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Cited by 944Pharmacology and Obesity TreatmentBlood Pressure and Hypertension StudiesCardiovascular Function and Risk Factors

Effect of Sibutramine on Cardiovascular Outcomes in Overweight and Obese Subjects

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James, W. Philip T., Caterson, Ian D., Coutinho, Walmir, Finer, Nick, Van Gaal, Luc F., Maggioni, Aldo P., Torp-Pedersen, Christian, Sharma, Arya M. +3 more·2010·New England Journal of Medicine
DOI 10.1056/nejmoa1003114
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Abstract

BACKGROUND: The long-term effects of sibutramine treatment on the rates of cardiovascular events and cardiovascular death among subjects at high cardiovascular risk have not been established. METHODS: We enrolled in our study 10,744 overweight or obese subjects, 55 years of age or older, with preexisting cardiovascular disease, type 2 diabetes mellitus, or both to assess the cardiovascular consequences of weight management with and without sibutramine in subjects at high risk for cardiovascular events. All the subjects received sibutramine in addition to participating in a weight-management program during a 6-week, single-blind, lead-in period, after which 9804 subjects underwent random assignment in a double-blind fashion to sibutramine (4906 subjects) or placebo (4898 subjects). The primary end point was the time from randomization to the first occurrence of a primary outcome event (nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death). RESULTS: The mean duration of treatment was 3.4 years. The mean weight loss during the lead-in period was 2.6 kg; after randomization, the subjects in the sibutramine group achieved and maintained further weight reduction (mean, 1.7 kg). The mean blood pressure decreased in both groups, with greater reductions in the placebo group than in the sibutramine group (mean difference, 1.2/1.4 mm Hg). The risk of a primary outcome event was 11.4% in the sibutramine group as compared with 10.0% in the placebo group (hazard ratio, 1.16; 95% confidence interval [CI], 1.03 to 1.31; P=0.02). The rates of nonfatal myocardial infarction and nonfatal stroke were 4.1% and 2.6% in the sibutramine group and 3.2% and 1.9% in the placebo group, respectively (hazard ratio for nonfatal myocardial infarction, 1.28; 95% CI, 1.04 to 1.57; P=0.02; hazard ratio for nonfatal stroke, 1.36; 95% CI, 1.04 to 1.77; P=0.03). The rates of cardiovascular death and death from any cause were not increased. CONCLUSIONS: Subjects with preexisting cardiovascular conditions who were receiving long-term sibutramine treatment had an increased risk of nonfatal myocardial infarction and nonfatal stroke but not of cardiovascular death or death from any cause. (Funded by Abbott; ClinicalTrials.gov number, NCT00234832.)

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Crossref · 10.1056/nejmoa1003114

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  • Early weight loss medications fenfluramine and sibutramine were withdrawn due to severe cardiovascular and psychiatric side effects.

    “Early weight loss medications, such as fenfluramine (Fen-Phen) and sibutramine, were withdrawn due to severe cardiovascular and psychiatric side effects [3,4].”

    From Obesity: Clinical Impact, Pathophysiology, Complications, and Modern Innovations in Therapeutic Strategies (2025) · cites this paper as [4]

    The Results (p. 1) report higher rates of nonfatal myocardial infarction and stroke with sibutramine, supporting the cardiovascular-risk part of the claim. The paper does not say sibutramine was withdrawn because of those risks, and the passages do not establish psychiatric side effects or address fenfluramine. (LLM, conf=0.84)

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  • Sibutramine was discontinued in 2010 after the SCOUT trial showed elevated cardiovascular events such as stroke in high-risk patients.

    “Despite 5–10% weight loss in trials, it was discontinued in 2010 after the SCOUT trial showed elevated cardiovascular events (e.g., stroke) in high-risk patients [4].”

    From Obesity: Clinical Impact, Pathophysiology, Complications, and Modern Innovations in Therapeutic Strategies (2025) · cites this paper as [4]

    The Results (p. 1) report more cardiovascular events, including nonfatal strokes, with sibutramine than with placebo in the high-risk SCOUT population. The paper does not report that sibutramine was discontinued in 2010, and its reported weight changes do not establish the citing sentence’s 5–10% weight-loss figure. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The concept of treating obesity to reduce the risk of cardiovascular complications has been hampered by the lack of evidence from trials indicating that lifestyle or pharmacologic interventions for overweight or obesity improve cardiovascular outcomes.

