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Retatrutide-Obesity

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What is the impact of retatrutide in patients with obesity or overweight and obstructive sleep apnea?

In TRIUMPH-1-OSA and TRIUMPH-2-OSA, retatrutide 9 mg and 12 mg reduced the apnea-hypopnea index and body weight at Week 80 vs placebo in adults with moderate-to-severe obstructive sleep apnea and obesity or overweight.

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Content Overview

How were the TRIUMPH-1-OSA and TRIUMPH-2-OSA basket trials designed?
Which participants were eligible for TRIUMPH-1-OSA and TRIUMPH-2-OSA?
What was the efficacy of retatrutide in TRIUMPH-1-OSA and TRIUMPH-2-OSA?
- Primary and Key Secondary Endpoints
What was the safety profile of retatrutide in TRIUMPH-1-OSA and TRIUMPH-2-OSA?
What were the baseline characteristics of participants in TRIUMPH-1-OSA and TRIUMPH-2-OSA?
References

How were the TRIUMPH-1-OSA and TRIUMPH-2-OSA basket trials designed?

Molecule Description

Retatrutide is an investigational, once-weekly, triple agonist of the

glucose-dependent insulinotropic polypeptide (GIP) receptor
glucagon-like peptide-1 (GLP-1) receptor, and
glucagon receptor.^1,2

Trial Design and Treatment

The TRIUMPH-1 and TRIUMPH-2 clinical trials used a basket trial design that included powered and dedicated studies to evaluate the efficacy and safety of retatrutide in adults with obesity or overweight and obstructive sleep apnea (OSA) with and without type 2 diabetes (T2D). The OSA trials carried their own eligibility criteria, endpoints, and analyses while sharing the common TRIUMPH treatment design. TRIUMPH-1-OSA enrolled adults with moderate-to-severe OSA and obesity or overweight without T2D, and TRIUMPH-2-OSA enrolled adults with moderate-to-severe OSA and obesity or overweight with T2D.³

TRIUMPH-1-OSA and TRIUMPH-2-OSA were phase 3, multicenter, randomized, double-blind, placebo-controlled trials evaluating once-weekly subcutaneous retatrutide. TRIUMPH-1-OSA was conducted at 22 centers across 3 countries and randomized 243 participants, and TRIUMPH-2-OSA was conducted at 49 centers across 5 countries and randomized 448 participants.³

In each trial, participants were randomly assigned in a 1:1:1:1 ratio to

retatrutide 4 mg
retatrutide 9 mg
retatrutide 12 mg, or
placebo.³

Each trial comprised a 5-week screening period, an 80-week treatment period, and a 4-week posttreatment follow-up period, with the primary endpoint assessed at week 80.³

Retatrutide was initiated at 2 mg and escalated every 4 weeks until the randomly assigned dose was reached.³

All participants received individualized lifestyle counseling focused on a healthy, balanced diet combined with physical activity throughout the trial.³

Estimands and Statistical Analysis

For non-OSA-related endpoints, efficacy results were analyzed under 2 estimands

the efficacy estimand describes the treatment effect assuming that the intercurrent events of permanent discontinuation of study intervention and initiation of prohibited weight-management treatment did not occur, and
the treatment regimen estimand describes the treatment effect regardless of intercurrent events in all randomized participants on the basis of the treatment-policy strategy, consistent with the intention-to-treat analysis.³

For OSA-related endpoints, including the apnea-hypopnea index (AHI), sleep apnea-specific hypoxic burden (SASHB), and Patient-Reported Outcomes Measurement Information System (PROMIS) sleep scores, efficacy results were analyzed under 2 estimands

a hybrid-treatment regimen estimand used a hypothetical strategy for imputation of values related to intercurrent events associated with treatment failure and a treatment-policy strategy elsewhere, and
a hypothetical efficacy estimand to estimate a treatment effect on the assumption that all participants had received retatrutide or placebo for 80 weeks as intended by the protocol and did not have intercurrent events.³

Primary and key secondary endpoints were tested under a graphical multiplicity-control procedure, with a 2-sided significance level of .05 in TRIUMPH-1-OSA and .025 in TRIUMPH-2-OSA. The retatrutide 4-mg dose was not tested under this hierarchy for any endpoint, and any significance reported for that dose is nominal. Confidence intervals were not adjusted for multiplicity and should not be used for hypothesis testing.³

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Which participants were eligible for TRIUMPH-1-OSA and TRIUMPH-2-OSA?

