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PURPOSE: Rising obesity and type 2 diabetes mellitus (T2DM) rates can be mitigated by various strategies, with a 10% total body weight loss (TBWL) threshold often required for T2DM remission. T2DM remission rates after bariatric surgery like Roux-en-Y gastric bypass (RYGB) are well established; endoscopic sleeve gastroplasty (ESG) is a less invasive option that averages 15% TBWL and allows for T2DM remission. This study explores the DiaRem (Diabetes Remission post-RYGB) score's ability to predict T2DM remission 1-year post-ESG. MATERIALS AND METHODS: We conducted a retrospective cohort study on 39 individuals with T2DM who underwent ESG. Age, utilization of diabetes medications, insulin administration, and hemoglobin A1c levels were used to calculate the DiaRem score. The area under the receiver operating characteristic curve (AUC) was employed to evaluate the discriminative ability of DiaRem in distinguishing diabetes remission. RESULTS: Among the 39 patients with a median hemoglobin A1c of 6.7, 12.8% required insulin, and 43.6% used diabetes medication. At 1-year post-ESG, 69.2% of patients experienced diabetes remission with a median %TWBL of 12.7. The DiaRem score's ability to detect diabetes resolution for ESG patients had a sensitivity of 100% and a specificity of 58.3%, at the optimal cutoff value of 10. The AUC was 0.779 (95% CI 0.546-0.959). CONCLUSION: Our study demonstrated the DiaRem score's predictive value for T2DM remission post-ESG, highlighting its utility in clinical decision-making for ESG-related outcomes. Further investigation is needed to identify alternative indicators that may enhance predictive accuracy, thus refining personalized decision-making for this patient group.
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Diabetes Mellitus Tipo 2 , Gastroplastia , Obesidade Mórbida , Indução de Remissão , Redução de Peso , Humanos , Diabetes Mellitus Tipo 2/terapia , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Adulto , Gastroplastia/métodos , Resultado do Tratamento , Hemoglobinas Glicadas/metabolismo , Hemoglobinas Glicadas/análise , Derivação GástricaRESUMO
Background: An international panel of obesity medicine experts from multiple professional organizations examined patterns of obesity care and current obesity treatment guidelines to identify areas requiring updating in response to emerging science and clinical evidence. Aims: The panel focused on multiple medical health and societal issues influencing effective treatment of obesity and identified several unmet needs in the definition, assessment, and care of obesity. Methods: The panel was held in Leesburg, Virginia in September 2019. Results: The panelists recommended addressing these unmet needs in obesity medicine through research, education, evaluation of delivery and payment of care, and updating clinical practice guidelines (CPG) to better reflect obesity's pathophysiological basis and heterogeneity, as well as the disease's health, sociocultural, and economic complications; effects on quality of life; need for standards for quantitative comparison of treatment benefits, risks, and costs; and the need to more effectively integrate obesity treatment guidelines into routine clinical practice and to facilitate more direct clinician participation to improve public understanding of obesity as a disease with a pathophysiological basis. The panel also recommended that professional organizations working to improve the care of people with obesity collaborate via a working group to develop an updated, patient-focused, comprehensive CPG establishing standards of care, addressing identified needs, and providing for routine, periodic review and updating. Conclusions: Unmet needs in the definition, assessment and treatment of obesity were identified and a blueprint to address these needs developed via a clinical practice guideline that can be utilized worldwide to respond to the increasing prevalence of obesity.
