Trial Outcomes & Findings for A Study of Investigational Dulaglutide Doses in Participants With Type 2 Diabetes on Metformin Monotherapy (NCT NCT02973100)

Last Updated: 2019-09-23

Results Overview

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with baseline as a covariate, pooled country, treatment, time, treatment\*time as fixed effects.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

318 participants

Primary outcome timeframe

Baseline, Week 18

Results posted on

2019-09-23

Participant Flow

The study consisted of 3 periods: an approximately 2-week lead-in period, followed by an 18-week treatment period, and a 4-week safety follow-up period.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo once weekly (QW) by subcutaneous (SC) injection.	Dulaglutide 1.5 Milligrams (mg) Participants received 1.5mg of dulaglutide QW by SC injection.	Dulaglutide 3.0mg Participants received 3.0mg of dulaglutide QW by SC injection.	Dulaglutide 4.5mg Participants received 4.5mg of dulaglutide QW by SC injection.
Overall Study STARTED	82	81	79	76
Overall Study Received at Least 1 Dose of Study Drug	81	81	79	76
Overall Study COMPLETED	75	73	75	69
Overall Study NOT COMPLETED	7	8	4	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo once weekly (QW) by subcutaneous (SC) injection.	Dulaglutide 1.5 Milligrams (mg) Participants received 1.5mg of dulaglutide QW by SC injection.	Dulaglutide 3.0mg Participants received 3.0mg of dulaglutide QW by SC injection.	Dulaglutide 4.5mg Participants received 4.5mg of dulaglutide QW by SC injection.
Overall Study Adverse Event	1	2	1	2
Overall Study Lost to Follow-up	3	1	1	0
Overall Study Withdrawal by Subject	3	5	1	4
Overall Study Notification of change in address	0	0	0	1
Overall Study Failed to attend Safety followup period	0	0	1	0

Baseline Characteristics

A Study of Investigational Dulaglutide Doses in Participants With Type 2 Diabetes on Metformin Monotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=81 Participants Participants received placebo once weekly (QW) by subcutaneous (SC) injection.	Dulaglutide 1.5mg n=81 Participants Participants received 1.5mg of dulaglutide QW by SC injection.	Dulaglutide 3.0mg n=79 Participants Participants received 3.0mg of dulaglutide QW by SC injection.	Dulaglutide 4.5mg n=76 Participants Participants received 4.5mg of dulaglutide QW by SC injection.	Total n=317 Participants Total of all reporting groups
Age, Continuous	56.52 Years STANDARD_DEVIATION 8.93 • n=5 Participants	57.65 Years STANDARD_DEVIATION 9.79 • n=7 Participants	55.90 Years STANDARD_DEVIATION 10.74 • n=5 Participants	57.13 Years STANDARD_DEVIATION 9.63 • n=4 Participants	56.80 Years STANDARD_DEVIATION 9.77 • n=21 Participants
Sex: Female, Male Female	33 Participants n=5 Participants	42 Participants n=7 Participants	44 Participants n=5 Participants	40 Participants n=4 Participants	159 Participants n=21 Participants
Sex: Female, Male Male	48 Participants n=5 Participants	39 Participants n=7 Participants	35 Participants n=5 Participants	36 Participants n=4 Participants	158 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	35 Participants n=5 Participants	32 Participants n=7 Participants	38 Participants n=5 Participants	30 Participants n=4 Participants	135 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	46 Participants n=5 Participants	49 Participants n=7 Participants	40 Participants n=5 Participants	45 Participants n=4 Participants	180 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	10 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants	6 Participants n=4 Participants	31 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	4 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	24 Participants n=21 Participants
Race (NIH/OMB) White	59 Participants n=5 Participants	68 Participants n=7 Participants	58 Participants n=5 Participants	59 Participants n=4 Participants	244 Participants n=21 Participants
Race (NIH/OMB) More than one race	5 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	12 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Region of Enrollment Romania	6 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	21 Participants n=21 Participants
Region of Enrollment United States	42 Participants n=5 Participants	45 Participants n=7 Participants	44 Participants n=5 Participants	43 Participants n=4 Participants	174 Participants n=21 Participants
Region of Enrollment Czechia	10 Participants n=5 Participants	9 Participants n=7 Participants	10 Participants n=5 Participants	8 Participants n=4 Participants	37 Participants n=21 Participants
Region of Enrollment Poland	13 Participants n=5 Participants	11 Participants n=7 Participants	10 Participants n=5 Participants	10 Participants n=4 Participants	44 Participants n=21 Participants
Region of Enrollment Mexico	10 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants	11 Participants n=4 Participants	41 Participants n=21 Participants
Baseline Hemoglobin A1c (HbA1c)	8.08 Percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.79 • n=5 Participants	8.02 Percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.80 • n=7 Participants	8.16 Percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.92 • n=5 Participants	8.12 Percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.81 • n=4 Participants	8.09 Percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.83 • n=21 Participants

