Trial Outcomes & Findings for A Study Comparing the Effects and Safety of Dulaglutide With Glimepiride in Type 2 Diabetes Mellitus (NCT NCT01644500)

Last Updated: 2019-09-18

Results Overview

HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) analysis adjusting for treatment, country, pre-study therapy stratum, visit, and treatment-by-visit as fixed effects; baseline HbA1c as covariate; and participant as a random effect.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

737 participants

Primary outcome timeframe

Baseline, 26 Weeks

Results posted on

2019-09-18

Participant Flow

Participant milestones

Participant milestones
Measure	1.5 mg Dulaglutide 1.5 milligrams (mg) dulaglutide administered as one subcutaneous (SC) injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Overall Study STARTED	244	248	245
Overall Study Received at Least One Dose of Study Drug	244	248	243
Overall Study Modified Intent-to-treat Population	239	239	242
Overall Study COMPLETED	222	224	230
Overall Study NOT COMPLETED	22	24	15

Reasons for withdrawal

Reasons for withdrawal
Measure	1.5 mg Dulaglutide 1.5 milligrams (mg) dulaglutide administered as one subcutaneous (SC) injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Overall Study Adverse Event	6	1	2
Overall Study Death	0	1	0
Overall Study Lost to Follow-up	3	8	0
Overall Study Protocol Violation	1	1	0
Overall Study Withdrawal by Subject	11	12	12
Overall Study Physician Decision	1	1	1

Baseline Characteristics

A Study Comparing the Effects and Safety of Dulaglutide With Glimepiride in Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1.5 mg Dulaglutide n=239 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=239 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=242 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.	Total n=720 Participants Total of all reporting groups
Age, Continuous	52.69 years STANDARD_DEVIATION 10.754 • n=5 Participants	53.79 years STANDARD_DEVIATION 10.093 • n=7 Participants	51.97 years STANDARD_DEVIATION 10.052 • n=5 Participants	52.81 years STANDARD_DEVIATION 10.317 • n=4 Participants
Sex: Female, Male Female	105 Participants n=5 Participants	112 Participants n=7 Participants	112 Participants n=5 Participants	329 Participants n=4 Participants
Sex: Female, Male Male	134 Participants n=5 Participants	127 Participants n=7 Participants	130 Participants n=5 Participants	391 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	239 Participants n=5 Participants	239 Participants n=7 Participants	242 Participants n=5 Participants	720 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment Taiwan	29 Participants n=5 Participants	28 Participants n=7 Participants	29 Participants n=5 Participants	86 Participants n=4 Participants
Region of Enrollment China	184 Participants n=5 Participants	186 Participants n=7 Participants	186 Participants n=5 Participants	556 Participants n=4 Participants
Region of Enrollment South Korea	26 Participants n=5 Participants	25 Participants n=7 Participants	27 Participants n=5 Participants	78 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, 26 Weeks

Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, and had at least one post-baseline HbA1c measurement.

Outcome measures

Outcome measures
Measure	1.5 mg Dulaglutide n=239 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=239 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=242 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Change From Baseline in HbA1c at 26 Weeks	-1.48 percentage of HbA1c Standard Error 0.069	-1.22 percentage of HbA1c Standard Error 0.069	-0.92 percentage of HbA1c Standard Error 0.069

SECONDARY outcome

Timeframe: 26 Weeks

Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, and had at least one post-baseline HbA1c measurement. Last observation carried forward (LOCF) methodology was used to impute missing post-baseline values.

Percentages of participants who achieved HbA1c levels of \<7% or ≤6.5% were analyzed using a logistic regression model, controlling for treatment, pre-treatment, baseline HbA1c and country.

Outcome measures

Outcome measures
Measure	1.5 mg Dulaglutide n=239 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=239 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=242 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks HbA1c ≤6.5%	59.4 percentage of participants	47.7 percentage of participants	41.3 percentage of participants
Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks HbA1c <7.0%	74.1 percentage of participants	63.6 percentage of participants	57.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 26 Weeks

Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, and had at least one post-baseline HbA1c measurement.