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Fármacos Antiobesidade , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Obesidade , Adulto , Humanos , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/uso terapêutico , Obesidade/tratamento farmacológico , Redução de Peso/efeitos dos fármacos , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon/efeitos adversos , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon/uso terapêuticoRESUMO
Importance: The effect of continued treatment with tirzepatide on maintaining initial weight reduction is unknown. Objective: To assess the effect of tirzepatide, with diet and physical activity, on the maintenance of weight reduction. Design, Setting, and Participants: This phase 3, randomized withdrawal clinical trial conducted at 70 sites in 4 countries with a 36-week, open-label tirzepatide lead-in period followed by a 52-week, double-blind, placebo-controlled period included adults with a body mass index greater than or equal to 30 or greater than or equal to 27 and a weight-related complication, excluding diabetes. Interventions: Participants (n = 783) enrolled in an open-label lead-in period received once-weekly subcutaneous maximum tolerated dose (10 or 15 mg) of tirzepatide for 36 weeks. At week 36, a total of 670 participants were randomized (1:1) to continue receiving tirzepatide (n = 335) or switch to placebo (n = 335) for 52 weeks. Main Outcomes and Measures: The primary end point was the mean percent change in weight from week 36 (randomization) to week 88. Key secondary end points included the proportion of participants at week 88 who maintained at least 80% of the weight loss during the lead-in period. Results: Participants (n = 670; mean age, 48 years; 473 [71%] women; mean weight, 107.3 kg) who completed the 36-week lead-in period experienced a mean weight reduction of 20.9%. The mean percent weight change from week 36 to week 88 was -5.5% with tirzepatide vs 14.0% with placebo (difference, -19.4% [95% CI, -21.2% to -17.7%]; P < .001). Overall, 300 participants (89.5%) receiving tirzepatide at 88 weeks maintained at least 80% of the weight loss during the lead-in period compared with 16.6% receiving placebo (P < .001). The overall mean weight reduction from week 0 to 88 was 25.3% for tirzepatide and 9.9% for placebo. The most common adverse events were mostly mild to moderate gastrointestinal events, which occurred more commonly with tirzepatide vs placebo. Conclusions and Relevance: In participants with obesity or overweight, withdrawing tirzepatide led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction. Trial Registration: ClinicalTrials.gov Identifier: NCT04660643.
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Fármacos Antiobesidade , Obesidade , Redução de Peso , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Duplo-Cego , Polipeptídeo Inibidor Gástrico/administração & dosagem , Polipeptídeo Inibidor Gástrico/efeitos adversos , Polipeptídeo Inibidor Gástrico/farmacologia , Polipeptídeo Inibidor Gástrico/uso terapêutico , Obesidade/tratamento farmacológico , Obesidade/complicações , Sobrepeso/complicações , Sobrepeso/tratamento farmacológico , Resultado do Tratamento , Redução de Peso/efeitos dos fármacos , Receptor do Peptídeo Semelhante ao Glucagon 2/administração & dosagem , Receptor do Peptídeo Semelhante ao Glucagon 2/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 2/uso terapêutico , Incretinas/administração & dosagem , Incretinas/efeitos adversos , Incretinas/farmacologia , Incretinas/uso terapêutico , Fármacos Antiobesidade/administração & dosagem , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Quimioterapia de Manutenção , Injeções Subcutâneas , Suspensão de TratamentoRESUMO
Obesity is a heterogeneous disease and there is wide patient-to-patient variability in response to all anti-obesity treatments including lifestyle modifications, anti-obesity medications (AOMs), devices, and bariatric surgery. To effectively treat obesity, practitioners must be knowledgeable about all of these treatment modalities including on-label and off-label AOMs. Care should be individualized to the patient taking into consideration their unique challenges with weight loss, their goals, the presence of comorbidities, medication contraindications, and drug-drug interactions. There is currently no way to know which AOM will be most effective for a patient without trial and error; therefore, prescribe AOMs in sequence and consider combination therapy for optimal results. This article reviews the efficacy, safety, prescribing information, and other considerations for all of the currently available AOMs.
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Fármacos Antiobesidade , Cirurgia Bariátrica , Humanos , Fármacos Antiobesidade/uso terapêutico , Terapia Combinada , Obesidade/tratamento farmacológico , Obesidade/cirurgia , Resultado do TratamentoRESUMO
Several medications can contribute to weight gain. Medication-induced weight gain can have severe health consequences leading to overweight or obesity, or exacerbation of preexisting obesity and the plethora of obesity-related comorbidities. Weight gain due to medications is potentially avoidable by prescribing medications that are either weight neutral or that lead to weight loss, when appropriate. This article reviews the common classes of medications that contribute to weight gain and discusses alternatives to consider.
