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Cited by 66Pharmacology and Obesity TreatmentBariatric Surgery and OutcomesObesity and Health Practices

Effectiveness and safety of drugs for obesity

Open access
Henderson Lewis, Kristina, Sloan, Caroline E, Bessesen, Daniel H, Arterburn, David·2024·BMJ
DOI 10.1136/bmj-2022-072686
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Abstract

Recent publicity around the use of new antiobesity medications (AOMs) has focused the attention of patients and healthcare providers on the role of pharmacotherapy in the treatment of obesity. Newer drug treatments have shown greater efficacy and safety compared with older drug treatments, yet access to these drug treatments is limited by providers' discomfort in prescribing, bias, and stigma around obesity, as well as by the lack of insurance coverage. Now more than ever, healthcare providers must be able to discuss the risks and benefits of the full range of antiobesity medications available to patients, and to incorporate both guideline based advice and emerging real world clinical evidence into daily clinical practice. The tremendous variability in response to antiobesity medications means that clinicians need to use a flexible approach that takes advantage of specific features of the antiobesity medication selected to provide the best option for individual patients. Future research is needed on how best to use available drug treatments in real world practice settings, the potential role of combination therapies, and the cost effectiveness of antiobesity medications. Several new drug treatments are being evaluated in ongoing clinical trials, suggesting that the future for pharmacotherapy of obesity is bright.

Integrity signals

Registry

Crossref · 10.1136/bmj-2022-072686

Cites

179 of 179 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

62 of 129 cited sources checked · 30 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Implicit and explicit bias against people with obesity is widespread among physicians, nurses, students, and nutritionists.

    “Implicit and explicit bias against people with obesity is widespread among physicians, nurses, students, and nutritionists,”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [62] source
    • cites [63] source

      The General Discussion (page unavailable) identifies obesity as a commonly endorsed stigmatized status, but that describes participants’ statuses, not bias among healthcare professionals. Searches for implicit and explicit obesity bias and for physicians, nurses, students, and nutritionists found no passage assessing its prevalence in those groups. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [64] source

      The ‘Impact on providers’ section says primary care providers, medical trainees, nurses and other healthcare professionals hold both explicit and implicit negative opinions about people with obesity. It does not identify practicing nutritionists specifically; its References list a study of weight bias among dietetics students, which does not establish the claim about nutritionists or both forms of bias in that group. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
  • Premisecitation

    In real-world effectiveness studies of currently approved antiobesity medications, most adverse events are reported as mild and moderate.

    “In real world effectiveness studies of currently approved antiobesity medications, most adverse events are reported as mild and moderate.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
  • Premisecitation

    Lisdexamfetamine is associated with modest weight loss.

    “Lisdexamfetamine is an amphetamine derivative, FDA approved for binge eating disorder and attention deficit hyperactivity disorder, and is associated with modest weight loss.”
    Quote in the paperSubstantial claim1 of 1 sources checked
  • Premisecitation

    Obesity is a relapsing, remitting chronic disease.

    “In light of the burden obesity places on human health and a growing understanding of the physiologic processes underlying weight regulation, scientific organizations including the American Medical Association, the National Institutes of Health, and others now recognize it as a relapsing, remitting chronic disease.”
    Quote in the paperSubstantial claim3 of 4 sources checked
    • cites [8] source

      The Position Statement (p. 7–9) calls obesity a chronic disease, and the Overview says multiple organizations have issued statements recognizing it as a disease. Our copy does not say that obesity is relapsing and remitting, or identify the American Medical Association and National Institutes of Health as endorsing that characterization. The References list a different statement describing obesity as ‘chronic relapsing progressive,’ not remitting. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [9] source
    • cites [10] source

      The Study Selection, Data Collection, and Analysis section explicitly calls obesity a chronic disease, and Limitations and Evidence Gaps describes physiological defenses against sustained weight loss. Neither passage characterizes obesity as relapsing and remitting or says that the American Medical Association and National Institutes of Health recognize it in those terms. Page numbers were not available in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [11] source

      The guideline’s “Medical management of the disease of obesity” section (p. 4) says scientific evidence supports viewing obesity as a disease, and “The challenge of weight reduction” (p. 4) describes biological responses that make weight regain likely. It does not characterize obesity as a “relapsing, remitting chronic disease” or say that the National Institutes of Health recognizes it as such. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
  • Premisecitation

    Clinical trials of antiobesity medications have provided strong evidence that clinically significant weight loss is maintained so long as patients stay on the drug treatment.