FBG is a test to determine how much glucose (sugar) is in a blood sample after an overnight fast. FBG was measured by a central laboratory. LS means were calculated using MMRM analysis adjusting for treatment, country, pre-study therapy stratum, visit, and treatment-by-visit as fixed effects; baseline FBG as covariate; and participant as a random effect.

Outcome measures

Outcome measures
Measure	1.5 mg Dulaglutide n=239 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=239 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=242 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks	-2.71 millimoles per liter (mmol/L) Standard Error 0.135	-2.26 millimoles per liter (mmol/L) Standard Error 0.137	-1.89 millimoles per liter (mmol/L) Standard Error 0.136

SECONDARY outcome

Timeframe: Baseline, 26 Weeks

Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, and had at least one post-baseline HbA1c measurement.

Change from baseline in mean daily blood glucose (BG) values were measured with a 7-point SMBG profile. Participants recorded their 7-point SMBG profiles on 2 separate, non-consecutive days during the 2-week period immediately before randomization, Week 8, Week 16, and Week 26 (or the Early Discontinuation Visit). The 7-point SMBG profile consisted of pre-prandial BG measures before the morning (fasting), midday, and evening meals; BG measures 2 hours after the start (post-prandial) of the morning, midday, and evening meals; and BG measures at bedtime. Mean at 26 weeks was assessed in all treatment groups. LS means were calculated using MMRM analysis adjusting for treatment, country, pre-study therapy stratum, visit, and treatment-by-visit as fixed effects; baseline body weight as covariate; and participant as a random effect.

Outcome measures

Outcome measures
Measure	1.5 mg Dulaglutide n=239 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=239 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=242 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks Morning (fasting)	-2.47 mmol/L Standard Error 0.092	-1.91 mmol/L Standard Error 0.092	-1.80 mmol/L Standard Error 0.091
Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks Morning (2 hours post-prandial) meal	-4.56 mmol/L Standard Error 0.180	-3.75 mmol/L Standard Error 0.181	-3.20 mmol/L Standard Error 0.179
Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks Midday (pre-prandial) meal	-3.09 mmol/L Standard Error 0.151	-2.43 mmol/L Standard Error 0.151	-2.37 mmol/L Standard Error 0.150
Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks Midday (2 hours post-prandial) meal	-4.15 mmol/L Standard Error 0.174	-3.40 mmol/L Standard Error 0.174	-2.58 mmol/L Standard Error 0.173
Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks Evening (pre-prandial) meal	-2.36 mmol/L Standard Error 0.135	-1.77 mmol/L Standard Error 0.136	-1.69 mmol/L Standard Error 0.134
Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks Evening (2 hours post-prandial) meal	-3.63 mmol/L Standard Error 0.164	-2.80 mmol/L Standard Error 0.165	-2.35 mmol/L Standard Error 0.164
Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks Bedtime	-3.22 mmol/L Standard Error 0.152	-2.69 mmol/L Standard Error 0.152	-2.03 mmol/L Standard Error 0.150

SECONDARY outcome

Timeframe: Baseline through 26 Weeks

Population: Participants who had been randomized, received at least one dose of study drug, and had evaluable hypoglycemic data.

Hypoglycemic episodes are defined as events that are associated with reported signs and symptoms of hypoglycemia and/or documented BG concentrations of ≤70 milligrams per deciliter (mg/dL) (≤3.9 mmol/L). A severe hypoglycemic episode was defined as any hypoglycemic event for which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Nocturnal hypoglycemia is defined as any hypoglycemic event that occurs between bedtime and waking. Log mean rates of total hypoglycemia (per 30 days per participant) are presented and were calculated from negative binomial regression model. The model included country/region, prior medication group, treatment, visit, and treatment-by-visit interaction. The logarithm of days between visits was adjusted as an offset to account for possible unequal duration between visits and between participants.