Key inclusion and exclusion criteria for both trials are summarized in Table 1. Only key eligibility criteria are presented; the complete list of inclusion and exclusion criteria is available in the study protocols.³

**Table 1. Key Inclusion and Exclusion Criteria in TRIUMPH-1-OSA and TRIUMPH-2-OSA**³
TRIUMPH-1-OSA (Without T2D)		TRIUMPH-2-OSA (With T2D)
Inclusion Criteria	Exclusion Criteria	Inclusion Criteria	Exclusion Criteria
Adults aged ≥18 years without T2D BMI ≥30 kg/m² or ≥27 kg/m² with ≥1 weight-related comorbidity (hypertension, dyslipidemia, OSA, or CVD) At least 1 self-reported unsuccessful dietary effort to reduce body weight No weight change >5 kg (11 lb) in the 90 days before screening Previously diagnosed OSA with AHI ≥15 events/h on polysomnography at screening (≥4% oxygen desaturation threshold for hypopneas) Unable or unwilling to use PAP therapy for ≥4 weeks before screening, or receiving stable PAP therapy for ≥3 consecutive months and plan to continue PAP therapy during the study	Diagnosis of T1D or T2D Obesity due to endocrine, monogenetic, or syndromic causes Prior or planned bariatric surgery Renal impairment (eGFR <30 mL/min/1.73 m²), pancreatitis, hepatic disease, malignancy within 5 years, uncontrolled thyroid disease or elevated calcitonin, or personal or family history of MTC or MEN-2 Recent CV event (MI, stroke, revascularization, unstable angina, or CHF hospitalization within 90 days), or NYHA Class IV CHF Use of prescription or over-the-counter weight loss medications within 90 days of screening	Adults aged ≥18 years with T2D (HbA1c 6.5%-10.5% [48-91 mmol/mol]), receiving stable T2D treatment for ≥90 days BMI ≥27 kg/m² At least 1 self-reported unsuccessful dietary effort to reduce body weight No weight change > >5 kg (11 lb) in the 90 days before screening Previously diagnosed OSA with AHI ≥15 events/h on polysomnography at screening (≥4% oxygen desaturation threshold for hypopneas) Unable or unwilling to use PAP therapy for ≥4 weeks before screening, or receiving stable PAP therapy for ≥3 consecutive months and plan to continue PAP therapy during the study	Diagnosis of T1D Obesity due to endocrine, monogenetic, or syndromic causes Prior or planned bariatric surgery Renal impairment (eGFR <30 mL/min/1.73 m²), pancreatitis, hepatic disease, malignancy within 5 years, uncontrolled thyroid disease or elevated calcitonin, or personal or family history of MTC or MEN-2 Recent CV event (MI, stroke, revascularization, unstable angina, or CHF hospitalization within 90 days), or NYHA Class IV CHF Use of prescription or over-the-counter weight loss medications within 90 days of screening

Abbreviations: AHI = apnea-hypopnea index; BMI = body mass index; CHF = congestive heart failure; CV = cardiovascular; CVD = cardiovascular disease; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin; MEN-2 = multiple endocrine neoplasia syndrome type 2; MI = myocardial infarction; MTC = medullary thyroid carcinoma; NYHA = New York Heart Association; OSA = obstructive sleep apnea; PAP = positive airway pressure; T1D = type 1 diabetes; T2D = type 2 diabetes.
Notes: Only key eligibility criteria are shown.

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What was the efficacy of retatrutide in TRIUMPH-1-OSA and TRIUMPH-2-OSA?

Primary and Key Secondary Endpoints

In both trials, retatrutide 9-mg and 12-mg doses met the primary endpoint for the change in AHI from baseline to week 80 vs placebo (all p values <.001 in both estimands).³

Week 80 results for the primary and key secondary endpoints in both trials are presented in Table 2 under both the efficacy estimand and the treatment regimen estimand.³

