Primary outcome
What NCT00734474 measured first
| 1.5 mg LY2189265n=301 | 0.75 mg LY2189265n=297 | Sitagliptinn=311 |
|---|---|---|
| -1.10(0.06) | -0.87(0.06) | -0.39(0.06) |
Phase 2 and Phase 3 · Dulaglutide
NCT00734474 trial results
A Phase 2/3, Placebo-Controlled, Efficacy and Safety Study of Once-Weekly, Subcutaneous LY2189265 Compared to Sitagliptin in Patients With Type 2 Diabetes Mellitus on Metformin
Glycosylated Hemoglobin (HbA1c) Change From Baseline (percentage of HbA1c), Baseline, 52 weeks. 1.5 mg LY2189265: -1.10; 0.75 mg LY2189265: -0.87; Sitagliptin: -0.39.
- Participants
- 1,202
- Status
- completed
- Completed
- 2012-07
- Sponsor
- Eli Lilly and Company
As posted on ClinicalTrials.gov (NCT00734474), updated at source Apr 20, 2015. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.
Side effects by arm
Side effects in NCT00734474
Percent of participants affected. The most common events the registry lists.
| Event | 3.0 mg LY2189265 | 2.0 mg LY2189265 | 1.5 mg LY2189265 | 1.0 mg LY2189265 | 0.75 mg LY2189265 | 0.5 mg LY2189265 | 0.25 mg LY2189265 | Sitagliptin | Placebo/Sitagliptin (Baseline Through 104 Weeks) |
|---|---|---|---|---|---|---|---|---|---|
| Any serious event | 6.7% | 3.3% | 11.8% | 0% | 7.6% | 4% | 0% | 10.2% | 9.6% |
| Nausea | 33.3% | 20% | 17.4% | 40% | 14.6% | 12% | 8.3% | 7% | 5.1% |
| Gastritis | 0% | 3.3% | 3.6% | 20% | 1.3% | 0% | 0% | 2.9% | 4% |
| Vomiting | 13.3% | 13.3% | 13.5% | 20% | 8.3% | 4% | 4.2% | 3.5% | 1.7% |
| Diarrhoea | 0% | 16.7% | 16.4% | 10% | 11.9% | 16% | 8.3% | 5.7% | 8.5% |
| Nasopharyngitis | 0% | 3.3% | 14.1% | 0% | 15.9% | 4% | 0% | 14.9% | 14.1% |
| Hyperglycaemia | 0% | 0% | 9.9% | 0% | 12.6% | 0% | 0% | 15.6% | 15.8% |
| Gastroenteritis | 13.3% | 0% | 3.9% | 0% | 2.3% | 4% | 0% | 1.9% | 4% |
| Constipation | 6.7% | 0% | 4.6% | 0% | 5.3% | 12% | 0% | 1.3% | 0.6% |
| Dyspepsia | 0% | 3.3% | 5.9% | 10% | 6.3% | 12% | 4.2% | 5.1% | 2.3% |
| Visual acuity reduced | 0% | 0% | 0.3% | 10% | 0% | 0% | 0% | 0% | 0% |
| Abdominal discomfort | 0% | 10% | 3.3% | 0% | 1% | 0% | 4.2% | 2.2% | 0.6% |
| Abdominal distension | 0% | 0% | 4.3% | 10% | 5% | 8% | 0% | 1% | 0.6% |
| Chills | 0% | 0% | 0% | 10% | 0% | 0% | 0% | 0.3% | 0% |
| Fatigue | 0% | 0% | 4.3% | 10% | 3% | 0% | 8.3% | 3.5% | 3.4% |
| Temperature intolerance | 0% | 0% | 0% | 10% | 0% | 0% | 0% | 0% | 0% |
| Amylase increased | 0% | 0% | 2% | 10% | 1.7% | 4% | 0% | 1.9% | 0.6% |
| Blood calcitonin increased | 0% | 0% | 0.7% | 10% | 0% | 0% | 0% | 0.6% | 0.6% |
| Decreased appetite | 0% | 10% | 9.5% | 10% | 5.6% | 8% | 4.2% | 3.5% | 1.7% |
| Synovial cyst | 0% | 0% | 0% | 10% | 0% | 0% | 0% | 0% | 0% |
| Depression | 0% | 0% | 2.3% | 10% | 1.3% | 4% | 0% | 1.6% | 0.6% |
| Ingrowing nail | 0% | 0% | 0% | 10% | 0.7% | 0% | 4.2% | 0% | 0.6% |
| Headache | 0% | 3.3% | 9.5% | 0% | 8.9% | 4% | 4.2% | 8.3% | 6.8% |
| Back pain | 0% | 0% | 6.9% | 0% | 9.3% | 8% | 0% | 6% | 5.1% |
| Sinusitis | 0% | 3.3% | 4.9% | 0% | 3.3% | 8% | 0% | 2.2% | 1.7% |
