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Table 1: Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity
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Design
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Phase 3, randomized withdrawal clinical trial with a 36-week, open-label lead-in period (N= 783) followed by a 52-week, double-blind, placebo-controlled period (N= 670)
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Objective
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To assess the effect of tirzepatide, with diet and physical activity, on the maintenance of weight reduction
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Study Groups
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Tirzepatide (n= 335)
Placebo (n= 335)
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Inclusion Criteria
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≥18 years old; body mass index (BMI) of ≥ 30; or BMI ≥ 27 with at least one weight-related condition (ie. hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease)
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Exclusion Criteria
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Patients with diabetes, a history or planned surgical treatment for obesity, and the use of weight loss medications within three months before enrollment
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Methods
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Participants (n= 783) in the open-label lead-in period received weekly subcutaneous tirzepatide (10 or 15 mg) for 36 weeks. At week 36, 670 participants were randomized 1:1 to either continue tirzepatide (n = 335) or switch to placebo (n= 335) for 52 weeks.
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Duration
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Trial: March 29, 2021 to May 18, 2023
Intervention: 88 weeks
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Outcome Measures
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Primary: mean percent change in weight from week 36 to week 88
Secondary: proportion of participants at week 88 who maintained at least 80% of the weight loss during the lead-in period
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Baseline Characteristics
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Week 0 of lead-in period
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Week 36
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Tirzepatide (N= 607)
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Tirzepatide (n= 335)
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Placebo (n= 335)
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Age, years
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48 (13%)
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49 (13%)
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48 (12%)
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Female
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473 (70.6%)
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236 (70.4%)
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237 (70.7%)
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Duration of obesity, years
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15.5 ± 11.8
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15.9 ± 12.1
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15.2 ± 11.4
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Race
- Asian
- Black
- White
- Native
- Multiple
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48 (7.2%)
75 (11.2%)
537 (80.1%)
2 (0.3%)
8 (1.2%)
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26 (7.8)
39 (11.6)
264 (78.8%)
1 (0.3%)
5 (1.5%)
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22 (6.6%)
36 (10.7%)
237 (81.5%)
1 (0.3%)
3 (0.9%)
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Body weight, kg
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107.3 ± 22.3
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84.6 ± 19.8
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85.8 ± 22.3
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BMI
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38.4 ± 6.6
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30.3 ± 6.0
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30.7 ± 6.8
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Waist circumference, cm
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115.2 ± 14.5
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96.8 ± 14.1
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98.2 ± 16.0
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Fasting glucose, mg/dL
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94.8 ± 10.9
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85.1 ± 7.4
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85.0 ± 7.8
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Results
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Least-squares mean (95% CI)
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Absolute difference (95% CI)
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p-Value
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Tirzepatide (n= 335)
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Placebo (n= 335)
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Change in body weight from week 36 to 88, %
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-5.5 (-6.8 to -4.2)
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14.0 (12.8 to 15.2)
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-19.4 (-21.2 to -17.7)
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<.001
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Patients maintaining ≥80% of weight lost from wk 36 to 88
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300 (89.5%)
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55 (16.6%)
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44.0 (24.9 to 77.5)
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<.001
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Abbreviations: CI= Confidence Interval
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Adverse Events
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Common Adverse Events: mild to moderate gastrointestinal events (nausea (35.5%), diarrhea, (21.1%), constipation (20.7%), and vomiting (16.3%)
Serious Adverse Events: 2.0% during the lead in period; 3.0% during the double-blind period, with similar percentages across treatment groups
Adverse Events that Led to Discontinuation: 7.0% of patients during lead-in treatment period mainly due to gastrointestinal events; during the double-blind period, 1.8% of participants in the tirzepatide group and 0.9% in placebo group
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Study Author Conclusions
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After achieving clinically meaningful weight reduction during a 36-week tirzepatide lead-in treatment period, adults with obesity or overweight who continued treatment with maximum tolerated dose tirzepatide for an additional 52 weeks demonstrated superior weight maintenance and continued weight reduction compared to those who switched to placebo.
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