Outcome measures

Outcome measures
Measure	1.5 mg Dulaglutide n=244 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=247 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=243 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Rate of Hypoglycemic Episodes All Hypoglycemic Episodes	0.01 episodes/participant/30 days Standard Deviation 0.053	0.01 episodes/participant/30 days Standard Deviation 0.041	0.09 episodes/participant/30 days Standard Deviation 0.581
Rate of Hypoglycemic Episodes Severe Hypoglycemic Episodes	NA episodes/participant/30 days Standard Deviation NA Data not available because no severe hypoglycemic episodes occurred.	NA episodes/participant/30 days Standard Deviation NA Data not available because no severe hypoglycemic episodes occurred.	NA episodes/participant/30 days Standard Deviation NA Data not available because no severe hypoglycemic episodes occurred.
Rate of Hypoglycemic Episodes Nocturnal Hypoglycemic Episodes	0.00 episodes/participant/30 days Standard Deviation 0.011	0.00 episodes/participant/30 days Standard Deviation 0.010	0.01 episodes/participant/30 days Standard Deviation 0.057

SECONDARY outcome

Timeframe: Baseline through 26 Weeks

Population: All participants who were randomized and received at least one dose of study drug.

The overall number of participants with self-reported hypoglycemic episodes is presented.

Outcome measures

Outcome measures
Measure	1.5 mg Dulaglutide n=244 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=248 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=243 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Number of Participants With Self-Reported Hypoglycemic Episodes	14 participants	9 participants	38 participants

SECONDARY outcome

Timeframe: Baseline, up to 26 Weeks

Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, and had at least one post-baseline HbA1c measurement. LOCF methodology was used to impute missing post-baseline values.

Change from baseline in HOMA2-%B was assessed by using the homeostasis model assessment (HOMA) to quantify β-cell function. HOMA2-%B is a computer model that uses FBG, insulin, and C-peptide concentrations to estimate steady state β-cell function (%B) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. LS means were calculated using an analysis of covariance (ANCOVA) model with country, baseline, pre-treatment, and treatment as fixed effects.

Outcome measures

Outcome measures
Measure	1.5 mg Dulaglutide n=239 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=239 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=242 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Change From Baseline in Homeostasis Model Assessment 2 Steady-state Beta (β) - Cell Function (HOMA2-%B) at 26 Weeks Insulin-based HOMA-2%B	47.40 percentage of HOMA2-%B Standard Error 2.624	37.92 percentage of HOMA2-%B Standard Error 2.664	30.00 percentage of HOMA2-%B Standard Error 2.591
Change From Baseline in Homeostasis Model Assessment 2 Steady-state Beta (β) - Cell Function (HOMA2-%B) at 26 Weeks C-peptide HOMA-2%B	41.02 percentage of HOMA2-%B Standard Error 1.945	34.57 percentage of HOMA2-%B Standard Error 1.974	24.58 percentage of HOMA2-%B Standard Error 1.964

SECONDARY outcome

Timeframe: Baseline, up to 26 Weeks

Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, and had at least one post-baseline HbA1c measurement. LOCF methodology was used to impute missing post-baseline values.

Change from baseline in HOMA2-%S was assessed by using the HOMA to quantify insulin sensitivity. HOMA2-%S is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state insulin sensitivity (%S) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. LS means were calculated using an ANCOVA model with country, baseline, pre-treatment, and treatment as fixed effects.

Outcome measures

Outcome measures
Measure	1.5 mg Dulaglutide n=239 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=239 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=242 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Change From Baseline in Homeostasis Model Assessment 2 Insulin Sensitivity - Cell Function (HOMA2-%S) at 26 Weeks Insulin-Based HOMA2-%S	-6.85 percentage of HOMA2-%S Standard Error 2.636	-10.33 percentage of HOMA2-%S Standard Error 2.662	-7.19 percentage of HOMA2-%S Standard Error 2.602
Change From Baseline in Homeostasis Model Assessment 2 Insulin Sensitivity - Cell Function (HOMA2-%S) at 26 Weeks C-Peptide-Based HOMA2-%S	-6.44 percentage of HOMA2-%S Standard Error 2.056	-11.84 percentage of HOMA2-%S Standard Error 2.082	-5.05 percentage of HOMA2-%S Standard Error 2.074

SECONDARY outcome

Timeframe: Baseline, 26 Weeks

Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, had at least one post-baseline HbA1c measurement and had evaluable pancreatic enzyme data.