| Lipase increased | 0% | 0% | 3.6% | 0% | 4.3% | 8% | 4.2% | 4.8% | 2.8% |
Secondary outcomes
What else it measured
| 3.0 mg LY2189265n=10 | 2.0 mg LY2189265n=26 | 1.5 mg LY2189265n=20 | 1.0 mg LY2189265n=8 | 0.75 mg LY2189265n=20 | 0.5 mg LY2189265n=21 | 0.25 mg LY2189265n=14 | Sitagliptinn=30 | Placebo/Sitagliptin (Baseline Through 26 Weeks)n=28 |
|---|---|---|---|---|---|---|---|---|
| -1.09(0.77) | -1.25(0.68) | -1.49(1.12) | -0.98(0.47) | -1.02(0.99) | -0.94(0.65) | -0.70(0.49) | -0.76(0.86) | -0.06(0.64) |
| Measure | 1.5 mg LY2189265n=301 | 0.75 mg LY2189265n=297 | Sitagliptinn=311 | Placebo/Sitagliptin (Baseline Through 26 Weeks)n=176 |
|---|---|---|---|---|
| 26 Weeks | -1.22(0.05) | -1.01(0.06) | -0.61(0.05) | 0.03(0.07) |
| 104 Weeks | -0.99(0.06) | -0.71(0.07) | -0.32(0.06) | NA(NA) |
| Measure | 1.5 mg LY2189265n=303 | 0.75 mg LY2189265n=302 | Sitagliptinn=314 | Placebo/Sitagliptin (Baseline Through 26 Weeks)n=177 |
|---|---|---|---|---|
| 26 Weeks Versus 13 Weeks (n=269, 269, 276, 136) | -0.03(0.04) | 0.02(0.04) | 0.00(0.04) | -0.14(0.05) |
| 52 Weeks Versus 26 Weeks (n=245, 254, 250) | 0.14(0.05) | 0.16(0.05) | 0.24(0.05) | NA(NA) |
| 104 Weeks Versus 52 Weeks (n=194, 191, 190) | 0.13(0.06) | 0.16(0.06) | 0.09(0.06) | NA(NA) |
| Measure | 1.5 mg LY2189265n=297 | 0.75 mg LY2189265n=296 | Sitagliptinn=308 | Placebo/Sitagliptin (Baseline Through 26 Weeks)n=176 |
|---|---|---|---|---|
| 26 Weeks (n=265, 271, 276, 135) | -2.38(0.12) | -1.97(0.12) | -0.97(0.11) | -0.49(0.16) |
| 52 Weeks (n=239, 247, 244) | -2.38(0.13) | -1.63(0.13) | -0.90(0.13) | NA(NA) |
| 104 Weeks (n=190, 187, 181) | -1.99(0.15) | -1.39(0.15) | -0.47(0.15) | NA(NA) |
| Measure | 1.5 mg LY2189265n=254 | 0.75 mg LY2189265n=261 | Sitagliptinn=247 | Placebo/Sitagliptin (Baseline Through 26 Weeks)n=122 |
|---|---|---|---|---|
| 26 Weeks (n=238, 249, 230, 115) | 11.59(6.57) | 10.15(6.51) | 8.48(6.68) | -6.92(9.24) |
| 52 Weeks (n=207, 218, 200) | 10.57(5.95) | 12.95(5.88) | 4.18(6.01) | NA(NA) |
| 104 Weeks (n=187, 200, 183) | 11.36(7.58) | 21.56(7.40) | 0.29(7.64) | NA(NA) |
| 3.0 mg LY2189265n=14 | 2.0 mg LY2189265n=30 | 1.5 mg LY2189265n=23 | 1.0 mg LY2189265n=9 | 0.75 mg LY2189265n=20 | 0.5 mg LY2189265n=22 | 0.25 mg LY2189265n=17 | Sitagliptinn=35 | Placebo/Sitagliptin (Baseline Through 26 Weeks)n=33 |
|---|---|---|---|---|---|---|---|---|
| -3.32(3.37) | -2.15(1.97) | -2.12(1.93) | -2.23(1.63) | -1.17(2.30) | -1.53(1.88) | -0.85(1.47) | -0.43(1.78) | -0.56(1.69) |
| Measure | 1.5 mg LY2189265n=303 | 0.75 mg LY2189265n=299 | Sitagliptinn=314 | Placebo/Sitagliptin (Baseline Through 26 Weeks)n=177 |
|---|---|---|---|---|
| 26 Weeks | -3.18(0.18) | -2.63(0.19) | -1.46(0.18) | -1.47(0.24) |
| 52 Weeks | -3.03(0.22) | -2.60(0.23) | -1.53(0.22) | NA(NA) |
| 104 Weeks | -2.88(0.25) | -2.39(0.26) | -1.75(0.25) | NA(NA) |
| Measure | 1.5 mg LY2189265n=304 | 0.75 mg LY2189265n=302 | Sitagliptinn=315 | Placebo/Sitagliptin (Baseline Through 26 Weeks)n=177 |
|---|---|---|---|---|