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Obesidade , Aumento de Peso , Humanos , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Redução de Peso , Doença IatrogênicaRESUMO
(1) Background: Prior research in individuals with overweight/obesity and prediabetes or type 2 diabetes has shown that the ingestion of protein-rich food and non-starchy vegetables before concentrated carbohydrates (a carbohydrate-last food order) led to lower postprandial glucose excursions over 180 min, compared to eating the same foods in the reverse order. To expand upon this research, we sought to examine the feasibility and impact of carbohydrate-last food order behavioral intervention on glucose tolerance (GT), HbA1c, weight, and nutrient intake in adults with prediabetes in the real world over a 16-week span. (2) Methods: A total of 45 adults with overweight/obesity and prediabetes were randomized to receive 4-monthly standard nutritional counseling (C) or standard nutritional counseling plus carbohydrate-last food order counseling (FO) sessions (NCT# NCT03896360). (3) Results: The FO group decreased in body weight (-3.6 ± 5.7 lbs, p = 0.017), and trended toward lower HbA1c (-0.1 ± 0.2, p = 0.054). The C group weight trended lower (-2.6 ± 6.8 lbs, p = 0.102) without altering HbA1c (-0.03 ± 0.3, p = 0.605). GT was unchanged in both groups after 16 weeks. Changes in weight, HbA1c, and GT were similar between groups. Sensitivity analysis of pre-COVID participants showed significant weight loss in the FO group (-5.9 ± 5.3 lbs, p = 0.003) but not in C group (-1.0 ± 6.8 lbs, p = 0.608). After 16 weeks, the C group significantly reduced its daily intake of calories, fat, protein, and grains whereas the FO group increased its daily intake of vegetables and protein. There were 17 (94%) FO participants that reported high intervention adherence and 13 (72%) reported it was easy to eat protein/vegetables before carbohydrates. (4) Conclusions: A carbohydrate-last food order is a feasible behavioral strategy in individuals with prediabetes that improves diet quality, notably increasing protein and vegetable intake.
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Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Adulto , Humanos , Estado Pré-Diabético/terapia , Hemoglobinas Glicadas , Sobrepeso/terapia , Projetos Piloto , Obesidade/terapia , Verduras , GlucoseRESUMO
Obesity is a chronic, progressive and relapsing disease with a rising global prevalence associated with increased morbidity and mortality and reduced quality of life. Treatment of obesity requires a comprehensive medical approach that includes behavioural interventions, pharmacotherapy and bariatric surgery. The degree of weight loss with all approaches is highly heterogeneous, and long-term weight maintenance remains challenging. For years, antiobesity medications have been limited in number, often delivering meagre efficacy and raising numerous safety concerns. Therefore, there is a need for the development of highly efficacious and safe new agents. Recent insights into the complex pathophysiology of obesity have increased our understanding of intervenable targets for pharmacotherapies to treat obesity and improve weight-related cardiometabolic complications, namely, type 2 diabetes, hyperlipidaemia and hypertension. As a result, novel potent therapies have emerged, such as semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) recently approved for the treatment of obesity. Semaglutide 2.4 mg once weekly significantly reduces body weight by approximately 15%, with simultaneous improvement in cardiometabolic risk factors and physical functioning in people with obesity. Tirzepatide, the first dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1RA, has recently demonstrated that body weight reduction exceeding 20% in people with obesity and coupled with improved cardiometabolic measures is feasible. Thus, these novel agents promise to narrow the gap between the weight-loss effects of behaviour interventions, previous pharmacotherapies, and bariatric surgery. In this narrative review, we highlight established and emerging therapeutic treatments for long-term obesity management and position them in a framework according to their weight loss effects.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Qualidade de Vida , Obesidade/complicações , Obesidade/terapia , Obesidade/induzido quimicamente , Polipeptídeo Inibidor Gástrico/uso terapêutico , Redução de Peso , Doenças Cardiovasculares/induzido quimicamente , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêuticoRESUMO
CONTEXT: Long-term treatment of obesity with lifestyle changes alone is unsustainable for most individuals because of several factors including adherence and metabolic adaptation. Medical management of obesity has proven efficacy for up to 3 years in randomized controlled trials. However, there is a dearth of information regarding real-world outcomes beyond 3 years. OBJECTIVE: This work aimed to assess long-term weight loss outcomes over a 2.5- to 5.5-year period with US Food and Drug Administration (FDA)-approved and off-label antiobesity medications (AOMs). METHODS: A cohort of 428 patients with overweight or obesity were treated with AOMs at an academic weight management center with an initial visit between April 1, 2014, and April 1, 2016. Intervention included FDA-approved and off-label AOMs. The primary outcome was percentage weight loss from initial to final visit. Key secondary outcomes included weight reduction targets as well as demographic and clinical predictors of long-term weight loss. RESULTS: The average weight loss was 10.4% at a mean follow-up duration of 4.4 years. The proportions of patients who met the weight reduction targets of 5% or greater, 10% or greater, 15% or greater, and 20% or greater were 70.8%, 48.1%, 29.9%, and 17.1%, respectively. On average, 51% of maximum weight loss was regained, while 40.2% of patients maintained their weight loss. In a multivariable regression analysis, a higher number of clinic visits was associated with more weight loss. Metformin, topiramate, and bupropion were associated with increased odds of maintaining 10% or greater weight loss. CONCLUSION: Clinically significant long-term weight loss of 10% or more beyond 4 years is achievable in clinical practice settings with obesity pharmacotherapy.
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Fármacos Antiobesidade , Obesidade , Humanos , Obesidade/tratamento farmacológico , Fármacos Antiobesidade/uso terapêutico , Topiramato/uso terapêutico , Redução de Peso , Estilo de VidaRESUMO
OBJECTIVE: Obesity is a growing global concern compounded by limited availability of effective treatment options. The SURMOUNT development program aims to evaluate the efficacy and safety of tirzepatide as an adjunct to lifestyle intervention compared with placebo on chronic weight management in adults with BMI ≥ 27 kg/m2 with or without type 2 diabetes. METHODS: The SURMOUNT program includes four global phase 3 trials NCT04184622 (SURMOUNT-1), NCT04657003 (SURMOUNT-2), NCT04657016 (SURMOUNT-3), and NCT04660643 (SURMOUNT-4). Participants are randomized to once-weekly subcutaneous tirzepatide versus placebo in a double-blind manner. The primary end point in all trials is the percentage change in body weight from randomization to end of treatment. Results for the primary end point for SURMOUNT-1 were published recently and results for the other trials are expected in 2023. RESULTS: Across trials, participants have a mean age of 44.9 to 54.2 years, are mostly female (50.7% to 69.7%), and have a mean BMI of 36.1 to 38.9. CONCLUSIONS: The extensive assessment of once-weekly tirzepatide in the global SURMOUNT program will detail the clinical effects of this first-in-class glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist in chronic weight management.
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Polipeptídeo Inibidor Gástrico , Obesidade , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glicemia , Diabetes Mellitus Tipo 2/complicações , Polipeptídeo Inibidor Gástrico/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Obesidade/tratamento farmacológicoRESUMO
BACKGROUND: We conducted this study to compare the weight loss outcome of intragastric balloons (IGBs) in conjunction with pharmacotherapy vs IGB and intensive lifestyle changes alone. METHODS: This was a multicenter, non-randomized, retrospective study involving 4 academic hospitals. Patients underwent IGB placement with or without concomitant anti-obesity pharmacotherapy. The primary outcome was percent total weight loss (TBWL) after IGB placement at 6 and 12 months. RESULTS: This study included 102 patients, with 23 patients (mean age 46.6 years, 82.6% female) treated with IGB/pharmacotherapy and 79 patients (mean age 46.0 years, 88.6% female) treated with IGB/lifestyle modifications. Patients had a 100% follow-up rate at 6 and 12 months. At 6 months following IGB placement, both groups achieved a similar %TBWL. At 12 months, %TBWL was greater in the IGB/pharmacotherapy group (12.6% ± 1.2 vs 9.7% ± 0.7, P = .04). 65.2% of patients achieved ≥10% TBWL at 12 months in the IGB/pharmacotherapy group, compared to 38.0% in the IGB/lifestyle group (P < .05). The proportion of patients that achieved ≥15% weight loss at 12 months was also significantly different between the IGB/pharmacotherapy and IGB/lifestyle groups (30.4% vs 20.3%, P < .05). DISCUSSION: IGB with concomitant use of pharmacotherapy did not improve weight loss while the IGB was in place compared to IGB and lifestyle changes. However, patients receiving IGB with pharmacotherapy did have greater weight loss and diminished weight regain after balloon removal compared to those receiving just IGB and lifestyle changes.
