchase price of medicines. As no data were found in the literature on the percentage of patients receiving daily doses of 10 and 15 mg, it was decided to develop six scenarios: a scenario where all patients receive daily doses of 10 mg; a scenario where all patients receive daily doses of 15 mg; a scenario where half of patients receive daily doses 10 mg; and other three scenarios where patient population would be excluded due to some contraindications (cardiovascular diseases; diabetes and arterial hypertension; and uncontrolled hypertension). The analysis was conducted over a five-year time horizon, assuming an initial market share of 30% for sibutramine, with annual increments of the same value, reaching 50% in the fifth year. Thus, in these six scenarios, the budget impact of incorporating sibutramine would range from BRL 3.3 to BRL 4.3 billion in the first year, and from BRL 22.7 to BRL 29.6 billion after five years. Based on the lowest price of public procurement during six months of the current year, recent data on the eligible population, and other premises of the previous scenarios, the budget impact of incorporating sibutramine was estimated to range from BRL 1.4 to BRL 1.7 billion in the first year, and from BRL 9.3 to BRL 11.8 billion after five years. Three other scenarios were developed, based on these updated price and population data, but excluding patients who underwent stomach reduction surgery, patients without significant weight loss, and patients with cardiovascular diseases (except hypertension), diabetes and arterial hypertension, or uncontrolled arterial hypertension, and considering persistence rate and market share of 100%. In these scenarios, the amounts would be BRL 6.4, BRL 5.6 and BRL 5.8 billion, respectively. In ABESO’s Technical Dossier, the budget impact over five years would range from BRL 542.3 to BRL 902.5 million, considering different values of effectiveness. Varying the market share and the highest and lowest effectiveness value, the amounts may reach BRL 1.8 billion. Considering the efficacy values of sibutramine, the reduction in the incidence of diabetes cases, and discounting the value of sibutramine, the budget impact would result in savings ranging from BRL 769.5 million to BRL 2.9 billion. However, the results in the ABESO’s Technical Dossier may be under or overestimated, due to uncertainties and limitations in the parameters and assumptions used in the budget impact analysis, as well as the impossibility of verifying and reproducing the calculations used, so compromising the understanding of the financial consequences of incorporating sibutramine in the scope of SUS. Considerations: The available evidence suggests that treatment with sibutramine for weight loss is clinically relevant for obese patients. However, there are uncertainties about the benefits of sibutramine due to factors such as low methodological quality of the studies, trend of weight regain over time as well as trend of publishing positive results, and also a significant number of adverse events and persistence of use. Although available in Brazil, sibutramine has been withdrawn from the market in many countries.

Project Status: Completed

URL for project: http://conitec.gov.br/images/Consultas/Relatorios/EN2020/20200915_Report522_Sibutramine_ObesePatients.pdf

Year Published: 2020

URL for published report: http://conitec.gov.br/images/Relatorios/2020/Relatorio_sibutramina_obesidade_522_2019_FINAL.pdf

URL for additional information: http://conitec.gov.br/recomendation-reports

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Brazil

Organisation Name: National Committee for Technology Incorporation (CONITEC)

Contact Address: Esplanada dos Ministérios, Bl. G, Ed. Sede, 8º andar, CEP: 70058-900

Contact Name: Clarice Moreira Portugal

Contact Email: clarice.portugal@saude.gov.br

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