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Zepbound ® (tirzepatide) injection
2.5 mg/ 5 mg/ 7.5 mg/ 10 mg/ 12.5 mg/ 15 mg
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
What was the effect of Zepbound® (tirzepatide) on people with moderate to severe sleep apnea and obesity?
Tirzepatide achieved a least squares mean (LSM) apnea-hypopnea index (AHI) reduction of 25.3 events/h in non-positive airway pressure (PAP) users, compared to 5.3 events/h with placebo; in PAP users, reductions were 29.3 vs. 5.5 events/h, respectively.
See important safety information, including boxed warning, in the attached prescribing information.
Content overview
SURMOUNT-OSA Clinical Trial
The SURMOUNT-OSA master protocol described two 52-week, phase 3, double-blind, randomized studies of tirzepatide maximum tolerated dose (MTD) (10 or 15 mg) once weekly compared with placebo in 469 adults with moderate to severe obstructive sleep apnea (OSA) and obesity.1
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Study Design
The two studies that comprised SURMOUNT-OSA randomized 469 study participants across the United States, Australia, Brazil, China, Czechia, Germany, Japan, Mexico, and Taiwan in a 1:1 ratio to receive tirzepatide MTD (10 or 15 mg) or placebo across (SURMOUNT-OSA ISA Master Protocol) 2 intervention-specific studies including
Figure 1 description: One master protocol supports 2 studies/intervention-specific appendix. The first study includes participants who are unwilling or unable to use PAP therapy and the second study includes participants on PAP therapy. Both were randomized 1:1 to receive either tirzepatide MTD (10 or 15 mg) or placebo for 52 weeks.
Abbreviations: ISA = intervention-specific appendix; MTD = maximum tolerated dose; PAP = positive airway pressure; QW = every week.
The primary outcome of both studies was to demonstrate that tirzepatide MTD (10 or 15 mg) is superior compared with placebo as adjunct to diet and exercise for mean decrease in AHI by week 52.1
AHI was measured via centrally scored overnight polysomnography studies. The American Academy of Sleep Medicine rule 1B for identification of hyponeas was used which specifies a ≥30% reduction in airflow for ≥10 seconds and oxygen desaturation of ≥4% from pre-event baseline.1,3
The study designs included a 52-week study period, of which up to 20 weeks was a dose escalation period. The starting dose of tirzepatide was 2.5 mg once weekly for 4 weeks, escalated in 2.5 mg increments every 4 weeks until the MTD (10 or 15 mg) was achieved (SURMOUNT-OSA Master Protocol Dose Escalation Design).1
Figure 2 description: The starting dose of tirzepatide was 2.5 mg once weekly for 4 weeks, escalated in 2.5 mg increments every 4 weeks until the MTD (10 or 15 mg) was achieved.
Abbreviations: MTD = maximum tolerated dose; OSA = obstructive sleep apnea; QW = every week.
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Key Inclusion and Exclusion Criteria
Inclusion criteria for these studies were
- age ≥18 years
- moderate to severe OSA (apnea-hypopnea index [AHI] of ≥15 events/h, confirmed on polysomnography [PSG] prior to randomization)
- body mass index (BMI) of ≥30 kg/m²; for Japan only BMI ≥27 kg/m2, and
- history of at least one self-reported unsuccessful dietary effort to lose weight.1
Exclusion criteria for these studies were
- history of type 1 or type 2 diabetes or a glycated hemoglobin (HbA1c) ≥6.5%
- history of pancreatitis
- estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2