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Balão Gástrico , Obesidade Mórbida , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Balão Gástrico/efeitos adversos , Estudos Retrospectivos , Obesidade/complicações , Redução de Peso , Resultado do TratamentoRESUMO
Background: American adults have gained weight during the COVID-19 pandemic. Little is known about how patients who are medically managed for overweight and obesity, including patients who are prescribed antiobesity pharmacotherapy, have fared. Objective: To assess the COVID-19 pandemic's effect on weight, food choices, and health behaviors in patients receiving medical treatment for overweight or obesity. Methods: Adult patients treated at an urban academic weight management center between 1 May 2019 and 1 May 2020 were electronically surveyed between 23 February and 23 March 2021. The survey assessed changes in weight, eating, behaviors, and the use of antiobesity medications (AOMs) following issuance of social distancing/stay-at-home policies in March 2020. Results: In 970 respondents, median percent weight change for those taking AOMs was -0.459% [interquartile range -5.46%-(+3.73%)] compared to +2.33% [IQR -1.92%-(+6.52%)] for those not taking AOMs (p < 0.001). More participants achieved ≥5% weight loss if they were taking AOMs compared to those who were not (26.7% vs. 15.8%, p = 0.004), and weight gain ≥5% was also lower in those taking AOMs (19.8% vs. 30.3%, p = 0.004). Patients with pre-pandemic BMI ≥30 kg/m2 taking AOMs experienced the greatest weight reduction, and there was greater weight loss associated with increased physical activity. Conclusions and Relevance: Medical weight management protected against weight gain during this period of the COVID-19 pandemic. Increased physical activity, decreased alcohol intake, and use of AOMs were factors that contributed to this protective effect.
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OBJECTIVE: Recent changes to the Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (eGFR) formula (2021 CKD-EPI) removed race from the 2009 formula, increasing the number of Black people classified as having CKD, but these changes may impact eligibility and/or dosing for antiobesity medications. This study estimated the number of people with obesity nationwide who might have pharmacotherapy options impacted by the new formula. METHODS: Using National Health and Nutrition Examination Survey (NHANES) cohort study data, the number of people eligible for antiobesity medication was estimated, and the number who would require a dosage reduction or would no longer be eligible for specific medications based on the new eGFR formula was also estimated. RESULTS: Among 16,412,571 Black and 109,654,751 non-Black people eligible for antiobesity medication, 911,336 (6.1%) Black and 6,925,492 (6.6%) non-Black people had ≥CKD stage 3 by the 2009 CKD-EPI formula. Applying the 2021 CKD-EPI formula, 1,260,969 (8.5%) Black people and 4,989,919 (4.7%) non-Black people had ≥CKD stage 3. For medications requiring renal adjustment, the number of Black people who would require a lower dose or be precluded from using a medication increased by 24.7% to 50.2%. CONCLUSIONS: These findings highlight the importance of measuring-rather than estimating-GFR in Black people with CKD when considering many antiobesity pharmacotherapy options.
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Insuficiência Renal Crônica , Humanos , Taxa de Filtração Glomerular , Inquéritos Nutricionais , Estudos de Coortes , Insuficiência Renal Crônica/epidemiologia , Obesidade , CreatininaRESUMO
INTRODUCTION: Bariatric surgery is the most effective intervention currently available for significant and durable weight loss, but weight regain after surgery is not uncommon. This paper focuses on updates in behavioral interventions and pharmacotherapy to combat weight regain after bariatric surgery. AREAS COVERED: This paper critically reviews both prospective and retrospective studies assessing pharmacotherapy in post-bariatric surgical patients published within the past 5 years. It also evaluates updates in behavioral therapies and delivery of the therapies in this patient population. EXPERT OPINION: Weight regain after bariatric surgery is common. Patients who experience weight regain should be evaluated and treated by a multidisciplinary team. Antiobesity pharmacotherapy should be considered for those who qualify as an adjunct to lifestyle modifications, along with behavioral interventions such as cognitive behavioral therapy.