    “Increasingly, clinical trials of antiobesity medications follow patients up to 2-3 years after initiation of a drug treatment, and have provided strong evidence that clinically significant weight loss is maintained so long as patients stay on the drug treatment.38”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [38] source

      The Results (Weight loss) report clinically significant weight loss sustained through 108 weeks with phentermine/topiramate, including among participants still taking the study drug at week 108. This supports maintenance during a two-year trial, but this paper alone does not establish the claim across antiobesity medications, at three years, or for as long as treatment continues beyond the observed period. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • May combine two claims. 30
  • Classified as probably not a substantial claim. 35
  • The quote only partly states this claim. 12

  • May combine two claims.

    Interpretationcitation

    High cost of antiobesity medications, many of which are not covered by health insurance in the US, is likely to lead to uneven access and could further exacerbate obesity-related health disparities.

    “The high cost of these drug treatments, many of which are not covered by health insurance in the US, is likely to lead to uneven access to them, which could further exacerbate obesity related health disparities.”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    In surveys, physicians and advance practice providers describe major barriers to prescribing antiobesity medications, including high costs, lack of insurance coverage, side effects, medication interactions, insufficient knowledge, lack of time for weight loss counseling, and a perceived lack of efficacy.

    “In surveys, physicians and advance practice providers describe several major barriers to prescribing antiobesity medications, including high costs and lack of insurance coverage, side effects, medication interactions, insufficient knowledge, lack of time for weight loss counseling, and a perceived lack of efficacy.”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [57] source
    • cites [58] source

      The Underutilization section reports that physicians and health care providers cite concerns about safety and effectiveness, knowledge gaps, limited experience, inadequate insurance coverage, and high costs as reasons for not prescribing antiobesity drugs. It does not identify medication interactions or lack of counseling time as prescribing barriers, nor does it specifically report these findings for advanced practice providers. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [59] source

  • May combine two claims.

    Premisecitation

    Primary care physicians' knowledge of obesity guidelines is poor; in one survey of 1506 primary care physicians, only 8% could correctly identify guideline recommended weight and weight loss criteria for starting and continuing antiobesity medications.

    “Primary care physicians' knowledge of obesity guidelines is poor.In one survey of 1506 primary care physicians, only 8% could correctly identify guideline recommended weight and weight loss criteria for starting and continuing antiobesity medications”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [77] source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    The threshold for clinically significant response to antiobesity medication has traditionally been defined as 5% weight loss at three months after initiation.

    “The threshold for clinically significant response to antiobesity medication has traditionally been narrowly defined as 5% weight loss at three months after initiation 11”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A recent analysis of SURMOUNT-1 and STEP 1 trial data concluded that tirzepatide was likely more effective than semaglutide.

    “A recent analysis of SURMOUNT-1 and STEP 1 trial data concluded that tirzepatide was likely more effective than semaglutide.”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    Danuglipron is an oral small molecule GLP-1 receptor agonist undergoing phase 2 trials for obesity and type 2 diabetes.

    “Danuglipron is another oral small molecule GLP-1 receptor agonist that is undergoing phase 2 trials for the treatment of both obesity and type 2 diabetes.166”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Many drugs in the pipeline are based on incretin hormones, which have been found to be useful in the management of type 2 diabetes.

    “Many drugs in the pipeline are based on incretin hormones which have been found to be useful in the management of type 2 diabetes.163”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Phentermine-topiramate in addition to lifestyle modification was the most cost effective option, particularly when prescribed generically.

    “Finally, another model found that phentermine-topiramate in addition to lifestyle modification was the most cost effective option, particularly when prescribed generically.143”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [143] Atlas SJ, Beinfeld M, Lancaster V, et al. Medications for obesity management: effectiveness and value. Institute for Clinical and Economic Review. 2022. https://icer.org/wp-content/uploads/2022/03/ICER_Obesity_Evidence_Report_083122.pdf source

  • May combine two claims.