**Table 2. Primary and Key Secondary Efficacy Endpoints at Week 80 in TRIUMPH-1-OSA and TRIUMPH-2-OSA**³
Endpoint^a	TRIUMPH-1-OSA				TRIUMPH-2-OSA
	RETA 4 mg (N=60)	RETA 9 mg (N=61)	RETA 12 mg (N=60)	PBO (N=62)	RETA 4 mg (N=116)	RETA 9 mg (N=109)	RETA 12 mg (N=110)	PBO (N=113)
Efficacy estimand
*Primary endpoint*
Change in AHI, events/h^b	-25.7^c	-36.1^d	-33.8^d	-11.1	-20.3^e	-26.6^d	-28.4^d	-10.6
*Key secondary endpoints*
Percent change in body weight	-14.0^d	-23.4^d	-23.0^d	-4.1	-12.7^f	-19.3^d	-19.9^d	-5.3
Percent change in AHI	-43.6^c	-60.6^d	-58.0^d	-15.9	-29.0^f	-43.0^d	-48.1^d	-15.0
Percent change in SASHB	-62.4^c	-78.8^d	-74.2^d	-25.8	-44.8^f	-64.6^d	-68.4^d	-28.9
Participants with a ≥50% decrease in AHI, %	53.6^c	68.2^d	65.9^d	23.1	40.5^f	56.1^d	58.1^d	24.6
Participants with AHI <5 events/h, or AHI 5-14 events/h with ESS score ≤10, %	32.1^c	54.3^d	45.5^d	10.4	24.6^f	44.2^d	42.3^d	13.1
Change in PROMIS-SRI T-score	-11.2	-13.4^c	-12.4^e	-7.9	-11.4	-12.0^c	-13.5^d	-7.4
Change in AHI in participants with BMI ≥35 kg/m², events/h^g	-26.4^e	-38.3^d	-36.7^d	-14.0	-21.9	-29.0	-31.4	-11.7
Percent change in body weight in participants with BMI ≥35 kg/m²^g	-13.5^d	-24.2^d	-22.8^d	-4.6	-13.0	-20.7	-20.7	-5.1
Treatment regimen estimand (hybrid-treatment regimen estimand for OSA-related endpoints)^h
*Primary endpoint*
Change in AHI, events/h^b	-22.9^e	-34.3^d	-31.7^d	-9.9	-19.2^e	-24.7^d	-25.4^d	-10.3
*Key secondary endpoints*
Percent change in body weight	-12.5^f	-22.2^d	-20.6^d	-4.8	-12.1^f	-17.9^d	-18.5^d	-5.6
Percent change in AHI	-38.5^f	-57.3^d	-53.3^d	-11.1	-27.6^f	-39.5^c	-40.9^d	-13.3
Percent change in SASHB	-56.4^f	-75.0^d	-70.2^d	-25.5	-43.9^f	-62.8^d	-64.1^d	-30.0
Participants with a ≥50% decrease in AHI, %	45.9^f	65.7^d	61.4^d	23.9	39.1^f	52.3^d	52.5^d	24.4
Participants with AHI <5 events/h, or AHI 5-14 events/h with ESS score ≤10, %	26.3^f	51.6^d	42.3^d	12.5	24.3^f	39.5^d	38.9^d	12.6
Change in PROMIS-SRI T-score	-10.5^g	-13.0^f	-12.2^f	-7.4	-10.9^g	-10.9^c	-12.6^d	-6.9
Change in AHI in participants with BMI ≥35 kg/m², events/h	-24.9^f	-36.8^d	-34.9^d	-13.6	-20.4^g	-25.6^g	-28.6^g	-11.6
Percent change in body weight in participants with BMI ≥35 kg/m²	-13.7^f	-23.6^d	-22.7^d	-6.1	-12.5^g	-18.6^g	-19.6^g	-5.4

Abbreviations: AHI = apnea-hypopnea index; BMI = body mass index; ESS = Epworth Sleepiness Scale; OSA = obstructive sleep apnea; PBO = placebo; PROMIS-SRI = Patient-Reported Outcomes Measurement Information System Sleep-Related Impairment; RETA = retatrutide; SASHB = sleep apnea-specific hypoxic burden.
Note: Confidence intervals were not adjusted for multiplicity and should not be used for hypothesis testing.
^a Data are model-based estimates at week 80 in all randomized participants.
^b The primary endpoint comparison was retatrutide 9 mg and 12 mg vs placebo; the retatrutide 4-mg comparison for change in AHI was a key secondary endpoint in both trials.
^c p<.01 vs placebo.
^d p<.001 vs placebo.
^e p<.05 vs placebo.
^f Gated outcome based on graphical testing scheme that did not pass family-wise error rate control.
^g These endpoints were key secondary endpoints in TRIUMPH-1-OSA and additional secondary endpoints in TRIUMPH-2-OSA; they were not included in the statistical testing hierarchy in TRIUMPH-2-OSA and no p values were reported for any dose in that trial.