- use of any weight loss medication in the 3 months prior to screening
- weight change >5 kg within 3 months prior to screening
- prior or planned surgical or endoscopic treatment for obesity
- obesity induced by other endocrinologic disorders or monogenetic or syndromic forms of obesity
- any previous or planned surgery for sleep apnea or major ear, nose, or throat surgery
- significant craniofacial abnormalities that may affect breathing
- diagnosis of Cheyne-Stokes respiration or central or mixed sleep apnea
- active device treatment of OSA other than PAP (positive airway pressure), and
- respiratory and neuromuscular disease that could interfere with the trial results.1
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Baseline Characteristics
Baseline demographics and clinical characteristics of randomized participants for the 2 studies are presented in SURMOUNT-OSA Baseline Demographics and Clinical Characteristics.1
Parametera |
Participants not on PAP Therapy (Study 1) |
Participants on PAP Therapy (Study 2) |
||
Tirzepatide MTD |
Placebo |
Tirzepatide MTD |
Placebo |
|
Age, years |
47.3 ± 11.0 |
48.4 ± 11.9 |
50.8 ± 10.7 |
52.7 ± 11.3 |
Female, n (%) |
36 (31.6) |
41 (34.2) |
33 (27.5) |
32 (27.8) |
Race, n (%) |
||||
American Indian or Alaska Native |
9 (7.9) |
9 (7.5) |
10 (8.3) |
9 (7.9) |
Asian |
23 (20.2) |
24 (20.0) |
17 (14.2) |
16 (14.0) |
Black or African American |
6 (5.3) |
7 (5.8) |
8 (6.7) |
3 (2.6) |
White |
74 (64.9) |
80 (66.7) |
85 (70.8) |
86 (75.4) |
Multiple |
2 (1.8) |
0 |
N/A |
N/A |
Hispanic or Latino, n (%) |
51 (44.7) |
47 (39.2) |
38 (31.7) |
38 (33.0) |
Body weight, kg |
116.7 ± 24.6 |
112.8 ± 22.6 |
115.8 ± 21.5 |
115.1 ± 22.7 |
BMI, kg/m2 |
39.7 ± 7.3 |
38.6 ± 6.7 |
38.6 ± 6.1 |
38.7 ± 6.0 |
BMI category, n (%)b |
||||
<35 |
33 (28.9) |
44 (36.7) |
33 (27.7) |
33 (28.9) |
≥35 to <40 |
39 (34.2) |
35 (29.2) |
47 (39.5) |
41 (36.0) |
≥40 |
42 (36.8) |
41 (34.2) |
39 (32.8) |
40 (35.1) |
Waist circumference, cm |
122.6 ± 16.6 |
119.8 ± 14.8 |
120.7 ± 13.1 |
121.0 ± 14.0 |
AHI, events/h |
52.9 ± 30.5 |
50.1 ± 31.5 |
46.1 ± 22.4 |
53.1 ± 30.2 |
OSA severity, n (%)c |
||||
No Apnea |
0 |
1 (0.8) |
N/A |
N/A |
Mild – 5≤ AHI <15 events/h |
1 (0.9) |
2 (1.7) |
0 |
2 (1.8) |
Moderate – AHI ≥15 events/h |
39 (34.2) |
43 (36.1) |
35 (29.4) |
37 (32.5) |
Severe – AHI ≥30 events/h |
74 (64.9) |
73 (61.3) |
84 (70.6) |
75 (65.8) |
Missing |
0 |
1 |
1 |
1 |
PROMIS sleep-related impairment T-Scored |
53.2 ± 7.5 |
54.3 ± 8.5 |
55.3 ± 8.4 |
55.0 ± 9.5 |
PROMIS sleep disturbance T-Scoree |
53.8 ± 6.0 |
53.5 ± 7.4 |
56.0 ± 7.6 |
55.7 ± 7.6 |
Epworth sleepiness scoref |
10.3 ± 5.3 |
10.8 ± 5.2 |
10.8 ± 4.6 |
9.5 ± 4.4 |
Sleep apnea-specific hypoxic burden, % min/hg |
153.6 (102.7) |
137.8 (104.1) |
132.2 (83.4) |
142.1 (112.5) |
hsCRP, mg/Lh |
3.5 (120.0) |
3.6 (124.6) |
3.0 (124.3) |
2.7 (127.5) |
Hypertension, n (%) |
84 (73.7) |
93 (77.5) |
91 (75.8) |
91 (79.1) |
Systolic BP, mm Hg |
128.4 (12.2) |
130.3 (10.7) |
130.5 (14.3) |
130.5 (12.8) |
Diastolic BP, mm Hg |
83.7 (8.9) |
84.0 (8.6) |
83.2 (8.2) |
80.5 (8.6) |
Dyslipidemia, n (%) |
91 (79.8) |
98 (81.7) |
100 (83.3) |
97 (84.3) |
Prediabetes, n (%) |
74 (64.9) |
78 (65.0) |
69 (57.5) |
64 (55.7) |
HbA1c, % |
5.69 ± 0.37 |
5.64 ± 0.35 |
5.62 ± 0.37 |
5.65 ± 0.44 |
Abbreviations: AHI = apnea-hypopnea index; BMI = body mass index; BP = blood pressure; HbA1c = glycated hemoglobin; hsCRP = high-sensitivity C-reactive protein; MTD = maximum tolerated dose (10 or 15 mg); N/A = not applicable; OSA = obstructive sleep apnea; PAP = positive airway pressure.