    Premisecitation

    In SURMOUNT 3, after 72 weeks, the placebo-subtracted weight loss in the 15 mg tirzepatide group was 19.9%, with a total placebo-subtracted weight loss including lifestyle intervention of 22.8%.

    “In SURMOUNT 3, subjects who lost >5% with an intensive lifestyle intervention were randomized to placebo, 10 mg, or 15 mg tirzepatide weekly.After 72 weeks, the placebo subtracted weight loss in the 15 mg group was 19.9%, with a total placebo subtracted weight loss including the lifestyle intervention of 22.8%.169”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [169] source

      The Results (Secondary outcomes; page unavailable) report placebo-subtracted total weight-loss differences, including the lifestyle intervention, of 19.9 percentage points for the treatment-regimen estimand and 22.8 for the efficacy estimand. Neither is a result for a separate 15 mg group: Methods (Randomization; page unavailable) says participants were assigned to placebo or a maximum tolerated tirzepatide dose of 10 or 15 mg. The claim incorrectly presents 19.9% as the 15 mg group's post-randomization result. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In the STEP 4 trial, after a 20-week run-in on semaglutide, those who remained on active drug lost an additional 8% of body weight, while those on placebo regained 7%, for a final difference of 15% body weight.

    “Following a 20 week run-in on semaglutide, the STEP 4 trial randomized participants to remain on study drug versus placebo until week 68.Those who remained on active drug lost an additional 8% of their body weight, while those on placebo regained 7%, for a final difference between groups of 15% body weight.156”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    At current prices in the US, the cost effectiveness of semaglutide or liraglutide in patients without type 2 diabetes exceeded commonly used cost effectiveness thresholds.

    “The model also reported that, at current prices in the US, the cost effectiveness of semaglutide or liraglutide in patients without type 2 diabetes exceeded commonly used cost effectiveness thresholds.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [143] Atlas SJ, Beinfeld M, Lancaster V, et al. Medications for obesity management: effectiveness and value. Institute for Clinical and Economic Review. 2022. https://icer.org/wp-content/uploads/2022/03/ICER_Obesity_Evidence_Report_083122.pdf source

  • May combine two claims.

    Premisecitation

    Phentermine was the most cost effective strategy among seven weight loss strategies plus no treatment over five years, followed by semaglutide, with all other treatment options dominated by these options.

    “Phentermine was found to be the most cost effective strategy, followed by semaglutide, with all other treatment options being dominated by these options (more effective and cheaper).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [142] source

      The Results (Base case results, page not provided) identify phentermine as the cost-effective strategy at five years and semaglutide as the most effective, but explicitly say semaglutide was not cost-effective because its ICER was prohibitively high. The One-way sensitivity results place both on the efficiency frontier, which helps explain the comparison, but does not support calling semaglutide the next most cost-effective strategy. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In 2013, The Obesity Society, the American Heart Association, and the American College of Cardiology issued a comprehensive obesity treatment guideline that was limited with respect to antiobesity medications.

    “In 2013, The Obesity Society, the American Heart Association, and the American College of Cardiology together issued a comprehensive obesity treatment guideline document.177 While expansive in detail on lifestyle interventions and bariatric surgery, this document was limited with respect to antiobesity medications.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [177] Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation 2014;129:S102-38. 01.cir.0000437739.71477.ee source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The 2013 guideline recommended considering discontinuation of antiobesity medications in patients not losing at least 5% of body weight after 12 weeks.

    “Additionally, it was recommended to consider discontinuation of antiobesity medications in patients not losing at least 5% of their body weight after 12 weeks of treatment.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [177] Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation 2014;129:S102-38. 01.cir.0000437739.71477.ee source

      Section 2.1 says the panel did not conduct a comprehensive assessment of pharmacotherapy, although it reviewed some evidence on orlistat. Searches for medication discontinuation, a 5% weight-loss threshold, and 12 weeks found no passage recommending the claimed stopping rule. (LLM, conf=0.75)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In 2015, the Endocrine Society released guidelines outlining the same initiation criteria as earlier guidelines, but also recommended continuation of antiobesity medications during weight loss maintenance and suggested a more detailed monitoring plan.