^h For OSA-related endpoints (change in AHI, percent change in AHI, percent change in SASHB, the 2 responder endpoints, and PROMIS-SRI T-score), the treatment regimen estimand was applied as a hybrid-treatment regimen estimand, in which observed data following intercurrent events due to lack of efficacy were removed and imputed using a return-to-baseline approach. The body weight endpoints were analyzed under the treatment regimen estimand without hybrid imputation.

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What was the safety profile of retatrutide in TRIUMPH-1-OSA and TRIUMPH-2-OSA?

Adverse events (AEs) were reported by 88% to 93% of participants in the retatrutide groups and 76% in the placebo group in TRIUMPH-1-OSA and by 73% to 84% of participants in the retatrutide groups and 71%in the placebo group in TRIUMPH-2-OSA.³

These AEs were mostly gastrointestinal-related, generally mild to moderate in severity, and occurred most frequently during dose escalation. Discontinuation of treatment due to AEs occurred at similar frequencies in the retatrutide and placebo groups.³

An overview of AEs, treatment-emergent adverse events (TEAEs) occurring in ≥10% of participants in any treatment group, and other TEAEs of interest is presented in Table 3.³

**Table 3. Overview of Adverse Events and Treatment-Emergent Adverse Events in TRIUMPH-1-OSA and TRIUMPH-2-OSA, Safety Analysis Set**³
Adverse Event^a	TRIUMPH-1-OSA				TRIUMPH-2-OSA
Adverse Event^a	RETA 4 mg (N=60)	RETA 9 mg (N=61)	RETA 12 mg (N=60)	PBO (N=62)	RETA 4 mg (N=116)	RETA 9 mg (N=109)	RETA 12 mg (N=109)	PBO (N=112)
Overview of AEs, n (%)
Participants with ≥1 TEAE	56 (93)	56 (92)	53 (88)	47 (76)	85 (73)	86 (79)	92 (84)	80 (71)
Serious AEs	6 (10)	1 (2)	7 (12)	6 (10)	5 (4)	12 (11)	11 (10)	11 (10)
Death^b	0	0	0	2 (3)	0	1 (1)	0	1 (1)
AEs leading to study drug discontinuation	4 (7)	0	5 (8)	4 (6)	3 (3)	10 (9)	2 (2)	4 (4)
GI AEs leading to study drug discontinuation	1 (2)	0	4 (7)	1 (2)	0	1 (1)	1 (1)	0
TEAEs occurring in ≥10% of participants in any treatment group, n (%)
Diarrhea	18 (30)	27 (44)	21 (35)	9 (15)	29 (25)	40 (37)	38 (35)	11 (10)
Nausea	16 (27)	12 (20)	14 (23)	6 (10)	16 (14)	16 (15)	26 (24)	10 (9)
Constipation	12 (20)	10 (16)	14 (23)	6 (10)	22 (19)	12 (11)	24 (22)	9 (8)
Hyperglycemia	NR	NR	NR	NR	11 (9)	2 (2)	4 (4)	21 (19)
Dyspepsia	5 (8)	11 (18)	13 (22)	3 (5)	11 (9)	6 (6)	12 (11)	6 (5)
GERD	3 (5)	3 (5)	4 (7)	0	5 (4)	12 (11)	5 (5)	8 (7)
Influenza	6 (10)	6 (10)	7 (12)	9 (15)	6 (5)	4 (4)	7 (6)	7 (6)
Upper respiratory tract infection	9 (15)	7 (11)	3 (5)	3 (5)	8 (7)	2 (2)	6 (6)	4 (4)
Back pain	9 (15)	1 (2)	3 (5)	8 (13)	2 (2)	4 (4)	3 (3)	2 (2)
Headache	6 (10)	2 (3)	2 (3)	6 (10)	4 (3)	3 (3)	4 (4)	4 (4)
Urinary tract infection	7 (12)	1 (2)	3 (5)	4 (6)	5 (4)	4 (4)	11 (10)	5 (4)
Vomiting	5 (8)	3 (5)	6 (10)	1 (2)	5 (4)	7 (6)	12 (11)	3 (3)
Abdominal distension	4 (7)	4 (7)	6 (10)	0	4 (3)	9 (8)	6 (6)	2 (2)
Other TEAEs of special interest, n (%)
Adjudication-confirmed pancreatitis	0	0	1 (2)	0	0	0	0	0
Severe or serious arrhythmias and cardiac conduction disorders	0	0	1 (2)	1 (2)	0	1 (1)	0	0
Severe or serious GI AEs	0	0	3 (5)	1 (2)	0	3 (3)	2 (2)	1 (1)
Severe or serious acute renal events	0	0	0	0	0	1 (1)	1 (1)	0
Thyroid cancer and C-cell hyperplasia	0	0	0	0	1 (1)	0	0	0
Cancer	3 (5)	0	1 (2)	0	3 (3)	3 (3)	0	3 (3)
Severe or serious hepatic disorders	0	0	1 (2)	0	0	0	0	1 (1)
Severe or serious gallbladder and biliary tract disorders	1 (2)	0	1 (2)	0	0	1 (1)	0	0
Severe or serious potential nonimmediate hypersensitivity reactions	0	0	0	1 (2)	0	1 (1)	0	0
Injection site reactions	2 (3)	2 (3)	5 (8)	2 (3)	3 (3)	5 (5)	4 (4)	0
Severe or serious depression and suicidal ideation or behavior	0	0	0	0	0	0	0	0
Dysesthesia (skin burning sensation and related AEs)	1 (2)	8 (13)	5 (8)	1 (2)	5 (4)	5 (5)	8 (7)	0
Severe or serious malnutrition	0	0	0	0	0	0	0	0
Severe or serious ketoacidosis due to inadequate nutritional intake and other metabolic acidosis or ketosis	0	0	0	0	0	0	0	0
Adjudication-confirmed MACE^c	0	0	0	1 (2)	0	2 (2)	1 (1)	2 (2)

