Tirzepatide for the treatment of obesity: Rationale and design of the <scp>SURMOUNT</scp> clinical development program

Roux, Carel W. le; Zhang, Shuyu; Aronne, Louis J.; Kushner, Robert F.; Chao, Ariana M.; Machineni, Sriram; Dunn, Julia P.; Chigutsa, Farai; Ahmad, Nadia; Bunck, Mathijs C.

doi:10.1002/oby.23612

Cited by 36 publications

(28 citation statements)

References 47 publications

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“…The clinical trial results from tirzepatide studies informs important information regarding its impact on glycemia, bodyweight and cardiometabolic parameters. The tirzepatide phase 3 program includes the SURPASS trials in people living with T2D and the SURMOUNT studies in individuals with obesity [32,33].…”

Section: Clinical Datamentioning

confidence: 99%

Glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor co-agonists for cardioprotection, type 2 diabetes and obesity: a review of mechanisms and clinical data

Goldenberg,

Teoh,

Verma

2023

Current Opinion in Cardiology

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Purpose of review Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are approved for the management of type 2 diabetes (T2D) and obesity, and some are recommended for cardiorenal risk reduction in T2D. To enhance the benefits with GLP-RA mono-agonist therapy, GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor co-agonists are in development to capitalize on the synergism of GLP-1 and GIP agonism. We review the mechanisms of action and clinical data for GLP-1/GIP receptor co-agonists in T2D and obesity and their potential role in cardiovascular protection. Recent findings Tirzepatide, a first-in-class unimolecular GLP-1/GIP receptor co-agonist, is approved for T2D and is awaiting approval for obesity management. Phase 3 trials in T2D cohorts revealed significant reductions in glycemia and body weight and superiority compared with GLP-1R mono-agonism with semaglutide. Tirzepatide has demonstrated significant body weight reductions in individuals with obesity but not diabetes. It enhances lipid metabolism, reduces blood pressure, and lowers liver fat content. Pooled phase 2/3 data showed cardiovascular safety in T2D while a post hoc analysis suggested tirzepatide slows the decline of kidney function in T2D. Summary GLP-1/GIP receptor co-agonists are a novel addition to the diabetes and obesity armamentarium. The cardiorenal-metabolic benefits position them as promising multiprong tools for metabolically complex individuals with chronic vascular complications.

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Section: Clinical Datamentioning

confidence: 99%

Glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor co-agonists for cardioprotection, type 2 diabetes and obesity: a review of mechanisms and clinical data

Goldenberg,

Teoh,

Verma

2023

Current Opinion in Cardiology

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“…The SURMOUNT clinical trials series is designed to evaluate the efficacy of once weekly subcutaneous tirzepatide for weight management in patients with or without diabetes. 20 The SURMOUNT-1 study, similar to STEP-1, included adult patients with (1) BMI ≥27 kg/m 2 with one or more weight-related condition or (2) BMI ≥30 kg/m 2 . Eligible patients had prior and unsuccessful weight loss attempts with dietary measures.…”

Section: Data Sourcementioning

confidence: 99%

“…Although the cost effectiveness of AOM has previously been shown, newer drugs have demonstrated efficacy for weight loss, including semaglutide and tirzepatide. [17][18][19][20] The cost-benefit analysis of using these medications is currently being explored by health care systems. This review describes clinical data and perspectives on pharmacoeconomic considerations for 2 incretin-based drugs used to promote weight loss, semaglutide and tirzepatide.…”

Section: Pharmacoeconomic Burden Of Obesitymentioning

confidence: 99%

“…21,22 Semaglutide works as a GLP-1 analog, and tirzepatide works as a dual GLP-1 and GIP analog. 21,22 Both drugs have demonstrated clear benefits in the setting of obesity management as summarized in the STEP-1 and SURMOUNT-1 trials 17,19,20 (Table 2).…”

Section: Clinical Efficacy: Semaglutide Versus Tirzepatidementioning

confidence: 99%

“…The SURMOUNT clinical trials series is designed to evaluate the efficacy of once weekly subcutaneous tirzepatide for weight management in patients with or without diabetes. 20 The SURMOUNT-1 study, similar to STEP- 2). 19 In April 2023, Eli Lilly and Company shared the results of the SURMOUNT-2 trial, which evaluated the efficacy and safety of tirzepatide 10 mg and 15 mg to placebo.…”

Section: Surmount Studies (Tirzepatide)mentioning

confidence: 99%

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Evaluating the Efficacy and Pharmacoeconomics of Semaglutide and Tirzepatide in the Setting of Obesity

Nguyen¹,

Wong²,

Cope³

2023

American Journal of Therapeutics

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Background: Obesity is a major and growing public health concern. The associated cost for obesity and its related comorbidities is approximately 30% of US health care expenditures annually. As additional pharmacotherapeutic options join the market to combat obesity, it is important to understand the financial impact it may have on overall health care costs. This article explores the efficacy and pharmacoeconomics of incretin mimetics, semaglutide and tirzepatide, in the setting of obesity. Area of Uncertainty: The cost of incretin mimetics (semaglutide and tirzepatide) and its overall impact on obesity management within the health care arena is being explored. The cost comparison of these medications is to be determined; however, it may represent an added cost to the total US health care expenditures. Data Sources: A PubMed and Google Scholar search was conducted using various search terms (eg, semaglutide, tirzepatide, pharmacoeconomics, and obesity). Therapeutic Advances: Based on the data reviewed, both semaglutide and tirzepatide are effective medication options for obesity management. Obesity-related management expenditures exceed $173 billion for the US health care system annually. The cost needed to treat for 1% of weight loss with semaglutide and tirzepatide was reported as $1845 and $985, respectively. More than 40% of adults (60 years or older) experience obesity. If 1%, 5%, or 10% of this population is treated with semaglutide, the annual Medicare costs will translate to excess of $2.6 billion, $13.3 billion, and $26.8 billion, respectively. Tirzepatide is not yet approved in the United States for obesity and its financial impact remains to be seen. Conclusions: Obesity is associated with burdensome health complications and costs. Semaglutide and tirzepatide are effective drug options for the management of obesity. The cost of these medications will no doubt present a challenge to the total health care expenditures, although the cost–benefit ratio may ultimately be favorable.

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Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity

Aronne,

Sattar,

Horn

et al. 2024

JAMA

106

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ImportanceThe effect of continued treatment with tirzepatide on maintaining initial weight reduction is unknown.ObjectiveTo assess the effect of tirzepatide, with diet and physical activity, on the maintenance of weight reduction.Design, Setting, and ParticipantsThis 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.InterventionsParticipants (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 MeasuresThe 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.ResultsParticipants (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 &lt; .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 &lt; .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 RelevanceIn participants with obesity or overweight, withdrawing tirzepatide led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction.Trial RegistrationClinicalTrials.gov Identifier: NCT04660643

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Tirzepatide for the treatment of obesity: Rationale and design of the SURMOUNT clinical development program

Cited by 36 publications

References 47 publications

Glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor co-agonists for cardioprotection, type 2 diabetes and obesity: a review of mechanisms and clinical data

Glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor co-agonists for cardioprotection, type 2 diabetes and obesity: a review of mechanisms and clinical data

Evaluating the Efficacy and Pharmacoeconomics of Semaglutide and Tirzepatide in the Setting of Obesity

Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity

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