PRIMARY outcome

Timeframe: Baseline, Week 18

Population: All randomized participants who received at least one dose of study drug and had postbaseline values, excluding post rescue data for Hemoglobin A1c.

Outcome measures

Outcome measures
Measure	Placebo n=70 Participants Participants received placebo once weekly (QW) by subcutaneous (SC) injection.	Dulaglutide 1.5mg n=73 Participants Participants received 1.5mg of dulaglutide QW by SC injection.	Dulaglutide 3.0mg n=73 Participants Participants received 3.0mg of dulaglutide QW by SC injection.	Dulaglutide 4.5mg n=66 Participants Participants received 4.5mg of dulaglutide QW by SC injection.
Change From Baseline in Hemoglobin A1c (HbA1c)	-0.44 Percentage of glycosylated hemoglobin Standard Error 0.101	-1.23 Percentage of glycosylated hemoglobin Standard Error 0.099	-1.31 Percentage of glycosylated hemoglobin Standard Error 0.099	-1.40 Percentage of glycosylated hemoglobin Standard Error 0.103

SECONDARY outcome

Timeframe: Week 18

Population: All randomized participants who received at least one dose of study drug and had postbaseline values, excluding post rescue data for Hemoglobin A1c.

Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

Outcome measures

Outcome measures
Measure	Placebo n=70 Participants Participants received placebo once weekly (QW) by subcutaneous (SC) injection.	Dulaglutide 1.5mg n=73 Participants Participants received 1.5mg of dulaglutide QW by SC injection.	Dulaglutide 3.0mg n=73 Participants Participants received 3.0mg of dulaglutide QW by SC injection.	Dulaglutide 4.5mg n=66 Participants Participants received 4.5mg of dulaglutide QW by SC injection.
Percentage of Participants With HbA1c of <7.0%	20 Percentage of Participants	71.2 Percentage of Participants	71.2 Percentage of Participants	68.2 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Week 18

Population: All randomized participants who received at least one dose of study drug and had postbaseline values, excluding post rescue data for FSG.

Fasting serum glucose (FSG) is a test to determine how much glucose (sugar) is in a serum sample after an overnight fast. Least Squares (LS) means was determined by MMRM methodology with baseline as a covariate, pooled country, baseline HbA1c strata using \>=8% as cutoff, treatment, time, treatment\*time as fixed effects.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Participants received placebo once weekly (QW) by subcutaneous (SC) injection.	Dulaglutide 1.5mg n=62 Participants Participants received 1.5mg of dulaglutide QW by SC injection.	Dulaglutide 3.0mg n=67 Participants Participants received 3.0mg of dulaglutide QW by SC injection.	Dulaglutide 4.5mg n=61 Participants Participants received 4.5mg of dulaglutide QW by SC injection.
Change From Baseline in Fasting Serum Glucose (FSG)	-0.69 millimole/liter (mmol/L) Standard Error 0.257	-2.01 millimole/liter (mmol/L) Standard Error 0.261	-1.92 millimole/liter (mmol/L) Standard Error 0.250	-2.11 millimole/liter (mmol/L) Standard Error 0.263

SECONDARY outcome

Timeframe: Baseline, Week 18

Population: All randomized participants who received at least one dose of study drug and had postbaseline values, excluding post rescue data for body weight.

Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with baseline as a covariate, pooled country, baseline HbA1c strata using \>=8% as cutoff, treatment, time, treatment\*time as fixed effects.

Outcome measures

Outcome measures
Measure	Placebo n=70 Participants Participants received placebo once weekly (QW) by subcutaneous (SC) injection.	Dulaglutide 1.5mg n=72 Participants Participants received 1.5mg of dulaglutide QW by SC injection.	Dulaglutide 3.0mg n=74 Participants Participants received 3.0mg of dulaglutide QW by SC injection.	Dulaglutide 4.5mg n=67 Participants Participants received 4.5mg of dulaglutide QW by SC injection.
Change From Baseline in Body Weight	-1.6 Kilograms (Kg) Standard Error 0.39	-2.8 Kilograms (Kg) Standard Error 0.39	-3.9 Kilograms (Kg) Standard Error 0.39	-4.1 Kilograms (Kg) Standard Error 0.41

SECONDARY outcome

Timeframe: Baseline through Week 18

Population: All randomized participants who received study drug and had postbaseline data for safety analyses.

Adverse event (AE) defined as any unfavorable medical event, newly emerged or a deterioration of a preexisting condition, in other words any untoward medical occurrence in a patient administered a pharmaceutical product, without regard to the possibility of a causal relationship, that occurred after the visit for informed consent and up to the visit for completion of administration, or discontinuation.

Outcome measures

Outcome measures
Measure	Placebo n=82 Participants Participants received placebo once weekly (QW) by subcutaneous (SC) injection.	Dulaglutide 1.5mg n=81 Participants Participants received 1.5mg of dulaglutide QW by SC injection.	Dulaglutide 3.0mg n=79 Participants Participants received 3.0mg of dulaglutide QW by SC injection.	Dulaglutide 4.5mg n=76 Participants Participants received 4.5mg of dulaglutide QW by SC injection.
Percentage of Participants Discontinuing Study Drug Due to Adverse Events	4.9 Percentage of Participants	6.2 Percentage of Participants	10.1 Percentage of Participants	13.2 Percentage of Participants

SECONDARY outcome

Timeframe: Week 18

Population: All randomized participants who received at least one dose of study drug and had postbaseline values, excluding post rescue values for hypoglycemic episodes.

Hypoglycemic events (HE) were classified as severe, documented symptomatic (defined as an HE with typical symptoms of hypoglycemia and a blood glucose level of ≤3.9 millimoles per liter \[mmol/L\]). Hypoglycemia rate per 30 days was summarized at each visit by treatment group. The rate of hypoglycemia was analyzed using a generalized estimation equations model with a negative binomial distribution and a Log link. LS mean was determined by MMRM methodology with baseline hypoglycemia rate, pooled country, HbA1c at Baseline, treatment, with log of exposure in days divided by 365.25 as the offset.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants Participants received placebo once weekly (QW) by subcutaneous (SC) injection.	Dulaglutide 1.5mg n=81 Participants Participants received 1.5mg of dulaglutide QW by SC injection.	Dulaglutide 3.0mg n=79 Participants Participants received 3.0mg of dulaglutide QW by SC injection.	Dulaglutide 4.5mg n=76 Participants Participants received 4.5mg of dulaglutide QW by SC injection.
Rate of Documented Symptomatic Hypoglycemia	0.00 Episodes/participant/365.25 days Standard Error 0.000	0.00 Episodes/participant/365.25 days Standard Error 0.000	0.00 Episodes/participant/365.25 days Standard Error 0.000	0.00 Episodes/participant/365.25 days Standard Error 0.001

SECONDARY outcome

Timeframe: 0, 2, 4, 6, 10, 18, 22 weeks and early termination

Population: All randomized participants who received at least one dose of the study drug and have evaluable PK data.