Abbreviations: AE = adverse event; GERD = gastroesophageal reflux disease; GI = gastrointestinal; MACE = major adverse cardiovascular event; NR = not reported, because the event did not meet the ≥10% reporting threshold in that trial; PBO = placebo; RETA = retatrutide; TEAE = treatment-emergent adverse event.
Notes: Participants might be counted in more than 1 category. Safety endpoints were analyzed with data from all the participants who underwent randomization and took at least 1 dose of retatrutide or placebo. Adverse events are listed according to Medical Dictionary for Regulatory Activities, version 28.1 for TRIUMPH-1-OSA and version 29.0 for TRIUMPH-2-OSA, preferred terms (PT) except for urinary tract infection which is reported by high-level term.

^a Data are presented as n (%).

^b A total of 4 deaths were reported across the 2 trials. In TRIUMPH-1-OSA, both deaths occurred in the placebo group (gunshot wound and cardiac arrest). In TRIUMPH-2-OSA, 1 death occurred in the placebo group (septic shock) and 1 in the retatrutide 9-mg group (upper GI hemorrhage).

^c MACE included deaths from cardiovascular causes.

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What were the baseline characteristics of participants in TRIUMPH-1-OSA and TRIUMPH-2-OSA?

Baseline demographic and clinical characteristics for both trials are presented in Table 4.