aData are mean ± standard deviation or n (%) and include all randomized participants unless otherwise stated.
bStudy 2 had 1 missing participant value for each study arm for BMI category.
cParticipants with AHI <15 events/h were enrolled in error and were discontinued from the study.
dThe PROMIS short form sleep-related Iimpairment 8a consists of 8 items each rated on a 5-point scale ranging from “not at all” to “very much.” Items have a recall period of “in the past 7 days.” Individual item scores were totaled to obtain a raw score which was then converted to a T-score (using response pattern scoring) with a mean of 50 and a SD of 10. Higher scores indicate more sleep-related impairment.
eThe PROMIS short form sleep disturbance 8b consists of 8 items each rated on a 5-point scale ranging from “not at all” to “very much,” “never” to “always,” or “very poor” to “very good.” Items have a recall period of “in the past 7 days.” Individual item scores were totaled to obtain a raw score which was then converted to a T-score (using response pattern scoring) with a mean of 50 and a SD of 10. Higher scores indicate more sleep disturbance.
fThe Epworth Sleepiness Scale (ESS) is an 8-item participant-completed measure that asks the participant to rate on a scale of 0 (would never doze) to 3 (high chance of dozing), their usual chances of dozing in 8 different daytime situations, with a recall period of “in recent times.” The ESS total score is the sum of the 8-item scores and ranges from 0 to 24, with higher scores indicating greater daytime sleepiness.
gA measure calculated from a polysomnography that encapsulates frequency, duration, and depth of respiratory-event-related oxygen desaturation.
hData are geometric mean (coefficient of variation, %).
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Efficacy Results
In study 1, tirzepatide achieved least squares mean (LSM) AHI reduction of 25.3 events/h compared with 5.3 events/h for placebo. In study 2, tirzepatide achieved AHI reduction of 29.3 events/h compared with 5.5 events/h for placebo. In both phase 3 studies tirzepatide met all primary and key secondary endpoints (Primary and Key Secondary Endpoints for SURMOUNT-OSA Master Protocol Studies at Week 52 for the Treatment-Regimen Estimand,).1
Parameterb |
Participants not on PAP Therapy (Study 1) |
Participants on PAP Therapy (Study 2) |
||||
Tirzepatide MTD |
Placebo |
ETD or RRc (95% CI); p value |
Tirzepatide MTD |
Placebo |
ETD or RRc (95% CI); p value |
|
Primary endpoint |
||||||
Change in AHI, events/h |
-25.3 (-29.3 to -21.2) |
-5.3 (-9.4 to -1.1) |
ETD -20.0 (-25.8 to -14.2); p<0.001 |
-29.3 (-33.2 to -25.4) |
-5.5 (-9.9 to -1.2) |
ETD -23.8 (-29.6 to -17.9); p<0.001 |
Key secondary endpoints |
||||||
Percent change in AHI, % |
-50.7 (-62.3 to -39.11) |
-3.0 (-16.9 to 10.9) |
ETD -47.7 (-65.8 to -29.6); p<0.001 |
-58.7 (-69.1 to -48.4) |
-2.5 (-16.2 to 11.2) |
ETD -56.2 (-73.7 to -38.7); p<0.001 |
Participants with AHI reduction of ≥50% |
70 (61.2%) |
23 (19.0%) |
RR 3.3 (2.1 to 5.1); p<0.001 |
86 (72.4%) |
27 (23.3%) |
RR 3.1 (2.1 to 4.5); p<0.001 |
Participants with AHI <5 or AHI 5-14 with Epworth sleepiness score ≤10, % |
48 (42.2%) |
19 (15.9%) |
RR 2.9 (1.8 to 4.8); p<0.001 |
60 (50.2%) |
16 (14.3%) |
RR 3.3 (2.0 to 5.4); p<0.001 |
Percent change in body weight, % |
-17.7 (-19.0 to -16.3) |
-1.6 (-2.9 to -0.2) |
ETD -16.1 (-18.0 to -14.2); p<0.001 |
-19.6 (-21.0 to -18.2) |
-2.3 (-3.8 to -0.9) |