    “In 2015, following FDA approval of two new antiobesity medications for long term use, the Endocrine Society released its own guidelines outlining the same antiobesity medication initiation criteria as earlier guidelines, but also recommended continuation of antiobesity medications during weight loss maintenance, and suggested a more detailed plan for antiobesity medication monitoring.11”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    Most reviews on adult antiobesity medications from high profile groups are out of date and do not reflect the available evidence on the most recent antiobesity medication options.

    “Most reviews on adult antiobesity medications from high profile groups are also out of date, and do not reflect the available evidence on the most recent antiobesity medication options.179 -182”
    Quote in the paperSubstantial claim3 of 4 sources checked
    • cites [179] Padwal, 2004, Long-term pharmacotherapy for obesity and overweight, Cochrane Database Syst Rev source

      The Methods (page unavailable) show that this review's searches ended in December 2006, and the Background (page unavailable) identifies the three drugs it assessed: orlistat, sibutramine and rimonabant. This establishes the review's dated scope, but the paper does not assess whether most reviews from high-profile groups were out of date or whether they omitted evidence on the most recent medication options. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [180] source

      The Discussion (page unavailable) identifies this as a review of weight-loss drugs in adults with type 2 diabetes, chiefly fluoxetine, orlistat and sibutramine. It can serve as an example of an older review, but our copy does not establish that most reviews from high-profile groups are out of date or assess whether they reflect evidence on the most recent medication options. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [181] Siebenhofer, 2021, Long-term effects of weight-reducing drugs in people with hypertension, Cochrane Database Syst Rev source
    • cites [182] source

      The Data Sources and Searches section (page unavailable) dates this review’s final surveillance to March 23, 2018, and Study Selection lists the medications it covered. That establishes it as an example of a review with a defined evidence cutoff, but the paper does not establish that most high-profile reviews are out of date or assess whether they omit evidence on the most recent medication options. (LLM, conf=0.77)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    The American Gastroenterological Association guidelines advise against the use of orlistat as an antiobesity medication.

    “Importantly, they advise against the use of orlistat as an antiobesity medication, given the modern available options that are superior and better tolerated.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [10] source

      The guideline’s recommendation table suggests against orlistat for adults with obesity or overweight with weight-related complications, and the Discussion describes this as a conditional recommendation. The Discussion attributes that decision to modest weight loss and bothersome adverse effects; it does not say the recommendation was made because modern alternatives are both superior and better tolerated. It also notes that some patients may reasonably choose orlistat. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In 2022, the American Gastroenterological Association published guidelines that are the first to make priority recommendations for antiobesity medication selection based on evidence from individual agent trials, explicitly recommending semaglutide 2.4 mg because of the magnitude of clinical benefit.

    “Finally, in 2022, the American Gastroenterological Association published the most recent guidelines on the pharmacotherapy of obesity.10 These guidelines are the first to make priority recommendations for antiobesity medication selection on the basis of available evidence from individual agent trials, explicitly recommending the use of semaglutide 2.4 mg because of the magnitude of clinical benefi”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [10] source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The American Gastroenterological Association guidelines allow for off-label long-term phentermine prescribing, while acknowledging low quality of evidence.

    “Like the Endocrine Society, the American Gastroenterological Association guidelines also allow for off-label long term phentermine prescribing, while acknowledging the low quality of evidence in this space.”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The 2013 guideline recommended that FDA approved antiobesity medications could be considered as adjunctive treatment for adult patients with BMI ≥30 or ≥27 with a weight-related comorbidity who were unable to lose weight or sustain weight loss with lifestyle intervention alone.

    “An expert recommendation was made for when to initiate antiobesity medications, stating that FDA approved antiobesity medications could be considered as adjunctive treatment for adult patients with body mass index ≥30 or ≥27 with a weight related comorbidity, who were unable to lose weight or sustain weight loss with lifestyle intervention alone.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [177] Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation 2014;129:S102-38. 01.cir.0000437739.71477.ee source

      Section 2.2 (page unavailable) says lifestyle intervention should be foundational to additional weight-management efforts, including medications, and describes parts of the algorithm as expert opinion. Section 3.5 (page unavailable) discusses adjunctive treatment when patients cannot achieve or maintain sufficient weight loss. The retrieved passages do not state the claimed BMI thresholds or a specific recommendation to consider FDA-approved antiobesity medications for those patients. (LLM, conf=0.79)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    A 48-week trial of bimagrumab in subjects with obesity and type 2 diabetes produced 6.5% overall weight loss, but with a small increase in lean mass.

