Original Title: État des connaissances - La pharmacothérapie dans le traitement de l'obésité

Authors' objectives: As part of its work on the organization of care and services in bariatric medicine and, more generally, on obesity, the Ministère de la Santé et des Services sociaux asked the Institut national d'excellence en santé et en services sociaux to produce a state-of-knowledge report on the efficacy, safety, cost-effectiveness and recommended use of drugs for the treatment of obesity, in order to support it in its deliberation on the advisability of extending public coverage to such drugs for certain well-defined categories of patients. This report presents the current state of knowledge on four drugs approved by Health Canada for the treatment of obesity, namely, semaglutide, liraglutide, orlistat and naltrexone/bupropion, and on tirzepatide, which has not yet been approved by Health Canada, but which is marketed in other parts of the world, including the United States, for the treatment of type 2 diabetes and which is currently being investigated for the treatment of obesity.

Authors' results and conclusions: RESULTS: (#1: Drugs effective for short-term weight loss when used in conjunction with lifestyle modification): In the case of people living with obesity, the literature review yielded the following findings regarding the use of anti-obesity drugs in conjunction with lifestyle modification compared to lifestyle modification alone: • In adults, semaglutide, liraglutide, tirzepatide, orlistat and naltrexone/bupropion reduce weight in a statistically significant manner (moderate to high level of scientific evidence). Depending on the drug used, the mean weight loss observed with pharmacotherapy can be 3% to 17% greater than with lifestyle modification alone. In addition, a statistically significant improvement in the quality of life score is observed with all of these drugs (moderate to high level of scientific evidence), except orlistat (moderate level of scientific evidence) and tirzepatide (insufficient level of evidence). In young people aged 12 to 18 years, orlistat and liraglutide combined with lifestyle modification lead to a statistically significant reduction in weight or weight gain and body mass index (moderate level of scientific evidence). • The following cardiometabolic parameters are statistically significantly improved with anti-obesity drugs in adults: blood pressure (semaglutide, liraglutide, tirzepatide and orlistat), the glycated hemoglobin level (liraglutide and orlistat), and the low-density lipoprotein cholesterol (LDL-C) level (tirzepatide and orlistat) (low to moderate level of scientific evidence). In young people aged 12 to 18 years, a statistically significant decrease in the glycated hemoglobin level is observed with liraglutide (moderate level of scientific evidence). • In adults, there is a statistically significant increase in the risk of gastrointestinal adverse effects with all of the anti-obesity drugs examined (moderate level of scientific evidence), but there is no statistically significant difference in the risk of severe gastrointestinal adverse effect (low to moderate level of scientific evidence), with the exception of a statistically significant increase with tirzepatide 10 mg and 15 mg (moderate level of scientific evidence). A statistically significant increase in the risk of treatment discontinuation due to adverse effects is observed with all the anti-obesity drugs examined (moderate to high level of scientific evidence). (#2: Additional tools concerning people living with severe obesity that is having a significant impact on their health): The learned societies and the clinicians consulted recommend that pharmacotherapy for obesity be part of a set of interventions that includes lifestyle modification, dietary changes, physical activity, and behavioural interventions. • According to the clinicians consulted, access to a multidisciplinary team specializing in obesity treatment is essential for the success of any intervention aimed at durable weight loss. • Only Australia and the United Kingdom (with the exception of Scotland) cover certain anti-obesity drugs, but generally only for adults with a body mass index (BMI) ≥ 35 kg/m2 and an obesity-related comorbidity. In the United Kingdom, liraglutide and semaglutide are covered only if prescribed by specialized, multidisciplinary level 3 or 4 weight management services. Semaglutide is currently being evaluated for coverage purposes in several jurisdictions (e.g., France, Scotland and the United States). Tirzepatide is not covered in any jurisdiction, but it has not yet been approved by health authorities for use in the treatment of obesity. Currently, no country covers the pediatric use of antiobesity drugs. CONCLUSION: The findings of this report have made it possible to assess the role that pharmacotherapy could play in the treatment of obesity in adults and children. They will also help the Ministère de la Santé et des Services sociaux (MSSS) consider the advisability of removing drugs prescribed for the treatment of obesity from the list of exclusions of the public prescription drug insurance plan. In such case, a more thorough and focused evaluation will have to be carried out by the Institut national d'excellence en santé et en services sociaux using the processes established by the Direction de l'évaluation des médicaments et des technologies à fins de remboursement. In fact, to determine whether these drugs should be covered by the public prescription drug insurance plan, and under what conditions, the INESSS will need to assess their overall value and make recommendations to the minister. In addition, despite the potential contribution of pharmacotherapy, the organization of multidisciplinary services for the management of obesity appears essential for providing an adequate follow-up, regardless of the intervention proposed.

Authors' methods: A systematic review of the scientific and pharmacoeconomic literature and of publications containing positions, recommendations and guidelines from learned societies and other organizations was carried out in accordance with preestablished criteria. Contextual information and the perspective of clinicians from the medical specialties concerned were gathered as well. In the systematic literature review carried out in this project, the efficacy, safety and cost-effectiveness of five drugs used in the treatment of obesity were evaluated with regard to the following main parameters: weight loss, the effect on cardiometabolic markers, the effect on quality of life, gastrointestinal adverse effects, discontinuation due to adverse effects, cost and the incremental cost-effectiveness ratio.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/la-pharmacotherapie-dans-le-traitement-de-lobesite.html

Year Published: 2022

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/la-pharmacotherapie-dans-le-traitement-de-lobesite.html

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: L'Institut national d'excellence en sante et en services sociaux (INESSS)