Plasma samples for PK analysis were combined measure obtained from 0, 2, 4, 6, 10, 18, 22 weeks and until early termination of the visit. Cmax takes all time points post dose into account and one value was reported.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants Participants received placebo once weekly (QW) by subcutaneous (SC) injection.	Dulaglutide 1.5mg n=79 Participants Participants received 1.5mg of dulaglutide QW by SC injection.	Dulaglutide 3.0mg n=76 Participants Participants received 3.0mg of dulaglutide QW by SC injection.	Dulaglutide 4.5mg Participants received 4.5mg of dulaglutide QW by SC injection.
Pharmacokinetics (PK): The Maximum Drug Concentration at Steady State (Cmax,ss) of Dulaglutide	90.4 nanogram per milliliter (ng/mL) Interval 38.9 to 170.0	151 nanogram per milliliter (ng/mL) Interval 64.3 to 277.0	204 nanogram per milliliter (ng/mL) Interval 87.2 to 377.0	—

SECONDARY outcome

Timeframe: 0, 2, 4, 6, 10, 18, 22 weeks and early termination

Population: All randomized participants who received at least one dose of the study drug and have evaluable PK data.

AUC\[0-168h\] is a combined measure obtained from 0, 2, 4, 6, 10, 18, 22 weeks and until early termination of the visit.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants Participants received placebo once weekly (QW) by subcutaneous (SC) injection.	Dulaglutide 1.5mg n=79 Participants Participants received 1.5mg of dulaglutide QW by SC injection.	Dulaglutide 3.0mg n=76 Participants Participants received 3.0mg of dulaglutide QW by SC injection.	Dulaglutide 4.5mg Participants received 4.5mg of dulaglutide QW by SC injection.
Pharmacokinetics: Area Under the Concentration-Time Curve at Steady State From Time Zero to 168 Hours (AUC[0-168], ss) of Dulaglutide	11800 nanogramhour per milliliter (ngh/mL) Interval 5300.0 to 21300.0	26700 nanogramhour per milliliter (ngh/mL) Interval 15300.0 to 41400.0	36600 nanogramhour per milliliter (ngh/mL) Interval 21100.0 to 56500.0	—