Amylase (total and pancreas-derived) and lipase concentrations were measured.

Outcome measures

Outcome measures
Measure	1.5 mg Dulaglutide n=239 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=239 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=242 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Change From Baseline in Pancreatic Enzymes at 26 Weeks Total amylase	9.29 units per liter (u/L) Standard Deviation 16.237	7.04 units per liter (u/L) Standard Deviation 13.128	3.79 units per liter (u/L) Standard Deviation 12.538
Change From Baseline in Pancreatic Enzymes at 26 Weeks Pancreas-derived amylase	6.19 units per liter (u/L) Standard Deviation 12.824	4.92 units per liter (u/L) Standard Deviation 8.123	2.64 units per liter (u/L) Standard Deviation 8.218
Change From Baseline in Pancreatic Enzymes at 26 Weeks Lipase	10.62 units per liter (u/L) Standard Deviation 30.086	9.28 units per liter (u/L) Standard Deviation 22.651	2.38 units per liter (u/L) Standard Deviation 22.717

SECONDARY outcome

Timeframe: Baseline, 26 Weeks

Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, had at least one post-baseline HbA1c measurement, and had evaluable serum calcitonin data.

Outcome measures

Outcome measures
Measure	1.5 mg Dulaglutide n=239 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=239 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=242 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Change From Baseline in Serum Calcitonin at 26 Weeks	-0.01 picomoles per liter (pmol/L) Standard Deviation 0.318	-0.02 picomoles per liter (pmol/L) Standard Deviation 0.298	0.02 picomoles per liter (pmol/L) Standard Deviation 1.193

SECONDARY outcome

Timeframe: Baseline, 26 Weeks

Population: All participants who were randomized, received at least one dose of study drug, and had evaluable blood pressure data.

Sitting systolic blood pressure (SBP) and sitting diastolic blood pressure (DBP) were measured. LS means were calculated using MMRM analysis adjusting for treatment, country, pre-study therapy stratum, visit, and treatment-by-visit as fixed effects; baseline blood pressure as covariate; and participant as a random effect.

Outcome measures

Outcome measures
Measure	1.5 mg Dulaglutide n=222 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=224 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=231 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Change From Baseline in Sitting Blood Pressure at 26 Weeks SBP	-2.07 millimeters of mercury (mmHg) Standard Error 0.815	-1.88 millimeters of mercury (mmHg) Standard Error 0.813	-0.66 millimeters of mercury (mmHg) Standard Error 0.804
Change From Baseline in Sitting Blood Pressure at 26 Weeks DBP	-0.10 millimeters of mercury (mmHg) Standard Error 0.535	-0.11 millimeters of mercury (mmHg) Standard Error 0.534	0.15 millimeters of mercury (mmHg) Standard Error 0.526

SECONDARY outcome

Timeframe: Baseline, 26 Weeks

Population: All participants who were randomized, received at least one dose of study drug, and had evaluable pulse rate data.

LS means were calculated using MMRM analysis adjusting for treatment, country, pre-study therapy stratum, visit, and treatment-by-visit as fixed effects; baseline pulse rate as covariate; and participant as a random effect.

Outcome measures

Outcome measures
Measure	1.5 mg Dulaglutide n=222 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=224 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=231 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Change From Baseline in Sitting Pulse Rate at 26 Weeks	3.07 beats per minute (bpm) Standard Error 0.581	1.24 beats per minute (bpm) Standard Error 0.581	-0.34 beats per minute (bpm) Standard Error 0.572

SECONDARY outcome

Timeframe: Baseline, 26 Weeks

The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTcF = QT/RR\^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and R-R wave (RR), which is the interval between two R waves. PR is the interval between the P wave and the ventricular depolarization wave (QRS) complex.

