Phase 3
Completed N=1,202
A Study of LY2189265 Compared to Sitagliptin in Participants With Type 2 Diabetes Mellitus on Metformin
Source: ClinicalTrials.gov NCT00734474 ↗Enrolled (actual)
1,202
Serious AEs
9.2%
Results posted
Jan 2015
Primary outcomePrimary: Glycosylated Hemoglobin (HbA1c) Change From Baseline — -1.10; -0.87; -0.39 percentage of HbA1c — p=<0.001
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Glycosylated Hemoglobin (HbA1c) Change From Baseline |
-1.22; -1.01; -0.61; 0.03; -0.99; -0.71 | <0.001 sig |
| SECONDARY Change From Baseline in Glycosylated Hemoglobin (HbA1c) at the Dose Decision Point |
-1.09; -1.25; -1.49; -0.98; -1.02; -0.94 | — |
| SECONDARY Glycosylated Hemoglobin (HbA1c) Change From Baseline |
-1.22; -1.01; -0.61; 0.03; -0.99; -0.71 | <0.001 sig |
| SECONDARY Durability of Change From Baseline in Glycosylated Hemoglobin (HbA1c) |
-0.03; 0.02; 0.00; -0.14; 0.14; 0.16 | — |
| SECONDARY Fasting Blood Glucose Change From Baseline |
-2.38; -1.97; -0.97; -0.49; -2.38; -1.63 | <0.001 sig |
| SECONDARY Fasting Insulin Change From Baseline |
11.59; 10.15; 8.48; -6.92; 10.57; 12.95 | 0.095 |
| SECONDARY Change From Baseline in Body Weight at Dose Decision Point |
-3.32; -2.15; -2.12; -2.23; -1.17; -1.53 | — |
| SECONDARY Body Weight Change From Baseline |
-3.18; -2.63; -1.46; -1.47; -3.03; -2.60 | <0.001 sig |
| SECONDARY Durability of Change From Baseline Body Weight |
-0.53; -0.57; -0.42; -0.37; 0.17; 0.06 | — |
| SECONDARY Waist Circumference Change From Baseline |
-2.89; -1.78; -1.45; -1.20; -2.91; -2.05 | <0.001 sig |
| SECONDARY Percentage of Participants Who Achieve Glycosylated Hemoglobin (HbA1c) <7% or ≤6.5% |
60.9; 55.2; 37.8; 21.0; 57.6; 48.8 | <0.001 sig |
| SECONDARY Incidence of Hypoglycemic Episodes |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Rate of Hypoglycemic Episodes |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Beta Cell Function and Insulin Sensitivity (HOMA2) |
32.28; 26.98; 10.81; 1.60; 33.57; 22.30 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events at 26 Weeks |
208; 204; 185; 111 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events at 52 Weeks |
9; 20; 233; 8; 231; 15 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events at 104 Weeks |
259; 255; 242 | — |
| SECONDARY Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks |
9; 3; 12; 3; 18; 24 | — |
| SECONDARY Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks |
10; 6; 16; 25; 27; 28 | — |
| SECONDARY Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks |
13; 11; 20; 29; 37; 39 | — |
| SECONDARY Number of Participants With Treatment-emergent Abnormal Lipid Tests |
16; 21; 20; 8; 34; 29 | — |
| SECONDARY Change From Baseline in Pulse Rate at Dose Decision Point |
6.63; 3.43; 2.39; 3.34; -1.63; 1.91 | — |
| SECONDARY Change From Baseline in Blood Pressure at Dose Decision Point |
-8.85; -4.63; -4.77; -2.00; -6.21; 0.40 | — |
| SECONDARY Change From Baseline in Pulse Rate |
2.57; 1.90; -0.11; -0.22; 2.28; 2.77 | — |
| SECONDARY Change From Baseline in Blood Pressure |
-1.73; -1.40; -1.94; 1.12; -0.07; 1.28 | — |
| SECONDARY Change From Baseline in Electrocardiogram (ECG) Parameters, Fridericia-corrected QT (QTcF) and PR Interval |
2.94; 1.60; 0.42; 2.24; 4.59; 3.06 | — |
| SECONDARY Participant-reported Outcomes, Impact of Weight on Quality of Life-Lite (IWQoL-Lite) |
83.41; 82.55; 83.97; 86.92; 86.31; 86.25 | — |
| SECONDARY Participant-reported Outcomes, EQ-5D |
0.80; 0.82; 0.84; 0.83; 0.84; 0.85 | — |
| SECONDARY Resource Utilization |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Pharmacokinetics of LY2189265: Area Under the Concentration-Time Curve |
13378; 7246 | — |
| SECONDARY Antibodies to LY2189265 |
9 | — |
Eligibility Criteria
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 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
Data sourced from ClinicalTrials.gov (NCT00734474). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.