| 26 Weeks Versus 13 Weeks (n=271, 278, 282, 138) | -0.53(0.14) | -0.57(0.14) | -0.42(0.13) | -0.37(0.18) |
| 52 Weeks Versus 26 Weeks (n=246, 255, 253) | 0.17(0.18) | 0.06(0.18) | -0.04(0.18) | NA(NA) |
| 104 Weeks Versus 26 Weeks (n=197, 192, 191) | 0.42(0.23) | 0.32(0.24) | -0.39(0.23) | NA(NA) |
| Measure | 1.5 mg LY2189265n=299 | 0.75 mg LY2189265n=301 | Sitagliptinn=312 | Placebo/Sitagliptin (Baseline Through 26 Weeks)n=175 |
|---|---|---|---|---|
| 26 Weeks (n=266, 273, 277, 138) | -2.89(0.24) | -1.78(0.24) | -1.45(0.24) | -1.20(0.32) |
| 52 Weeks (n=238, 250, 247) | -2.91(0.29) | -2.05(0.29) | -1.45(0.29) | NA(NA) |
| 104 Weeks (n=192, 189, 188) | -2.57(0.35) | -1.75(0.35) | -1.20(0.35) | NA(NA) |
| Measure | 1.5 mg LY2189265n=302 | 0.75 mg LY2189265n=297 | Sitagliptinn=312 | Placebo/Sitagliptin (Baseline Through 26 Weeks)n=176 |
|---|---|---|---|---|
| <7.0% at 26 Weeks | 60.9 | 55.2 | 37.8 | 21.0 |
| <7.0% at 52 Weeks | 57.6 | 48.8 | 33.0 | NA |
| <7.0% at 104 Weeks | 54.3 | 44.8 | 31.1 | NA |
| ≤6.5% at 26 Weeks | 46.7 | 31.0 | 21.8 | 12.5 |
| ≤6.5% at 52 Weeks | 41.7 | 29.0 | 19.2 | NA |
| ≤6.5% at 104 Weeks | 39.1 | 24.2 | 14.1 | NA |
| Measure | 1.5 mg LY2189265n=304 | 0.75 mg LY2189265n=302 | Sitagliptinn=315 | Placebo/Sitagliptin (Baseline Through 26 Weeks)n=177 |
|---|---|---|---|---|
| Severe HE, 26 Weeks | 0 | 0 | 0 | 0 |
| Severe HE, 104 Weeks | 0 | 0 | 0 | NA |
| Documented Symptomatic HE, 26 Weeks | 17 | 8 | 10 | 2 |
| Documented Symptomatic HE, 104 Weeks | 33 | 19 | 18 | NA |
| Asymptomatic HE, 26 Weeks | 5 | 5 | 0 | 0 |
| Asymptomatic HE, 104 Weeks | 9 | 9 | 3 | NA |
| Nocturnal HE, 26 Weeks | 7 | 5 | 2 | 0 |
| Nocturnal HE, 104 Weeks | 14 | 13 | 10 | NA |
| Probable HE, 26 Weeks | 5 | 0 | 2 | 0 |
| Probable HE, 104 Weeks | 6 | 2 | 6 | NA |
| Measure | 1.5 mg LY2189265n=304 | 0.75 mg LY2189265n=302 | Sitagliptinn=315 | Placebo/Sitagliptin (Baseline Through 26 Weeks)n=177 |
|---|---|---|---|---|
| Severe HE, 26 Weeks | 0.0(0.0) | 0.0(0.0) | 0.0(0.0) | 0.0(0.0) |
| Severe HE, 104 Weeks | 0.0(0.0) | 0.0(0.0) | 0.0(0.0) | NA(NA) |
| Documented Symptomatic HE, 26 Weeks | 0.3(1.5) | 0.1(0.9) | 0.1(0.7) | 0.1(0.9) |
| Documented Symptomatic HE, 104 Weeks | 0.2(0.9) | 0.2(1.9) | 0.2(1.4) | NA(NA) |
| Asymptomatic HE, 26 Weeks | 0.1(0.8) | 0.1(0.5) | 0.0(0.0) | 0.0(0.0) |
| Asymptomatic HE, 104 Weeks | 0.1(0.4) | 0.0(0.2) | 0.0(0.1) | NA(NA) |
| Nocturnal HE, 26 Weeks | 0.1(0.9) | 0.1(0.6) | 0.0(0.4) | 0.0(0.0) |
| Nocturnal HE, 104 Weeks | 0.1(0.5) | 0.0(0.2) | 0.1(0.5) | NA(NA) |
| Probable Symptomatic HE, 26 Weeks | 0.0(0.4) | 0.0(0.0) | 0.0(0.2) | 0.0(0.0) |
| Probable Symptomatic HE, 104 Weeks | 0.0(0.1) | 0.0(0.0) | 0.0(0.1) | NA(NA) |
The trial
How NCT00734474 was run
This is an adaptive dose finding study and a Phase 3 efficacy study to evaluate the effects of once weekly injection of LY2189265 compared to Sitagliptin on glucose by measuring glycosylated hemoglobin (HbA1c) change from baseline after 52 weeks in participants with type 2 diabetes mellitus on Metformin.