**Table 4. Baseline Demographic and Clinical Characteristics in TRIUMPH-1-OSA and TRIUMPH-2-OSA**³
Characteristic^a	TRIUMPH-1-OSA				TRIUMPH-2-OSA
Characteristic^a	RETA 4 mg (N=60)	RETA 9 mg (N=61)	RETA 12 mg (N=60)	PBO (N=62)	RETA 4 mg (N=116)	RETA 9 mg (N=109)	RETA 12 mg (N=110)	PBO (N=113)
Demographics
Age, years	47.8 ± 9.1	47.5 ± 11.0	46.4 ± 9.9	48.7 ± 11.8	53.7 ± 12.0	54.0 ± 10.8	54.2 ± 10.6	56.1 ± 11.0
Aged ≥65 years	2 (3)	6 (10)	4 (7)	5 (8)	21 (18)	19 (17)	23 (21)	28 (25)
Female	22 (37)	22 (36)	22 (37)	23 (37)	50 (43)	41 (38)	44 (40)	44 (39)
American Indian or Alaska Native^b	15 (25)	22 (36)	17 (28)	16 (26)	47 (41)	44 (40)	32 (29)	45 (40)
Asian^b	1 (2)	1 (2)	0	1 (2)	1 (1)	2 (2)	1 (1)	2 (2)
Black or African American^b	2 (3)	5 (8)	6 (10)	6 (10)	7 (6)	4 (4)	7 (6)	5 (4)
White^b	34 (57)	28 (46)	32 (53)	35 (56)	55 (47)	52 (48)	62 (56)	60 (53)
Multiple races^b	2 (3)	2 (3)	4 (7)	0	2 (2)	5 (5)	4 (4)	0
Hispanic or Latino^b	46 (77)	52 (85)	51 (85)	46 (74)	88 (76)	75 (69)	81 (74)	78 (69)
Anthropometric measures
Body weight, kg	123.5 ± 31.4	121.1 ± 24.8	115.4 ± 21.9	118.3 ± 24.2	115.1 ± 27.0	113.8 ± 22.8	121.4 ± 30.1	113.2 ± 25.8
BMI, kg/m²	43.7 ± 10.5	41.5 ± 7.6	39.9 ± 6.7	41.2 ± 6.7	40.9 ± 7.7	40.1 ± 7.2	41.9 ± 8.2	39.9 ± 7.6
BMI <30 kg/m²	4 (6.7)	1 (1.6)	1 (1.7)	0	8 (6.9)	2 (1.8)	6 (5.5)	10 (8.8)
BMI ≥30 to <35 kg/m²	3 (5.0)	8 (13.1)	11 (18.3)	10 (16.1)	14 (12.1)	28 (25.7)	15 (13.6)	20 (17.7)
BMI ≥35 to <40 kg/m²	19 (31.7)	20 (32.8)	28 (46.7)	24 (38.7)	35 (30.2)	29 (26.6)	31 (28.2)	36 (31.9)
BMI ≥40 to <50 kg/m²	21 (35.0)	24 (39.3)	15 (25.0)	20 (32.3)	43 (37.1)	36 (33.0)	41 (37.3)	35 (31.0)
BMI ≥50 kg/m²	13 (21.7)	8 (13.1)	5 (8.3)	8 (12.9)	16 (13.8)	14 (12.8)	17 (15.5)	12 (10.6)
Waist circumference, cm	125.9 ± 19.3	122.9 ± 16.5	120.0 ± 12.8	124.8 ± 14.4	124.7 ± 16.6	123.7 ± 14.4	127.4 ± 17.1	123.1 ± 14.6
Neck circumference, cm	45.0 ± 4.8	44.8 ± 4.6	44.1 ± 4.3	44.9 ± 4.5	44.0 ± 5.0	43.6 ± 5.1	45.3 ± 5.3	43.7 ± 5.4
Sleep apnea characteristics
AHI^c, events/h	61.4 ± 35.7	59.6 ± 32.9	56.2 ± 28.0	57.1 ± 28.1	54.7 ± 34.0	58.2 ± 32.2	57.4 ± 31.3	53.5 ± 26.3
Mild OSA (AHI 5 to <15 events/h)	0	0	0	0	0	2 (2)	2 (2)	0
Moderate OSA (AHI ≥15 events/h)	14 (23)	15 (25)	16 (27)	11 (18)	36 (31)	26 (24)	27 (25)	26 (23)
Severe OSA (AHI ≥30 events/h)	46 (77)	46 (75)	44 (73)	51 (82)	79 (69)	80 (74)	80 (73)	87 (77)