ETD -17.3 (-19.3 to -15.3); p<0.001 |
Change in hsCRP, mg/dL |
-1.4 (-1.7 to -1.1) |
-0.7 (-1.1 to -0.3) |
ETD -0.7 (-1.2 to ‑0.2); p=0.004 |
-1.4 (-1.6 to -1.1) |
-0.3 (-0.8 to 0.1) |
ETD -1.0 (-1.6 to ‑0.5); p<0.001 |
Change in sleep apnea-specific hypoxic burden, % min/h |
-95.2 (-103.2 to -87.2) |
-25.1 (-44.3 to -5.9) |
ETD -70.1 (-90.9 to -49.3); p<0.001 |
-103.0 (-110.3 to -95.6) |
-41.7 (-63.9 to -19.5) |
ETD -61.3 (-84.7 to -37.9); p<0.001 |
Change in systolic BP at week 48,d mmHg |
-9.5 (-11.5 to -7.5) |
-1.8 (-3.9 to 0.2) |
ETD -7.6 (-10.5 to -4.8); p<0.001 |
-7.6 (-9.7 to -5.6) |
-3.9 (-6.3 to -1.6) |
ETD –3.7 (-6.8 to -0.7); p=0.017 |
Other secondary endpointse |
||||||
Change in diastolic BP at week 48,d mmHg |
-4.9 (-6.4 to -3.5) |
-2.1 (-3.6 to -0.6) |
ETD -2.8 (-5.0 to -0.7) |
-3.3 (-4.7 to -1.9) |
-2.2 (-3.8 to -0.6) |
ETD -1.1 (-3.2 to 1.0) |
Abbreviations: AHI = apnea-hypopnea index; BP = blood pressure; ETD = estimated treatment difference; hsCRP = high-sensitivity C-reactive protein; MTD = maximum tolerated dose (10 or 15 mg); OSA = obstructive sleep apnea; PAP = positive airway pressure; RR = relative risk.
aTreatment-regimen estimand represented the average treatment effect of tirzepatide relative to placebo for all participants who had received at least one dose of study treatment regardless of study treatment discontinuation for any reason.
bData are least-squares means (95% confidence interval) or n (%) using the treatment-regimen estimand, unless otherwise stated.
cRelative risks are calculated using g-computation methods from logistic regression. P-values for categorical endpoints are based on logistic regression model.
dBlood pressure data from baseline to week 48 to prevent PAP withdrawal in Study 2 from confounding the assessment.
eConfidence intervals for any endpoint that is not part of the primary or key secondary endpoints, have not been adjusted for multiplicity and should not be used to make inferences.
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Safety Results
Treatment discontinuation rates due to adverse events were
- 4.4% in the tirzepatide arm of Study 1
- 1.7% in the placebo arm of Study 1
- 3.3% in the tirzepatide arm of Study 2, and
- 7.0% in the placebo arm of Study 2.1
The adverse events reported in these studies were similar with those observed in other clinical studies with tirzepatide.1
There were no reported cases of medullary thyroid carcinoma.1
There were 2 adjudicated confirmed cases of acute pancreatitis in the tirzepatide arm of Study 2.1
There were 5 cases of severe or serious depressive disorder/suicidal ideation or behavior events across both studies (2 in tirzepatide arms and 3 in placebo arms).1
Parametera |
Participants not on PAP Therapy (Study 1) |
Participants on PAP Therapy (Study 2) |
||
Tirzepatide MTD |
Placebo |
Tirzepatide MTD |
Placebo |
|
Participants with ≥1 TEAE |
91 (79.8) |
92 (76.7) |
99 (83.2) |
83 (72.8) |
Serious AE |
9 (7.9) |
7 (5.8) |
7 (5.9) |
12 (10.5) |
Deaths |
0 |
0 |
0 |
0 |
Abbreviations: AE = adverse events; mITT = modified intent-to-treat; MTD = maximum tolerated dose (10 or 15 mg); OSA = obstructive sleep apnea; PAP = positive airway pressure; TEAE = treatment-emergent adverse event.
aData are number of participants (%) in the safety analysis set. Safety analysis set represents data obtained during treatment and safety follow-up period of set of participants from the mITT population, regardless of adherence to study intervention.