    “A 48 week trial of bimagrumab treatment in subjects with obesity and type 2 diabetes produced 6.5% overall weight loss, but with a small increase in lean mass.176”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The Endocrine Society advised against off-label prescribing of drug treatments indicated for other purposes solely to achieve weight loss.

    “The Endocrine Society advised against off-label prescribing of drug treatments indicated for other purposes solely to achieve weight loss.”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The American Gastroenterological Association guidelines prioritize liraglutide 3.0 mg, followed by phentermine-topiramate, and then naltrexone-bupropion.

    “The American Gastroenterological Association guidelines next prioritize liraglutide 3.0 mg, followed by phentermine-topiramate, and then naltrexone-bupropion.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [10] source

      The Conditional Moderate recommendations list liraglutide 3.0 mg, phentermine-topiramate ER, and naltrexone-bupropion ER in that order, each as an option alongside lifestyle modifications. But the Limitations and Evidence Gaps section says clinicians have limited guidance for hierarchical decision-making; the list order does not establish the claimed priority ranking. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Semaglutide and tirzepatide are substantially more expensive than older antiobesity medications.

    “They are also substantially more expensive than older antiobesity medications.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Guidelines generally recommend against the off-label use of drug treatments not approved by the FDA exclusively for weight loss purposes.

    “As noted above, guidelines generally recommend against the off-label use of these drug treatments exclusively for weight loss purposes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Phentermine is contraindicated in patients with heart failure.

    “SGLT2 inhibitors could be particularly useful in patients with heart failure, for whom phentermine is contraindicated.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    Antiobesity medications approved in 2015 or later include highly effective drug treatments with mean weight loss 11-21% that primarily target incretin pathways.

    “This group of antiobesity medications, which includes those currently awaiting approval, contains highly effective drug treatments (mean weight loss 11-21%) that primarily target incretin pathways such as the GLP-1 receptor agonist semaglutide (approved for obesity in 2021), and the novel combination GLP-1 receptor agonist/glucose dependent insulinotropic polypeptide (GIP) receptor agonist tirzep”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Antiobesity medications are an evidence-based adjunct to lifestyle treatment.

    “Antiobesity medications approved by the Food and Drug Administration are an evidence based adjunct to lifestyle treatment.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given

    Newer antiobesity medications have greater efficacy and safety than older antiobesity medications.

    “Newer drug treatments have shown greater efficacy and safety compared with older drug treatments, yet access to these drug treatments is limited by providers' discomfort in prescribing, bias, and stigma around obesity, as well as by the lack of insurance coverage.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Long-term data to guide outcome comparisons of phentermine with newer antiobesity medications are almost completely lacking.

    “Having been available on the market for over half a century, phentermine is currently the most widely prescribed antiobesity medication in the US because of its low cost; however, long term data to guide outcome comparisons with newer antiobesity medications are almost completely lacking.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisereasoning

    Modern guidelines recommend a long-term treatment approach that can include antiobesity medications.

    “Accordingly, modern guidelines recommend a long term treatment approach, which can include the use of antiobesity medications (AOM).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Rates of antiobesity medication prescriptions tend to be specific to the clinician and the site of practice, with a subset of clinicians and certain sites prescribing a majority of antiobesity medications.

    “Rates of antiobesity medication prescriptions tend to be specific to the clinician and the site of practice, with a subset of clinicians and certain sites prescribing a majority of antiobesity medications.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites 19 20 56

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisenone given

    Setmelanotide is not approved for treatment of general obesity but is specifically useful in monogenic and syndromic obesity.

    “This agent is not approved for treatment of general obesity but is specifically useful in monogenic and syndromic obesity.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisereasoning

    Phentermine is currently the most widely prescribed antiobesity medication in the US because of its low cost.

    “Having been available on the market for over half a century, phentermine is currently the most widely prescribed antiobesity medication in the US because of its low cost; however, long term data to guide outcome comparisons with newer antiobesity medications are almost completely lacking.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Antiobesity medications vary in average effectiveness, cost, and side effect profile.