SASHB^d, %min/h	227.2 ± 165.6	228.0 ± 198.7	209.7 ± 182.5	207.0 ± 171.1	223.8 ± 249.5	222.7 ± 191.1	251.5 ± 251.2	194.0 ± 166.7
PROMIS-SRI^e T-score	56.3 ± 7.6	55.8 ± 8.6	56.7 ± 6.9	58.6 ± 9.1	55.4 ± 7.9	54.5 ± 9.1	54.2 ± 8.8	53.5 ± 8.1
PROMIS-SD^e T-score	56.1 ± 7.1	55.9 ± 6.8	54.4 ± 7.0	58.7 ± 7.5	53.2 ± 5.7	53.2 ± 5.2	53.3 ± 5.6	52.8 ± 5.2
ESS^f score	12.0 ± 5.3	11.4 ± 5.6	10.4 ± 5.8	11.7 ± 5.6	10.5 ± 5.6	9.9 ± 5.5	9.2 ± 5.7	9.5 ± 4.9
PAP therapy use	19 (32)	20 (33)	18 (30)	19 (31)	32 (28)	30 (28)	29 (26)	35 (31)
Duration of OSA^g, years	4.0 ± 4.9	4.9 ± 6.2	4.1 ± 4.7	4.7 ± 5.0	5.5 ± 6.0	5.4 ± 5.6	5.8 ± 6.9	6.3 ± 7.0
Cardiometabolic measures
SBP, mm Hg	127.4 ± 13.0	129.9 ± 12.4	129.8 ± 10.0	129.4 ± 10.5	127.9 ± 14.1	129.1 ± 15.1	130.6 ± 13.0	129.8 ± 13.5
DBP, mm Hg	83.4 ± 8.7	83.3 ± 9.2	84.7 ± 7.5	84.6 ± 9.1	80.9 ± 9.5	80.5 ± 10.0	81.7 ± 8.8	80.5 ± 8.6
hsCRP, mg/L	7.6 ± 7.5	7.0 ± 6.9	6.2 ± 5.3	6.9 ± 7.5	7.5 ± 10.4	6.4 ± 7.7	6.4 ± 7.1	6.7 ± 13.8
HbA1c, %	5.7 ± 0.4	5.8 ± 0.4	5.6 ± 0.4	5.8 ± 0.4	7.7 ± 1.1	7.7 ± 1.2	7.6 ± 1.2	7.7 ± 1.2
HbA1c, mmol/mol	38.9 ± 4.1	39.6 ± 3.9	38.2 ± 4.4	39.9 ± 3.8	60.6 ± 11.5	60.7 ± 12.8	59.9 ± 12.8	60.8 ± 13.3
Fasting insulin, mIU/L	30.4 ± 21.6	30.8 ± 25.7	29.3 ± 17.5	31.9 ± 24.7	30.8 ± 20.7	29.6 ± 19.0	34.3 ± 22.2	29.2 ± 26.9
Total cholesterol, mg/dL	185.8 ± 36.7	184.1 ± 34.6	183.0 ± 29.5	187.0 ± 38.7	170.0 ± 42.2	180.4 ± 45.4	176.9 ± 42.0	175.0 ± 40.1
Triglycerides, mg/dL	144.4 ± 66.4	137.7 ± 53.0	155.4 ± 81.9	155.9 ± 58.2	171.5 ± 121.5	184.5 ± 106.0	178.8 ± 102.7	164.2 ± 78.3
Non-HDL cholesterol, mg/dL	142.2 ± 35.8	138.9 ± 35.1	139.1 ± 28.7	142.6 ± 37.0	127.7 ± 42.5	137.7 ± 44.4	133.7 ± 40.9	132.1 ± 39.8
LDL cholesterol, mg/dL	113.6 ± 31.2	111.6 ± 30.9	108.5 ± 24.9	111.6 ± 33.0	94.7 ± 36.7	100.9 ± 37.3	98.9 ± 36.4	99.5 ± 35.2
VLDL cholesterol, mg/dL	28.9 ± 13.3	27.6 ± 10.6	30.3 ± 13.7	31.2 ± 11.6	29.7 ± 12.9	34.4 ± 14.3	33.8 ± 15.5	31.9 ± 13.5
Medical history
Duration of obesity, years	21.7 ± 12.1	18.7 ± 11.4	18.5 ± 9.7	20.6 ± 11.2	20.2 ± 10.8	22.9 ± 12.0	24.2 ± 12.1	24.0 ± 14.4
Duration of T2D, years	NA	NA	NA	NA	7.4 ± 8.0	5.6 ± 6.0	6.9 ± 6.5	8.6 ± 7.8
Hypertension^h	27 (45.0)	35 (57.4)	24 (40.0)	34 (54.8)	84 (72.4)	75 (68.8)	81 (73.6)	80 (70.8)
Prediabetes^h	25 (41.7)	26 (42.6)	23 (38.3)	28 (45.2)	NA	NA	NA	NA
Dyslipidemia^h	17 (28.3)	24 (39.3)	21 (35.0)	29 (46.8)	72 (62.1)	69 (63.3)	77 (70.0)	77 (68.1)