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 29 other events

Deaths: 0 deaths

Dulaglutide 1.5mg

Serious events: 3 serious events

Other events: 36 other events

Deaths: 0 deaths

Dulaglutide 3.0mg

Serious events: 7 serious events

Other events: 49 other events

Deaths: 0 deaths

Dulaglutide 4.5mg

Serious events: 3 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Placebo n=81 participants at risk Participants received placebo once weekly (QW) by subcutaneous (SC) injection.	Dulaglutide 1.5mg n=81 participants at risk Participants received 1.5mg of dulaglutide QW by SC injection.	Dulaglutide 3.0mg n=79 participants at risk Participants received 3.0mg of dulaglutide QW by SC injection.	Dulaglutide 4.5mg n=76 participants at risk Participants received 4.5mg of dulaglutide QW by SC injection.
Cardiac disorders Acute myocardial infarction	1.2% 1/81 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/79 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/76 • Up to 22 weeks All participants who received at least one dose of study drug.
Cardiac disorders Atrioventricular block second degree	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/79 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/76 • Up to 22 weeks All participants who received at least one dose of study drug.
Cardiac disorders Myocardial infarction	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	1.2% 1/81 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/79 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/76 • Up to 22 weeks All participants who received at least one dose of study drug.
Cardiac disorders Pericarditis	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	1.2% 1/81 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/79 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/76 • Up to 22 weeks All participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/79 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/76 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.
Gastrointestinal disorders Pancreatitis	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/79 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/76 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/79 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/76 • Up to 22 weeks All participants who received at least one dose of study drug.
Hepatobiliary disorders Cholecystitis	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/79 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/76 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/79 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/76 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.
Hepatobiliary disorders Cholelithiasis	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	1.2% 1/81 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/79 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/76 • Up to 22 weeks All participants who received at least one dose of study drug.
Infections and infestations Bronchitis	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/79 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/76 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.
Infections and infestations Cholecystitis infective	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/79 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/76 • Up to 22 weeks All participants who received at least one dose of study drug.
Infections and infestations Fungal oesophagitis	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/79 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/76 • Up to 22 weeks All participants who received at least one dose of study drug.
Infections and infestations Peritonsillar abscess	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/79 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/76 • Up to 22 weeks All participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Traumatic intracranial haemorrhage	1.2% 1/81 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/79 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/76 • Up to 22 weeks All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperglycaemic hyperosmolar nonketotic syndrome	1.2% 1/81 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/79 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/76 • Up to 22 weeks All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/79 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/76 • Up to 22 weeks All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypovolaemia	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/79 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/76 • Up to 22 weeks All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Spinal pain	1.2% 1/81 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/79 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/76 • Up to 22 weeks All participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/79 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/76 • Up to 22 weeks All participants who received at least one dose of study drug.
Renal and urinary disorders Renal failure	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/79 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/76 • Up to 22 weeks All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/79 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/76 • Up to 22 weeks All participants who received at least one dose of study drug.
Vascular disorders Hypotension	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/79 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/76 • Up to 22 weeks All participants who received at least one dose of study drug.

