Phase 3 · Tirzepatide

NCT03861039 trial results

A Phase 3, Long-Term Safety Study of Tirzepatide in Combination With Monotherapy of Oral Antihyperglycemic Medications in Patients With Type 2 Diabetes Mellitus (SURPASS J-combo)

Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration (Participants), Baseline through Week 52. 5 mg Tirzepatide: 0; 10 mg Tirzepatide: 1; 15 mg Tirzepatide: 1.

Participants
443
Status
completed
Completed
2021-02-16
Sponsor
Eli Lilly and Company

As posted on ClinicalTrials.gov (NCT03861039), updated at source Feb 14, 2022. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What NCT03861039 measured first

Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug AdministrationParticipants · Baseline through Week 52 · count of participants
5 mg Tirzepatiden=14810 mg Tirzepatiden=14715 mg Tirzepatiden=148
011
Side effects by arm

Side effects in NCT03861039

Percent of participants affected, Baseline through Week 56. The most common events the registry lists.

Event5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
Any serious event1.4%7.5%7.4%
Nausea9.5%13.6%27%
Nasopharyngitis18.9%13.6%18.2%
Constipation8.1%13.6%14.9%
Diarrhoea7.4%13.6%13.5%
Decreased appetite7.4%10.2%12.2%
Vomiting2.7%7.5%10.1%
Dyspepsia4.1%7.5%3.4%
Abdominal discomfort6.1%4.8%5.4%
Lipase increased2.7%2.7%6.1%
Vulvovaginal candidiasis0%5.9%2.3%
Weight decreased0.7%5.4%4.1%
Back pain2.7%5.4%0%
Dizziness0.7%1.4%5.4%
Gastroenteritis4.7%3.4%2.7%
Abdominal distension3.4%4.1%4.1%
Gastrooesophageal reflux disease2.7%4.1%2.7%
Malaise1.4%2%4.1%
Abdominal pain upper1.4%2.7%3.4%
Influenza3.4%0.7%1.4%
Menorrhagia0%2.9%0%
Vulvovaginal inflammation0%2.9%0%
Gastrointestinal disorder0.7%0%2.7%
Injection site reaction2.7%2%2.7%
Herpes zoster0.7%2.7%2%
Arthralgia1.4%1.4%2.7%
Secondary outcomes

What else it measured

Change From Baseline in Hemoglobin A1c (HbA1c)Percentage of HbA1c · Baseline, Week 52 · least squares mean
5 mg Tirzepatiden=14810 mg Tirzepatiden=14615 mg Tirzepatiden=145
-2.57(0.075)-2.98(0.075)-3.02(0.077)
Percentage of Participants Who Achieve HbA1c <7%percentage of participants · Week 52 · number
5 mg Tirzepatiden=14810 mg Tirzepatiden=14615 mg Tirzepatiden=145
92.5797.9596.55
Change From Baseline in Fasting Serum Glucosemilligram per Deciliter (mg/dL) · Baseline, Week 52 · least squares mean
5 mg Tirzepatiden=14810 mg Tirzepatiden=14615 mg Tirzepatiden=145
-58.6(1.75)-71.2(1.75)-74.4(1.81)
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Valuesmg/dL · Baseline, Week 52 · least squares mean
5 mg Tirzepatiden=13610 mg Tirzepatiden=13515 mg Tirzepatiden=125
-80.0(1.91)-94.1(1.92)-96.3(1.99)
Change From Baseline in Body WeightKilograms (kg) · Baseline, Week 52 · least squares mean
5 mg Tirzepatiden=14810 mg Tirzepatiden=14615 mg Tirzepatiden=145
-3.8(0.51)-7.5(0.51)-10.2(0.52)
Percentage of Participants Who Achieve Weight Loss of ≥5% From Baselinepercentage of participants · Week 52 · number
5 mg Tirzepatiden=14810 mg Tirzepatiden=14615 mg Tirzepatiden=145
43.9270.5584.14
Change From Baseline in Fasting Insulinpicomol per liter (pmol/L) · Baseline, Week 52 · least squares mean
5 mg Tirzepatiden=14310 mg Tirzepatiden=14415 mg Tirzepatiden=134
6.2(2.68)-4.8(2.21)-7.7(2.16)
Change From Baseline in Fasting C-Peptidemicrograms/litre (ug/L) · Baseline, Week 52 · least squares mean
5 mg Tirzepatiden=14310 mg Tirzepatiden=14415 mg Tirzepatiden=134
-0.12(0.044)-0.28(0.040)-0.34(0.040)
Change From Baseline in Homeostasis Model Assessment B (HOMA-2B) (Insulin)percentage of HOMA-2B · Baseline, Week 52 · least squares mean
5 mg Tirzepatiden=13910 mg Tirzepatiden=13515 mg Tirzepatiden=128
39.7(2.16)44.9(2.40)49.2(2.60)
Change From Baseline in HOMA-2S (Insulin)Percentage of HOMA-2S · Baseline, Week 52 · least squares mean
5 mg Tirzepatiden=13910 mg Tirzepatiden=13515 mg Tirzepatiden=128
-0.1(3.37)16.7(4.23)24.1(4.66)
Number of Participants With Hypoglycemia Incidence and Rate With Blood Glucose <54 mg/dL or Severe Hypoglycemia, Exclude Hypoglycemic Events Occurring After Initiation of a New Antihyperglycemic TherapyParticipants · Baseline through Week 56 · count of participants
5 mg Tirzepatiden=14810 mg Tirzepatiden=14715 mg Tirzepatiden=148
113
Number of Participants With Anti-Tirzepatide AntibodiesParticipants · Baseline through Week 52 · count of participants
5 mg Tirzepatiden=14810 mg Tirzepatiden=14715 mg Tirzepatiden=148
878288
The trial