The most commonly reported adverse events in SURMOUNT-OSA master protocol studies were gastrointestinal-related and generally mild to moderate in severity, usually occurring during the dose escalation period.1
Parametera |
Participants not on PAP Therapy (Study 1) |
Participants on PAP Therapy (Study 2) |
||
Tirzepatide MTD |
Placebo |
Tirzepatide MTD |
Placebo |
|
Diarrhea |
30 (26.3) |
15 (12.5) |
26 (21.8) |
10 (8.8) |
Nausea |
29 (25.4) |
12 (10.0) |
26 (21.8) |
6 (5.3) |
Vomiting |
20 (17.5) |
5 (4.2) |
11 (9.2) |
1 (0.9) |
Constipation |
18 (15.8) |
3 (2.5) |
18 (15.1) |
5 (4.4) |
Eructation |
9 (7.9) |
0 (0.0) |
10 (8.4) |
1 (0.9) |
Gastroesophageal reflux disease |
9 (7.9) |
1 (0.8) |
6 (5.0) |
0 (0.0) |
Injection site reaction |
8 (7.0) |
1 (0.8) |
6 (5.0) |
0 (0.0) |
Abdominal pain |
7 (6.1) |
4 (3.3) |
5 (4.2) |
2 (1.8) |
Upper respiratory tract infection |
7 (6.1) |
10 (8.3) |
5 (4.2) |
8 (7.0) |
COVID-19 |
6 (5.3) |
10 (8.3) |
8 (6.7) |
11 (9.6) |
Nasopharyngitis |
3 (2.6) |
8 (6.7) |
15 (12.6) |
12 (10.5) |
Dyspepsia |
5 (4.4) |
2 (1.7) |
11 (9.2) |
1 (0.9) |
Gastroenteritis |
3 (2.6) |
4 (3.3) |
8 (6.7) |
1 (0.9) |
Upper Abdominal Pain |
4 (3.5) |
2 (1.7) |
7 (5.9) |
2 (1.8) |
Influenza |
4 (3.5) |
8 (6.7) |
3 (2.5) |
3 (2.6) |
Arthralgia |
3 (2.6) |
6 (5.0) |
4 (3.4) |
5 (4.4) |
Bronchitis |
0 (0.0) |
0 (0.0) |
3 (2.5) |
7 (6.1) |
Hypertension |
1 (0.9) |
8 (6.7) |
2 (1.7) |
2 (1.8) |
Abbreviations: COVID-19 = coronavirus disease 2019; MTD = maximum tolerated dose (10 or 15 mg); OSA = obstructive sleep apnea; PAP = positive airway pressure.
aData are n (%) and listed according to Medical Dictionary for Regulatory Activities, version 26.1, preferred terms.
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Discontinuation
The overall treatment discontinuation rates were
- 14.9% in the tirzepatide arm of Study 1
- 30.0% in the placebo arm of Study 1
- 10.0% in the tirzepatide arm of Study 2, and
- 26.1% in the placebo arm of Study 2.1
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Enclosed Prescribing Information
References
1Malhotra A, Grunstein RR, Fietze I, et al; SURMOUNT-OSA Investigators. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med. 2024;391(13):1193-1205. https://doi.org/10.1056/NEJMoa2404881
2Malhotra A, Bednarik J, Chakladar S, et al. Tirzepatide for the treatment of obstructive sleep apnea: rationale, design, and sample baseline characteristics of the SURMOUNT -OSA phase 3 trial. Contemp Clin Trials. 2024;141:107516. https://doi.org/10.1016/j.cct.2024.107516
3Berry R, Brooks R, Gamaldo C, et al. The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications, version 2.0.2. Darien, IL: American Academy of Sleep Medicine, 2012.
Date of Last Review: September 16, 2025