Measure	Placebo n=81 participants at risk Participants received placebo once weekly (QW) by subcutaneous (SC) injection.	Dulaglutide 1.5mg n=81 participants at risk Participants received 1.5mg of dulaglutide QW by SC injection.	Dulaglutide 3.0mg n=79 participants at risk Participants received 3.0mg of dulaglutide QW by SC injection.	Dulaglutide 4.5mg n=76 participants at risk Participants received 4.5mg of dulaglutide QW by SC injection.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	2.5% 2/79 • Number of events 2 • Up to 22 weeks All participants who received at least one dose of study drug.	5.3% 4/76 • Number of events 10 • Up to 22 weeks All participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	1.2% 1/81 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	3.7% 3/81 • Number of events 4 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/79 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	9.2% 7/76 • Number of events 7 • Up to 22 weeks All participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	6.2% 5/81 • Number of events 5 • Up to 22 weeks All participants who received at least one dose of study drug.	5.1% 4/79 • Number of events 4 • Up to 22 weeks All participants who received at least one dose of study drug.	7.9% 6/76 • Number of events 6 • Up to 22 weeks All participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	11.1% 9/81 • Number of events 10 • Up to 22 weeks All participants who received at least one dose of study drug.	11.1% 9/81 • Number of events 17 • Up to 22 weeks All participants who received at least one dose of study drug.	22.8% 18/79 • Number of events 34 • Up to 22 weeks All participants who received at least one dose of study drug.	21.1% 16/76 • Number of events 32 • Up to 22 weeks All participants who received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	7.4% 6/81 • Number of events 10 • Up to 22 weeks All participants who received at least one dose of study drug.	6.3% 5/79 • Number of events 5 • Up to 22 weeks All participants who received at least one dose of study drug.	10.5% 8/76 • Number of events 13 • Up to 22 weeks All participants who received at least one dose of study drug.
Gastrointestinal disorders Eructation	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	3.7% 3/81 • Number of events 3 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/79 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	7.9% 6/76 • Number of events 6 • Up to 22 weeks All participants who received at least one dose of study drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	6.2% 5/81 • Number of events 5 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/79 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/76 • Up to 22 weeks All participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	4.9% 4/81 • Number of events 5 • Up to 22 weeks All participants who received at least one dose of study drug.	22.2% 18/81 • Number of events 45 • Up to 22 weeks All participants who received at least one dose of study drug.	25.3% 20/79 • Number of events 32 • Up to 22 weeks All participants who received at least one dose of study drug.	30.3% 23/76 • Number of events 40 • Up to 22 weeks All participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	4.9% 4/81 • Number of events 6 • Up to 22 weeks All participants who received at least one dose of study drug.	11.1% 9/81 • Number of events 20 • Up to 22 weeks All participants who received at least one dose of study drug.	11.4% 9/79 • Number of events 15 • Up to 22 weeks All participants who received at least one dose of study drug.	13.2% 10/76 • Number of events 16 • Up to 22 weeks All participants who received at least one dose of study drug.
General disorders Fatigue	2.5% 2/81 • Number of events 3 • Up to 22 weeks All participants who received at least one dose of study drug.	1.2% 1/81 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	5.1% 4/79 • Number of events 4 • Up to 22 weeks All participants who received at least one dose of study drug.	9.2% 7/76 • Number of events 7 • Up to 22 weeks All participants who received at least one dose of study drug.
Infections and infestations Influenza	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	1.2% 1/81 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	5.1% 4/79 • Number of events 4 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/76 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	3.7% 3/81 • Number of events 5 • Up to 22 weeks All participants who received at least one dose of study drug.	1.2% 1/81 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	6.3% 5/79 • Number of events 5 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/76 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.
Infections and infestations Viral upper respiratory tract infection	6.2% 5/81 • Number of events 7 • Up to 22 weeks All participants who received at least one dose of study drug.	2.5% 2/81 • Number of events 2 • Up to 22 weeks All participants who received at least one dose of study drug.	7.6% 6/79 • Number of events 6 • Up to 22 weeks All participants who received at least one dose of study drug.	3.9% 3/76 • Number of events 4 • Up to 22 weeks All participants who received at least one dose of study drug.
Investigations Weight decreased	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	3.7% 3/81 • Number of events 6 • Up to 22 weeks All participants who received at least one dose of study drug.	6.3% 5/79 • Number of events 6 • Up to 22 weeks All participants who received at least one dose of study drug.	2.6% 2/76 • Number of events 2 • Up to 22 weeks All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	1.2% 1/81 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	3.7% 3/81 • Number of events 3 • Up to 22 weeks All participants who received at least one dose of study drug.	16.5% 13/79 • Number of events 17 • Up to 22 weeks All participants who received at least one dose of study drug.	7.9% 6/76 • Number of events 6 • Up to 22 weeks All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	1.2% 1/81 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/81 • Up to 22 weeks All participants who received at least one dose of study drug.	1.3% 1/79 • Number of events 2 • Up to 22 weeks All participants who received at least one dose of study drug.	5.3% 4/76 • Number of events 4 • Up to 22 weeks All participants who received at least one dose of study drug.
Nervous system disorders Dizziness	4.9% 4/81 • Number of events 6 • Up to 22 weeks All participants who received at least one dose of study drug.	4.9% 4/81 • Number of events 6 • Up to 22 weeks All participants who received at least one dose of study drug.	6.3% 5/79 • Number of events 6 • Up to 22 weeks All participants who received at least one dose of study drug.	5.3% 4/76 • Number of events 5 • Up to 22 weeks All participants who received at least one dose of study drug.
Nervous system disorders Headache	8.6% 7/81 • Number of events 11 • Up to 22 weeks All participants who received at least one dose of study drug.	4.9% 4/81 • Number of events 4 • Up to 22 weeks All participants who received at least one dose of study drug.	12.7% 10/79 • Number of events 13 • Up to 22 weeks All participants who received at least one dose of study drug.	6.6% 5/76 • Number of events 8 • Up to 22 weeks All participants who received at least one dose of study drug.
Vascular disorders Hypertension	1.2% 1/81 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	1.2% 1/81 • Number of events 1 • Up to 22 weeks All participants who received at least one dose of study drug.	5.1% 4/79 • Number of events 4 • Up to 22 weeks All participants who received at least one dose of study drug.	0.00% 0/76 • Up to 22 weeks All participants who received at least one dose of study drug.