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Cirurgia Bariátrica , Obesidade Mórbida , Humanos , Obesidade Mórbida/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Aumento de PesoRESUMO
The obesity pandemic continues unabated despite a persistent public health campaign to decrease energy intake ("eat less") and increase energy expenditure ("move more"). One explanation for this failure is that the current approach, based on the notion of energy balance, has not been adequately embraced by the public. Another possibility is that this approach rests on an erroneous paradigm. A new formulation of the energy balance model (EBM), like prior versions, considers overeating (energy intake > expenditure) the primary cause of obesity, incorporating an emphasis on "complex endocrine, metabolic, and nervous system signals" that control food intake below conscious level. This model attributes rising obesity prevalence to inexpensive, convenient, energy-dense, "ultra-processed" foods high in fat and sugar. An alternative view, the carbohydrate-insulin model (CIM), proposes that hormonal responses to highly processed carbohydrates shift energy partitioning toward deposition in adipose tissue, leaving fewer calories available for the body's metabolic needs. Thus, increasing adiposity causes overeating to compensate for the sequestered calories. Here, we highlight robust contrasts in how the EBM and CIM view obesity pathophysiology and consider deficiencies in the EBM that impede paradigm testing and refinement. Rectifying these deficiencies should assume priority, as a constructive paradigm clash is needed to resolve long-standing scientific controversies and inform the design of new models to guide prevention and treatment. Nevertheless, public health action need not await resolution of this debate, as both models target processed carbohydrates as major drivers of obesity.
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Carboidratos da Dieta , Insulina , Carboidratos da Dieta/metabolismo , Ingestão de Energia/fisiologia , Metabolismo Energético/fisiologia , Humanos , Hiperfagia , Insulina/metabolismo , Obesidade/epidemiologiaRESUMO
BACKGROUND: Obesity is a chronic disease that results in substantial global morbidity and mortality. The efficacy and safety of tirzepatide, a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, in people with obesity are not known. METHODS: In this phase 3 double-blind, randomized, controlled trial, we assigned 2539 adults with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or more, or 27 or more and at least one weight-related complication, excluding diabetes, in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period. Coprimary end points were the percentage change in weight from baseline and a weight reduction of 5% or more. The treatment-regimen estimand assessed effects regardless of treatment discontinuation in the intention-to-treat population. RESULTS: At baseline, the mean body weight was 104.8 kg, the mean BMI was 38.0, and 94.5% of participants had a BMI of 30 or higher. The mean percentage change in weight at week 72 was -15.0% (95% confidence interval [CI], -15.9 to -14.2) with 5-mg weekly doses of tirzepatide, -19.5% (95% CI, -20.4 to -18.5) with 10-mg doses, and -20.9% (95% CI, -21.8 to -19.9) with 15-mg doses and -3.1% (95% CI, -4.3 to -1.9) with placebo (P<0.001 for all comparisons with placebo). The percentage of participants who had weight reduction of 5% or more was 85% (95% CI, 82 to 89), 89% (95% CI, 86 to 92), and 91% (95% CI, 88 to 94) with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and 35% (95% CI, 30 to 39) with placebo; 50% (95% CI, 46 to 54) and 57% (95% CI, 53 to 61) of participants in the 10-mg and 15-mg groups had a reduction in body weight of 20% or more, as compared with 3% (95% CI, 1 to 5) in the placebo group (P<0.001 for all comparisons with placebo). Improvements in all prespecified cardiometabolic measures were observed with tirzepatide. The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively. CONCLUSIONS: In this 72-week trial in participants with obesity, 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight. (Supported by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622.).