    “Antiobesity medications vary in average effectiveness, cost, and side effect profile.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Many insurance companies in the United States currently do not cover antiobesity medications.

    “Many insurance companies in the United States currently do not cover antiobesity medications, so out-of-pocket costs usually play a role in the selection of antiobesity medication.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Phentermine is only FDA approved for three months of use.

    “Of note, unlike newer antiobesity medications, phentermine is only FDA approved for three months of use, although recent guideline documents do provide guidance for longer term prescribing (as summarized later).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    A newer antiobesity medication is not always inherently better or more effective for a given patient than an older one.

    “Importantly, although an increased understanding of obesity physiology has recently led to the introduction of some highly effective antiobesity medications, a newer antiobesity medication is not always inherently better or more effective for a given patient than an older one.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Antiobesity medications can cause a variety of side effects.

    “Antiobesity medications can cause a variety of side effects.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Access to antiobesity medications is limited by providers' discomfort in prescribing, bias, stigma around obesity, and lack of insurance coverage.

    “Newer drug treatments have shown greater efficacy and safety compared with older drug treatments, yet access to these drug treatments is limited by providers' discomfort in prescribing, bias, and stigma around obesity, as well as by the lack of insurance coverage.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Antiobesity medications improve several markers of health, including blood pressure, lipid levels, and glycemic control.

    “Antiobesity medications improve several markers of health, including blood pressure, lipid levels, and glycemic control.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In a randomized trial of 756 adults, phentermine-topiramate 7.5 mg/46 mg (-8.5%) and 15 mg/92 mg (-9.2%) achieved greater weight loss versus placebo and their respective monotherapies at 28 weeks.

    “Another randomized trial including 756 adults found that the combination phentermine-topiramate 7.5 mg/46 mg (-8.5%) and 15 mg/92 mg (-9.2%) achieved greater weight loss versus placebo (P<0.0001) and their respective monotherapies (P<0.05) at 28 weeks.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [139] source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Long-term efficacy estimates in real-world settings could reflect a selection for patients who find the drug treatments useful and are able to acquire them consistently.

    “Long term efficacy estimates in real world settings could reflect a selection for those patients who find the drug treatments useful and are able to acquire them consistently.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In a network meta-analysis, placebo-subtracted percentage weight loss was highest with phentermine-topiramate (-7.97%; 95% CI -6.7 to -9.3) and GLP-1 receptor agonists (-5.8%; -5.2 to -6.3).

    “The main findings were that placebo subtracted percentage weight loss was highest with phentermine-topiramate (-7.97%; 95% confidence interval -6.7 to -9.3) and GLP-1 receptor agonists (-5.8%; -5.2 to -6.3).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] source

  • May combine two claims.

    Premisecitation

    SURMOUNT 1 found that tirzepatide 15 mg weekly produced a 17.8% placebo-subtracted weight loss at 72 weeks, with 56.7% achieving >20% weight loss.

    “SURMOUNT 1 tested tirzepatide at 5, 10, or 15 mg weekly for 72 weeks, and found that the 15 mg formulation produced a 17.8% placebo subtracted weight loss, and 56.7% achieved >20% weight loss.167”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [167] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Modern obesity treatment guidelines state that, while promising, off-label combination therapy is not recommended.

    “Given a lack of research on this topic, modern obesity treatment guidelines state that, while promising, off-label combination therapy is not recommended.153”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [153] source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    A consensus on weight loss targets has not yet emerged, other than an established minimum of 5% weight loss.

    “A consensus on weight loss targets has not yet emerged, other than an established minimum of 5% weight loss.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Premisecitation

    Orlistat results in 49.7% of patients achieving 5% weight loss at 12-24 months.

    “49.7 12”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] source

  • May combine two claims.

    Premisecitation

    In a more recent study in subjects with type 2 diabetes, the combination of cagrilintide and semaglutide produced a 15.6% weight loss at 32 weeks; the study had no placebo group.

    “In a more recent study in subjects with type 2 diabetes, this combination produced a 15.6% weight loss at 32 weeks.This study also had no placebo group.175”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [175] source

  • May combine two claims.