Outcome measures

Outcome measures
Measure	1.5 mg Dulaglutide n=239 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=239 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=242 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Change From Baseline in Electrocardiogram (ECG) Parameters, Fridericia Corrected QT (QTcF) Interval and P-R Wave (PR) Interval at 26 Weeks QT interval	-6.18 milliseconds (msec) Standard Deviation 21.469	-2.06 milliseconds (msec) Standard Deviation 19.549	1.21 milliseconds (msec) Standard Deviation 23.021
Change From Baseline in Electrocardiogram (ECG) Parameters, Fridericia Corrected QT (QTcF) Interval and P-R Wave (PR) Interval at 26 Weeks PR interval	3.73 milliseconds (msec) Standard Deviation 13.411	3.29 milliseconds (msec) Standard Deviation 11.236	-0.23 milliseconds (msec) Standard Deviation 10.184

SECONDARY outcome

Timeframe: Baseline, 26 Weeks

Outcome measures

Outcome measures
Measure	1.5 mg Dulaglutide n=239 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=239 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=242 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Change From Baseline in Heart Rate From ECG at 26 Weeks	3.99 bpm Standard Deviation 8.459	1.90 bpm Standard Deviation 8.046	0.44 bpm Standard Deviation 9.275

SECONDARY outcome

Timeframe: Baseline, 26 Weeks

Population: All participants who were randomized, received at least one dose of study drug, and had evaluable body weight data.

LS means were calculated using MMRM analysis adjusting for treatment, country, pre-study therapy stratum, visit, and treatment-by-visit as fixed effects; baseline body weight as covariate; and participant as a random effect.

Outcome measures

Outcome measures
Measure	1.5 mg Dulaglutide n=222 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=224 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=231 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Change From Baseline in Body Weight at 26 Weeks	-1.46 kilogram (kg) Standard Error 0.192	-0.77 kilogram (kg) Standard Error 0.192	0.89 kilogram (kg) Standard Error 0.190

SECONDARY outcome

Timeframe: Baseline, 26 Weeks

Population: All participants who were randomized, received at least one dose of study drug, and had evaluable BMI data.

BMI is an estimate of body fat based on body weight divided by height squared. LS means were calculated using MMRM analysis adjusting for treatment, country, pre-study therapy stratum, visit, and treatment-by-visit as fixed effects; baseline body weight as covariate; and participant as a random effect.

Outcome measures

Outcome measures
Measure	1.5 mg Dulaglutide n=222 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=223 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=231 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Change From Baseline in Body Mass Index (BMI) at 26 Weeks	-0.55 kilograms per meter squared (kg/m^2) Standard Error 0.070	-0.29 kilograms per meter squared (kg/m^2) Standard Error 0.070	0.32 kilograms per meter squared (kg/m^2) Standard Error 0.069

SECONDARY outcome

Timeframe: Baseline through 26 Weeks

Dulaglutide anti-drug antibodies (ADA) were assessed at baseline and 26 weeks. A participant was considered to have treatment-emergent dulaglutide ADA if the participant had at least 1 titer that was treatment-emergent relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement.

Outcome measures

Outcome measures
Measure	1.5 mg Dulaglutide n=239 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=239 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=242 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Percentage of Participants Developing Antibodies to Dulaglutide	17 percentage of participants	8 percentage of participants	4 percentage of participants

SECONDARY outcome

Timeframe: Baseline through 26 Weeks

Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, and had at least one post-baseline HbA1c measurement.

Deaths and nonfatal cardiovascular adverse events (AEs) were adjudicated by a committee of physicians with cardiology expertise external to the Sponsor. The nonfatal cardiovascular AEs that were adjudicated included myocardial infarction; hospitalization for unstable angina; hospitalization for heart failure; coronary interventions (such as coronary artery bypass graft or percutaneous coronary intervention); and cerebrovascular events, including cerebrovascular accident (stroke) and transient ischemic attack. A summary of serious and other non-serious AEs regardless of causality, is located in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure	1.5 mg Dulaglutide n=239 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=239 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=242 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Number of Participants With Adjudicated Cardiovascular Events	0 number of participants	1 number of participants	0 number of participants

SECONDARY outcome

Timeframe: Baseline through 26 Weeks

Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, and had at least one post-baseline HbA1c measurement.