    “the concept of treating obesity to reduce the risk of cardiovascular complications has been hampered by the lack of evidence from trials indicating that lifestyle or pharmacologic interventions for overweight or obesity improve cardiovascular outcomes. 11-15”

    From Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (2023) · cites this paper as [13]

  • Prospective studies that evaluated the effect of nonsurgical weight loss interventions on cardiovascular event reduction have been disappointing.

    “Prospective studies that evaluated the effect of nonsurgical weight loss interventions on CV event reduction have been disappointing [4, 5, 6, 7, 8].”

    From Semaglutide for cardiovascular event reduction in people with overweight or obesity: <scp>SELECT</scp> study baseline characteristics (2023) · cites this paper as [5]

  • Across the obesity CVOTs, SELECT is the only study to our knowledge that only enrolled participants with established CVD, whereas in the other obesity CVOTs, 24.9% to 50.5% of participants had no prior events.

    “Specifically, across the obesity CVOTs, SELECT is the only study to our knowledge that only enrolled participants with established CVD, whereas in the other obesity CVOTs, 24.9% to 50.5% of participants had no prior events [5, 6, 7, 8].”

    From Semaglutide for cardiovascular event reduction in people with overweight or obesity: <scp>SELECT</scp> study baseline characteristics (2023) · cites this paper as [5]

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Research works printed but not linked: 5

  1. [3]3. loss maintenance. Annu Rev Nutr 2001; 21:323-41. - Lean M, Finer N. ABC of obesity.
  2. [9]9. diabetic diets in the 1980s. Lancet 1986; 1:723-5. - Heart Protection Study. Collaborative
  3. [14]14. Study Group. Randomized trial of choles- - terol lowering in 4444 patients with coronary heart disease. Lancet 1994;344: 1383-9. - Mallinckrodt CH, Lane PW, Schnell D,
  4. [28]28. cardiovascular risk factor? Prog Cardiovasc Dis 2009;52:1-5. - Fox K, Ford I, Steg PG, Tendera M,
  5. [36]36. Califf RM. Clinical trial issues in weightloss therapy. Am Heart J 2006;151:633-42. Johansson K, Neovius K, DeSantis SM,

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Authors
James, W. P. T., Caterson, I. D., Coutinho, W., Finer, N., Van Gaal, L. F., Maggioni, A. P., Torp-Pedersen, C., Sharma, A. M., Shepherd, G. M., Rode, R. A., & Renz, C. L.
Affiliations
  • London School of Hygiene & Tropical Medicine (GB)
  • The University of Sydney (AU)
  • Pontifícia Universidade Católica do Rio de Janeiro (BR)
  • University College London (GB)
  • Associazione Nazionale Medici Cardiologi Ospedalieri (IT)
  • Gentofte Hospital (DK)
  • University of Alberta (CA)
  • Abbott (United States) (US)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2010-09-02
Volume
363
Issue
10
Pages
905-917
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa1003114
OpenAlex
W2119779723
Cited by
943
References
33
Citations by year
2026: 27 · 2025: 43 · 2024: 50 · 2023: 40 · 2022: 35 · 2021: 50 · 2020: 45 · 2019: 36 · 2018: 54 · 2017: 38 · 2016: 63 · 2015: 69 · 2014: 75 · 2013: 91 · 2012: 93
FWCI
75.02
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • UCrea (University of Cantabria) (submittedVersion, cc-by)
  • UWA Profiles and Research Repository (UWA) (submittedVersion)
  • CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion, other-oa)
  • ORBi (University of Liège) (submittedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
  • Abbott Laboratories
  • Bristol-Myers Squibb
  • Eli Lilly and Company
  • Pfizer
  • AstraZeneca
  • GlaxoSmithKline
  • Sanofi
  • University of Cambridge
  • Eisai
  • Novo Nordisk
  • Shionogi
  • Servier
  • Allergan
Topics
  • Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
Keywords
sibutramine, cardiovascular outcomes, obesity, overweight, weight management, cardiovascular risk, myocardial infarction, stroke, cardiovascular mortality, type 2 diabetes, blood pressure, weight loss, older adults, drug safety, appetite suppressants, anti-obesity drugs, cardiovascular events, cardiovascular risk reduction, cardiovascular risk stratification
MeSH terms
Aged, Appetite Depressants, Blood Pressure, Cardiovascular Diseases, Cyclobutanes, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Humans, Male, Middle Aged, Myocardial Infarction, Obesity, Stroke, Overweight, Kaplan-Meier Estimate

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