Phase 3 · Tirzepatide

SURMOUNT-4 trial results

Efficacy and Safety of Tirzepatide Once Weekly Versus Placebo for Maintenance of Weight Loss in Participants Without Type 2 Diabetes Who Have Obesity or Are Overweight With Weight-Related Comorbidities: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-4)

Percent Change From Randomization in Body Weight at Week 88 (percent change), Randomization (Week 36), Week 88. Placebo: 14.8; Tirzepatide MTD: -6.7.

Participants: 783
Status: completed
Completed: 2023-05-18
Sponsor: Eli Lilly and Company

As posted on ClinicalTrials.gov (NCT04660643), updated at source May 22, 2024. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What SURMOUNT-4 measured first

Percent Change From Randomization in Body Weight at Week 88percent change · Randomization (Week 36), Week 88 · least squares mean

Placebon=329	Tirzepatide MTDn=332
14.8(0.53)	-6.7(0.52)

Side effects by arm

Side effects in SURMOUNT-4

Percent of participants affected, Week 0 to 36 for the open-label lead-in period arm, Week 36 to 92 for the double-blind study period arms.. The most common events the registry lists.

Event	Tirzepatide (lead-in)	Placebo	Tirzepatide MTD
Any serious event	2%	3%	3%
Nausea	35.5%	2.7%	8.1%
Diarrhoea	21.1%	4.8%	10.7%
Constipation	20.7%	2.4%	3.6%
Vomiting	16.4%	1.2%	5.4%
Covid-19	10.5%	14.9%	14%
Decreased appetite	9.5%	1.2%	2.1%
Gastrooesophageal reflux disease	8.8%	0.3%	1.2%
Injection site reaction	8.2%	0.6%	2.1%
Dyspepsia	8.1%	0.3%	0.3%
Headache	7.2%	3%	1.5%
Fatigue	6.8%	0.6%	2.7%
Abdominal pain	6.1%	1.8%	3.3%
Upper respiratory tract infection	3.3%	5.4%	2.4%
Alopecia	5.1%	1.5%	3.9%

Secondary outcomes

What else it measured

Percent Change From Randomization in Body Weight at Week 64percent change · Randomization (Week 36), Week 64 · least squares mean

Placebon=329	Tirzepatide MTDn=332
9.9(0.38)	-6.0(0.37)

Change From Randomization in Body Weightkilogram (kg) · Randomization (Week 36), Week 88 · least squares mean

Placebon=329	Tirzepatide MTDn=332
11.9(0.43)	-5.7(0.42)

Change From Randomization in Waist Circumferencecentimetre (cm) · Randomization (Week 36), Week 88 · least squares mean

Placebon=329	Tirzepatide MTDn=332
8.3(0.44)	-4.6(0.43)

Change From Randomization in Body Mass Index (BMI)kilogram per square metre (kg/m^2) · Randomization (Week 36), Week 88 · least squares mean

Placebon=329	Tirzepatide MTDn=332
4.3(0.16)	-2.1(0.15)

Change From Randomization in Fasting Glucosemilligrams per deciliter (mg/dL) · Randomization (Week 36), Week 88 · least squares mean

Placebon=310	Tirzepatide MTDn=325
7.74(0.548)	-0.90(0.528)

Change From Randomization in Hemoglobin A1c (HbA1c)percentage of HbA1c · Randomization (Week 36), Week 88 · least squares mean

Placebon=311	Tirzepatide MTDn=325
0.25(0.017)	-0.08(0.017)

Percent Change From Randomization in Fasting Insulinpercent change · Randomization (Week 36), Week 88 · least squares mean

Placebon=311	Tirzepatide MTDn=324
23.3(4.37)	-15.4(2.88)

Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA))percent change · Randomization (Week 36), Week 88 · least squares mean

Measure	Placebon=273	Tirzepatide MTDn=298
Total Cholesterol	8.30(0.943)	2.29(0.852)
LDL Cholesterol	3.43(1.368)	-3.36(1.218)
HDL Cholesterol	14.6(1.06)	18.3(1.05)
VLDL Cholesterol	14.7(2.32)	-7.8(1.77)
Triglycerides	15.6(2.39)	-8.2(1.81)
FFA	-2.9(2.98)	-13.4(2.54)

Change From Randomization in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)millimetre of mercury (mmHg) · Randomization (Week 36), Week 88 · least squares mean

Measure	Placebon=329	Tirzepatide MTDn=332
SBP	8.4(0.64)	2.1(0.61)
DBP	3.2(0.44)	-0.4(0.42)

Change From Randomization in Short Form 36 Version 2 Health Survey (SF 36v2) Acute Form - Physical Functioning Domain ScoreT-score · Randomization (Week 36), Week 88 · least squares mean

Placebon=270	Tirzepatide MTDn=295
-1.8(0.32)	0.8(0.31)

Change From Randomization in Impact of Weight on Quality of Life Lite Clinical Trials Version (IWQOL-Lite-CT) - Physical Function Composite Scorescore on a scale · Randomization (Week 36), Week 88 · least squares mean

Placebon=272	Tirzepatide MTDn=293
-5.0(0.95)	4.4(0.91)

Percentage of Participants Who Maintain at Least 80% of the Body Weight Lost During the Open-Label Lead-In Periodpercentage of participants · Week 88 · number

Placebon=326	Tirzepatide MTDn=332
13.50	93.37

The trial

How SURMOUNT-4 was run

This was a study of tirzepatide in participants with obesity or overweight. The main purpose was to learn more about how tirzepatide maintained body weight loss. The study had two phases: a lead-in phase in which all participants took tirzepatide and a treatment phase in which participants either continued tirzepatide or switched to placebo. The study lasted about 2 years (25 visits).

Tirzepatide (lead-in): Participants received weekly doses of tirzepatide subcutaneously (SC) for 36 weeks, starting at 2.5 milligrams (mg) and increasing by 2.5 mg every 4 weeks, as tolerated, up to the maximum tolerated dose (MTD) of either 10 mg or 15 mg.
Tirzepatide MTD: Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
Placebo: Participants received weekly doses of placebo SC for 52 weeks.

Who could join the trial

Inclusion Criteria: * Body Mass Index (BMI) ≥30 kilograms per square meter (kg/m²), or ≥27 kg/m² and previous diagnosis with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease * History of at least one unsuccessful dietary effort to lose body weight Exclusion Criteria: * Diabetes mellitus * Change in body weight greater than 5 kg within 3 months prior to starting study * Obesity induced by other endocrinologic disorders or monogenetic or syndromic forms of obesity * History of pancreatitis * Family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2) * History of significant active or unstable major depressive disorder (MDD) or other severe psychiatric disorder within the last 2 years * Any lifetime history of a suicide attempt

Published papers

Papers from SURMOUNT-4

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

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