The number of adjudicated (by an independent committee of expert physicians) pancreatic events is summarized at 26 weeks. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure	1.5 mg Dulaglutide n=239 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=239 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=242 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Number of Participants With Adjudicated Pancreatitis	7 participants	5 participants	1 participants

SECONDARY outcome

Timeframe: Week 26

The EQ-5D questionnaire is a widely used, generic questionnaire that assesses 5 dimensions associated with quality of life (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 3 possible levels of response: no problem, some problem, and extreme problem. Additional categories of response include ambiguous and missing. The number of participants per each of the 5 response categories is summarized for each of the 5 dimensions.

Outcome measures

Outcome measures
Measure	1.5 mg Dulaglutide n=239 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=239 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=242 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Usual activities - ambiguous	0 participants	0 participants	0 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Mobility - no problem	217 participants	218 participants	224 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Mobility - some problem	4 participants	3 participants	6 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Mobility - extreme problem	0 participants	0 participants	0 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Mobility - ambiguous	0 participants	0 participants	0 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Mobility - missing	1 participants	3 participants	1 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Self-care - no problem	221 participants	220 participants	228 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Self-care - some problem	0 participants	1 participants	2 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Self-care - extreme problem	0 participants	0 participants	0 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Self-care - ambiguous	0 participants	0 participants	0 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Self-care - missing	1 participants	3 participants	1 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Usual activities - no problems	221 participants	219 participants	228 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Usual activities - some problems	0 participants	2 participants	2 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Usual activities - extreme problems	0 participants	0 participants	0 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Usual activities - missing	1 participants	3 participants	1 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Pain/Discomfort - no problems	198 participants	192 participants	200 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Pain/Discomfort - some problems	23 participants	28 participants	29 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Pain/Discomfort - extreme problems	0 participants	0 participants	0 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Pain/Discomfort - ambiguous	0 participants	0 participants	0 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Pain/Discomfort - missing	1 participants	3 participants	1 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Anxiety/Depression - no problems	208 participants	214 participants	213 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Anxiety/Depression - some problems	13 participants	7 participants	17 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Anxiety/Depression - extreme problems	0 participants	0 participants	0 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Anxiety/Depression - ambiguous	0 participants	0 participants	0 participants
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks Anxiety/Depression - missing	1 participants	3 participants	1 participants

SECONDARY outcome

Timeframe: Week 26

The EQ-5D questionnaire is a widely used, generic questionnaire that assesses health-related quality of life and consists of a 100-milliliter (mm) visual analog scale (VAS) on which the participant rated their perceived health state on that day from 0-mm (worst imaginable health state) to 100-mm (best imaginable health state).

Outcome measures

Outcome measures
Measure	1.5 mg Dulaglutide n=234 Participants 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=230 Participants 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=237 Participants 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Visual Analog Scale (VAS) Score at 26 Weeks	85.72 units on a scale Standard Deviation 9.723	86.17 units on a scale Standard Deviation 10.744	85.96 units on a scale Standard Deviation 10.938