- 3.0 mg LY2189265: LY2189265 (Dulaglutide): 3.0 milligrams (mg), subcutaneous (SC) injection, once weekly for up to 104 weeks Placebo: tablet, administered orally, once daily for up to 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for up to 104 weeks
- 2.0 mg LY2189265: LY2189265 (Dulaglutide): 2.0 milligrams (mg), subcutaneous (SC) injection, once weekly for up to 104 weeks Placebo: tablet, administered orally, once daily for up to 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for up to 104 weeks
- 1.5 mg LY2189265: LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for up to 104 weeks Placebo: tablet, administered orally, once daily for up to 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for up to 104 weeks
- 1.0 mg LY2189265: LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly for up to 104 weeks Placebo: tablet, administered orally, once daily for up to 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for up to 104 weeks
- 0.75 mg LY2189265: LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for up to 104 weeks Placebo: tablet, administered orally, once daily for up to 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for up to 104 weeks
- 0.5 mg LY2189265: LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly for up to 104 weeks Placebo: tablet, administered orally, once daily for up to 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for up to 104 weeks
- 0.25 mg LY2189265: LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly for up to 104 weeks Placebo: tablet, administered orally, once daily for up to 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for up to 104 weeks
- Sitagliptin: Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
- Placebo/Sitagliptin (Baseline Through 104 Weeks): Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Who could join the trial
Inclusion Criteria: * Diabetes mellitus, type 2, for at least 6 months * Treatment regimens: diet and exercise, metformin as monotherapy or in combination with another oral antihyperglycemic medication (OAM), or another OAM as monotherapy. Must be able to tolerate metformin at a dose of at least 1500 milligrams (mg) daily for 6 weeks prior to randomization. * Glycosylated hemoglobin (HbA1c) value of ≥7.0% to ≤9.5%, except participants on diet and exercise therapy who must have had HbA1c value of \>8.0% to ≤9.5% * Body mass index (BMI) between 25 and 40 kilograms per meter squared (kg/m\^2), inclusive * Stable weight for 3 months prior to screening * Females of childbearing potential must test negative for pregnancy and agree to use a reliable birth control method Exclusion Criteria: * Diabetes mellitus, type 1 * Use of a glucagon-like peptide-1 (GLP-1) analog (for example, exenatide) within 6 months prior to screening or are being treated with insulin * Gastric emptying abnormality, history of bariatric surgery, or chronic use of drugs that affect gastrointestinal motility * Use of medications to promote weight loss * Clinically-relevant cardiovascular event within 