    Premisecitation

    Retatrutide administered at 1-12 mg weekly for 48 weeks produced a placebo-subtracted weight loss ranging from 6.6-22.1% in a phase 2 trial; 48% of participants on the highest dose lost >25% of baseline weight and 26% lost >30%.

    “Recent phase 2 trial data on retatrutide administered at doses of 1-12 mg weekly for 48 weeks showed a placebo subtracted weight loss ranging from 6.6-22.1%.173 In this study, 48% of participants on the highest dose lost >25% of baseline weight and 26% lost >30%.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [173] source

  • The quote only partly states this claim.

    Premisecitation

    Orlistat produces a placebo-subtracted weight loss of 3.2% (95% CI 2.8-3.5) at 12-24 months.

    “3.2 (95% CI 2.8-3.5) 12”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] source

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    The advent of newer, highly effective antiobesity medications has brought pharmacotherapy of obesity into the mainstream, and patients are increasingly asking their physicians for advice on these drug treatments.

    “However, the advent of newer, highly effective antiobesity medications has brought pharmacotherapy of obesity into the mainstream, and patients are increasingly asking their physicians for advice on these drug treatments.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The authors consulted patient experts from the Obesity Action Coalition, and four people with lived experience of obesity reviewed a draft manuscript and provided input.

    “The Obesity Action Coalition (OAC), a patient advocacy organization based in the United States, was contacted by the authors with a request for help in identifying people living with obesity who might be willing to provide input for this review.The four people listed in the contribution section were identified with the help of the OAC, and they reviewed a draft manuscript and provided input.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Very few new antiobesity agents are currently being tested in children and adolescents.

    “Unfortunately, very few of these new agents are currently being tested in children and adolescents.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    This perception has been reflected in the underuse of antiobesity medications by a minority of clinicians.

    “This perception has been reflected in the underuse of antiobesity medications by a minority of clinicians.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Prescription rates are increasing rapidly, leading to challenges in maintaining drug treatment supply.

    “Prescription rates are increasing rapidly, leading to challenges in maintaining drug treatment supply.183”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [183] Sumithran P, Finucane FM, Cohen RV. Obesity drug shortages are symptomatic of wider malaise. Lancet 2023;S0140-6736(23)01963-3. source

  • The quote only partly states this claim.

    Premisecitation

    Phentermine-topiramate ER produces a placebo-subtracted weight loss of 7.9% (95% CI 6.7-9.3) at 12-24 months.

    “7.9 (95% CI 6.7-9.3) 12”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] source

  • May combine two claims.

    Premisecitation

    The combination of cagrilintide 4.5 mg plus semaglutide 2.4 mg per week produced a 15.4% reduction in body weight at 20 weeks in patients with overweight or obesity; the study had no placebo arm.

    “In a study of patients with overweight or obesity, the combination of cagrilintide 4.5 mg plus semaglutide 2.4 mg per week produced a 15.4% reduction in body weight at 20 weeks.152 That study had no placebo arm, and participants were instructed not to change their diet or physical activity.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [152] source

  • May combine two claims.

    Premisecitation

    SAR441255 is a triple agonist currently in early human trials.

    “SAR441255 is another triple agonist currently in early human trials.174”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [174] source

  • The quote only partly states this claim.

    Premisecitation

    Naltrexone-bupropion SR produces a placebo-subtracted weight loss of 4.1% (95% CI 3.0-5.2) at 12-24 months.

    “4.1 12 (95% CI 3.0-5.2)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] source

  • The quote only partly states this claim.

    Premisecitation

    Liraglutide results in 64% of patients achieving 5% weight loss at 12-24 months.

    “64 12”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] source

  • The quote only partly states this claim.

    Premisecitation

    Metformin results in 43.2% of patients achieving 5% weight loss at 12-24 months.

    “43.2 12”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] source

  • The quote only partly states this claim.

    Premisecitation

    Liraglutide produces a placebo-subtracted weight loss of 4.7% (95% CI 4.1-5.3) at 12-24 months.

    “4.7 (95% CI 4.1-5.3) 12”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] source

  • The quote only partly states this claim.

    Premisecitation

    Topiramate results in 36-67% of patients achieving 5% weight loss.

    “36-67”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [49] source
    • cites [50] source

  • The quote only partly states this claim.

    Premisecitation

    Phentermine-topiramate ER results in 74.4% of patients achieving 5% weight loss at 12-24 months.