Abbreviations: AHI = apnea-hypopnea index; BMI = body mass index; DBP = diastolic blood pressure; ESS = Epworth Sleepiness Scale; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; hsCRP = high-sensitivity C-reactive protein; LDL = low-density lipoprotein; N = number of randomized participants in each treatment group; n = number of participants in the subgroup; NA = not applicable; OSA = obstructive sleep apnea; PAP = positive airway pressure; PBO = placebo; PROMIS-SD = Patient-Reported Outcomes Measurement Information System Sleep Disturbance; PROMIS-SRI = Patient-Reported Outcomes Measurement Information System Sleep-Related Impairment; RETA = retatrutide; SASHB = sleep apnea-specific hypoxic burden; SBP = systolic blood pressure; T2D = type 2 diabetes; VLDL = very-low-density lipoprotein.
Notes: Percentages are based on participants with nonmissing data and might not sum to 100%.
^a Data are mean ± SD or n (%), unless otherwise indicated.

^bRace and ethnic groups were reported by the participants.

^c The AHI is the number of apneas and hypopneas per hour of sleep and is used to define the severity of OSA. In TRIUMPH-2-OSA, data on the AHI at baseline were missing for 1 participant in the 4-mg group, 1 in the 9-mg group, and 1 in the 12-mg group.

^d The SASHB is the total respiratory event–related area under the oxygen-desaturation curve from a pre-event baseline and is expressed as percent-minutes per hour — the time (in minutes) spent in oxygen desaturation (%) per hour of sleep. This measure is calculated from a polysomnographic study that encapsulates frequency, duration, and depth of respiratory event–related oxygen desaturation. In TRIUMPH-2-OSA, data on the SASHB at baseline were missing for 1 participant in the 4-mg group, 1 in the 9-mg group, and 1 in the 12-mg group.

^e The PROMIS-SRI consists of 8 factors that the participant can recall in the past 7 days, with each factor rated on a 5-point scale from “not at all” to “very much.” The PROMIS-SD consists of 8 factors that the participant can recall in the past 7 days, with each factor rated on a 5-point scale from “not at all” to “very much,” “never” to “always,” or “very poor” to “very good.” Scores for individual factors were totaled to obtain a raw score that was then converted to a T-score (with the use of response-pattern scoring), with a mean score of 50±10; higher scores indicate more sleep-related impairment or sleep disturbance. Both scores at baseline were missing for 8 participants in the 4-mg group, 5 in the 9-mg group, 8 in the 12-mg group, and 6 in the placebo group in TRIUMPH-1-OSA and for 10, 8, 8, and 10, respectively, in TRIUMPH-2-OSA.

^f The ESS is an 8-factor participant-reporting measure that asks the participant to rate, on a scale of 0 (would never doze) to 3 (high chance of dozing), their recent typical likelihood of dozing in 8 different daytime situations. The ESS total score is the sum of the 8-factor scores and ranges from 0 to 24, with higher scores indicating greater daytime sleepiness. The score at baseline was missing for 8 participants in the 4-mg group, 5 in the 9-mg group, 8 in the 12-mg group, and 6 in the placebo group in TRIUMPH-1-OSA and for 10, 8, 8, and 11, respectively, in TRIUMPH-2-OSA.

^g In TRIUMPH-2-OSA, data on the duration of OSA were missing for 1 participant in the 4-mg group.

^h Comorbidities were assessed through a review of medical history.

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References

The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).

Giblin K, Kaplan LM, Somers VK, et al. Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: rationale and design of the TRIUMPH registrational clinical trials. Diabetes Obes Metab. 2026;28(1):83-93. https://doi.org/10.1111/dom.70209
Jastreboff AM, Kaplan LM, Frías JP, et al; Retatrutide Phase 2 Obesity Trial Investigators. Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial. N Engl J Med. 2023;389(6):514-526. https://doi.org/10.1056/nejmoa2301972
Grunstein RR, Somers VK, Azarbarzin A, et al. Retatrutide once weekly for treatment of obstructive sleep apnea. N Engl J Med. 2026. Published online October 21, 2026. https://doi.org/10.1056/NEJMoa2611477

Date of Last Review: October 09, 2026

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