Adverse Events

1.5 mg Dulaglutide

Serious events: 6 serious events

Other events: 165 other events

Deaths: 0 deaths

0.75 mg Dulaglutide

Serious events: 4 serious events

Other events: 141 other events

Deaths: 0 deaths

Glimepiride

Serious events: 3 serious events

Other events: 137 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	1.5 mg Dulaglutide n=244 participants at risk 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	0.75 mg Dulaglutide n=248 participants at risk 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks.	Glimepiride n=243 participants at risk 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks.
Cardiac disorders Supraventricular tachycardia	0.41% 1/244 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/248 All randomized participants who received at least one dose of study drug.	0.00% 0/243 All randomized participants who received at least one dose of study drug.
Eye disorders Cataract	0.00% 0/244 All randomized participants who received at least one dose of study drug.	0.00% 0/248 All randomized participants who received at least one dose of study drug.	0.41% 1/243 • Number of events 1 All randomized participants who received at least one dose of study drug.
Eye disorders Cataract diabetic	0.00% 0/244 All randomized participants who received at least one dose of study drug.	0.00% 0/248 All randomized participants who received at least one dose of study drug.	0.41% 1/243 • Number of events 1 All randomized participants who received at least one dose of study drug.
Eye disorders Glaucoma	0.00% 0/244 All randomized participants who received at least one dose of study drug.	0.00% 0/248 All randomized participants who received at least one dose of study drug.	0.41% 1/243 • Number of events 1 All randomized participants who received at least one dose of study drug.
Eye disorders Retinal vein occlusion	0.00% 0/244 All randomized participants who received at least one dose of study drug.	0.00% 0/248 All randomized participants who received at least one dose of study drug.	0.41% 1/243 • Number of events 1 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Impaired gastric emptying	0.41% 1/244 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/248 All randomized participants who received at least one dose of study drug.	0.00% 0/243 All randomized participants who received at least one dose of study drug.
Hepatobiliary disorders Cholelithiasis	0.00% 0/244 All randomized participants who received at least one dose of study drug.	0.40% 1/248 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/243 All randomized participants who received at least one dose of study drug.
Infections and infestations Cholecystitis infective	0.00% 0/244 All randomized participants who received at least one dose of study drug.	0.40% 1/248 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/243 All randomized participants who received at least one dose of study drug.
Infections and infestations Pneumonia	0.00% 0/244 All randomized participants who received at least one dose of study drug.	0.00% 0/248 All randomized participants who received at least one dose of study drug.	0.41% 1/243 • Number of events 1 All randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Injury	0.00% 0/244 All randomized participants who received at least one dose of study drug.	0.40% 1/248 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/243 All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Dyslipidaemia	0.00% 0/244 All randomized participants who received at least one dose of study drug.	0.00% 0/248 All randomized participants who received at least one dose of study drug.	0.41% 1/243 • Number of events 1 All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperhomocysteinaemia	0.00% 0/244 All randomized participants who received at least one dose of study drug.	0.00% 0/248 All randomized participants who received at least one dose of study drug.	0.41% 1/243 • Number of events 1 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	0.41% 1/244 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/248 All randomized participants who received at least one dose of study drug.	0.00% 0/243 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Dactylitis	0.00% 0/244 All randomized participants who received at least one dose of study drug.	0.40% 1/248 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/243 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.41% 1/244 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/248 All randomized participants who received at least one dose of study drug.	0.00% 0/243 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.41% 1/244 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/248 All randomized participants who received at least one dose of study drug.	0.00% 0/243 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.82% 2/244 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/248 All randomized participants who received at least one dose of study drug.	0.41% 1/243 • Number of events 1 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Vertebral osteophyte	0.41% 1/244 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/248 All randomized participants who received at least one dose of study drug.	0.00% 0/243 All randomized participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Clear cell renal cell carcinoma	0.41% 1/244 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/248 All randomized participants who received at least one dose of study drug.	0.00% 0/243 All randomized participants who received at least one dose of study drug.
Nervous system disorders Diabetic neuropathy	0.00% 0/244 All randomized participants who received at least one dose of study drug.	0.00% 0/248 All randomized participants who received at least one dose of study drug.	0.41% 1/243 • Number of events 1 All randomized participants who received at least one dose of study drug.
Nervous system disorders Transient ischaemic attack	0.00% 0/244 All randomized participants who received at least one dose of study drug.	0.40% 1/248 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/243 All randomized participants who received at least one dose of study drug.
Renal and urinary disorders Nephrolithiasis	0.41% 1/244 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/248 All randomized participants who received at least one dose of study drug.	0.00% 0/243 All randomized participants who received at least one dose of study drug.
Renal and urinary disorders Renal cyst	0.41% 1/244 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/248 All randomized participants who received at least one dose of study drug.	0.00% 0/243 All randomized participants who received at least one dose of study drug.