How NCT03861039 was run

The purpose of this study is to determine the long-term safety of the study drug tirzepatide in combination with oral antihyperglycemic medications in participants with type 2 diabetes.

  • 5 mg Tirzepatide: 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
  • 10 mg Tirzepatide: 10 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
  • 15 mg Tirzepatide: 15 mg tirzepatide administered SC once a week. Participant received the following pre-treatment oral antihyperglycemic medication (OAM): Sulfonylurea, biguanide, alpha-glucosidase inhibitor, thiazolidinedione, glinide, or sodium-glucose cotransporter type 2 inhibitor.
Who could join the trial

Inclusion Criteria: Participant must: * Have been diagnosed with type 2 diabetes mellitus based on the World Health Organization classification before the screening visit. * Have HbA1c ≥7.0% to \<11.0%, as determined by the central laboratory at screening. * Have been taking sulfonylureas, biguanides, thiazolidinedione, alpha-glucosidase inhibitor, glinides, or sodium-glucose cotransporter type 2 inhibitor monotherapy for at least 3 months before screening and have been on the following dose for at least 8 weeks before screening. * Have body mass index (BMI) of ≥23 kilograms per meter squared at screening. * Be of stable weight (±5%) during 3 months preceding screening; and agree to not initiate an intensive diet and/or exercise program during the study with the intent of reducing body weight other than the lifestyle and dietary measures for diabetes treatment. Exclusion Criteria: Participant must not: * Have type 1 diabetes mellitus. * Have had chronic or acute pancreatitis any time prior to study entry. * Have proliferative diabetic retinopathy or diabetic maculopathy or nonproliferative diabetic retinopathy requiring immediate or urgent treatment. * Have disorders associated with slowed emptying of the stomach, or have had any stomach surgeries for the purpose of weight loss. * Have acute or chronic hepatitis, signs and symptoms of any other liver disease, or blood alanine transaminase (ALT) enzyme level \>3.0 times the upper limit of normal (ULN) for the reference range, as determined by the central laboratory. Participants with nonalcoholic fatty liver disease (NAFLD) are eligible for participation in this trial only if there ALT level is ≤3.0 the ULN for the reference range. * Have had a heart attack, stroke, or hospitalization for congestive heart failure in the past 2 months. * Have a personal or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia syndrome type 2. * Have been taking weight loss drugs, including over-the-counter medications during the last 3 months.

Published papers

Papers from NCT03861039

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

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