    “74.4 12”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] source

  • The quote only partly states this claim.

    Premisecitation

    Tirzepatide results in 85-91% of patients achieving 5% weight loss at 12-24 months depending on dose.

    “85-91 depending on dose”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] source

  • The quote only partly states this claim.

    Premisecitation

    Naltrexone-bupropion SR results in 64.6% of patients achieving 5% weight loss at 12-24 months.

    “64.6 12”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisecitation

    Bupropion results in 40% of patients achieving 5% weight loss.

    “40”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [51] source

  • The quote only partly states this claim.

    Premisecitation

    Tirzepatide produces a placebo-subtracted weight loss ranging from 11.9% (95% CI 10.4-13.4) to 17.8% (95% CI 16.3-19.3) at 12-24 months depending on dose.

    “11.9 (95% CI dose 10.4-13.4) to 17.8 43 (95% CI 16.3-19.3) depending on”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [43] source
69 of 69

  • The paper relies on this without support.

    Patient response to antiobesity medications is highly variable.

    “As is true with other forms of obesity treatment, patient response to antiobesity medications is highly variable.”

  • The paper relies on this without support.

    GLP-1 receptor agonists are particularly useful in people with type 2 diabetes.

    “GLP-1 receptor agonists are particularly useful in people with type 2 diabetes.”

  • The paper relies on this without support.

    Newer antiobesity medications reliably produce more weight loss than older drug treatments, but they cost substantially more.

    “Newer antiobesity medications reliably produce more weight loss than older drug treatments, but they cost substantially more.”

  • The paper relies on this without support.

    Obesity is a serious and growing public health problem in the US and around the world.

    “Obesity is a serious and growing public health problem in the US and around the world.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Four drugs are described as three dual agonists

    Minor

    The sentence says there are three GLP-1/glucagon dual agonists but names four: mazdutide, survodutide, pemvidutide, and cotadutide.

1 of 1

Cited works that were retracted

Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.

  • Cites a retracted work: 10.1016/s0140-6736(21)01640-8

    Info

    The cited work was retracted on 2024-04-04 (notice 10.1016/s0140-6736(24)00318-0), not before this paper was published (2024-03-25).

    Cited work 10.1016/s0140-6736(21)01640-8 · retracted 2024-04-04 · notice 10.1016/s0140-6736(24)00318-0 · this paper published 2024-03-25

1 of 1

Cites

1 retracted

Flagged first, then by citations

2 of the 181 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. Atlas SJ, Beinfeld M, Lancaster V, et al. Medications for obesity management: effectiveness and value. Institute for Clinical and Economic Review. 2022. https://icer.org/wp-content/uploads/2022/03/ICER_Obesity_Evidence_Report_083122.pdf
  2. 10.1056/NEJMp2300516 · DOI · Paper page
  3. 10.1056/NEJMoa2206038 · DOI · Paper page

Cited by

Sorted by citations

Related

Authors
Henderson Lewis, K., Sloan, C. E., Bessesen, D. H., & Arterburn, D.
Affiliations
  • Duke University (US)
  • University of Colorado Anschutz (US)
  • Kaiser Permanente Washington Health Research Institute (US)
ORCID
Venue
BMJ
Publisher
BMJ
Published
2024-03-25
Volume
384
Pages
e072686
ISSN
1756-1833 (ISSN-L)
DOI
10.1136/bmj-2022-072686
OpenAlex
W4393161955
Semantic Scholar
f6651681d167bb9b63d69ed61ccc33816bd0d684
Cited by
66
References
181
Citations by year
2026: 14 · 2025: 37 · 2024: 15
FWCI
4.12
Type
journal article
Language
en
Open access
Licence
www.bmj.com/company/legal-information/terms-conditions/legal-information/tdm-licencepolicy (tdm)
Locations
  • BMJ (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
  • Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
  • Health Sciences › Health Professions › Pharmacy › Obesity and Health Practices
Keywords
anti-obesity drugs, obesity pharmacotherapy, drug efficacy, drug safety, weight stigma, insurance coverage, real-world evidence, combination therapy, cost-effectiveness, weight loss
MeSH terms
Humans, Obesity, Anti-Obesity Agents

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-11.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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