6 months prior to screening * Poorly controlled hypertension * Electrocardiogram (ECG) reading considered outside the normal limits or indicating cardiac disease * Liver disease, hepatitis, chronic pancreatitis, idiopathic acute pancreatitis, or alanine transaminase (ALT) levels \>3.0 times the upper limit of normal * Serum creatinine ≥1.5 milligrams per deciliter (mg/dL) or a creatinine clearance \<60 milliliters per minute (mL/minute) * Uncontrolled diabetes, defined as \>2 episodes of ketoacidosis or hyperosmolar state requiring hospitalization in the 6 months prior to study entry. * Uncontrolled endocrine or autoimmune abnormality * History of a transplanted organ * Chronic use of systemic glucocorticoid therapy * Active or untreated malignancy * Use of central nervous system (CNS) stimulants
Published papers
Papers from NCT00734474
- Ferdinand KC, Dunn J, Nicolay C, Sam F, Blue EK, Wang H. Weight-dependent and weight-independent effects of dulaglutide on blood pressure in patients with type 2 diabetes. Cardiovasc Diabetol. 2023 Mar 9;22(1):49. doi: 10.1186/s12933-023-01775-x.
- Sherman SI, Kloos RT, Tuttle RM, Pontecorvi A, Volzke H, Harper K, Vance C, Alston JT, Usborne AL, Sloop KW, Lakshmanan M. No calcitonin change in a person taking dulaglutide diagnosed with pre-existing medullary thyroid cancer. Diabet Med. 2018 Mar;35(3):381-385. doi: 10.1111/dme.13437.
- Boustani MA, Pittman I 4th, Yu M, Thieu VT, Varnado OJ, Juneja R. Similar efficacy and safety of once-weekly dulaglutide in patients with type 2 diabetes aged >/=65 and <65 years. Diabetes Obes Metab. 2016 Aug;18(8):820-8. doi: 10.1111/dom.12687. Epub 2016 Jun 7.
- Yu M, Van Brunt K, Varnado OJ, Boye KS. Patient-reported outcome results in patients with type 2 diabetes treated with once-weekly dulaglutide: data from the AWARD phase III clinical trial programme. Diabetes Obes Metab. 2016 Apr;18(4):419-24. doi: 10.1111/dom.12624. Epub 2016 Feb 4.
- Weinstock RS, Guerci B, Umpierrez G, Nauck MA, Skrivanek Z, Milicevic Z. Safety and efficacy of once-weekly dulaglutide versus sitagliptin after 2 years in metformin-treated patients with type 2 diabetes (AWARD-5): a randomized, phase III study. Diabetes Obes Metab. 2015 Sep;17(9):849-58. doi: 10.1111/dom.12479. Epub 2015 May 20.
- Skrivanek Z, Gaydos BL, Chien JY, Geiger MJ, Heathman MA, Berry S, Anderson JH, Forst T, Milicevic Z, Berry D. Dose-finding results in an adaptive, seamless, randomized trial of once-weekly dulaglutide combined with metformin in type 2 diabetes patients (AWARD-5). Diabetes Obes Metab. 2014 Aug;16(8):748-56. doi: 10.1111/dom.12305. Epub 2014 May 22.
- Spencer K, Colvin K, Braunecker B, Brackman M, Ripley J, Hines P, Skrivanek Z, Gaydos B, Geiger MJ. Operational challenges and solutions with implementation of an adaptive seamless phase 2/3 study. J Diabetes Sci Technol. 2012 Nov 1;6(6):1296-304. doi: 10.1177/193229681200600608.
Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.
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