Trial Outcomes & Findings for A Study of LY3209590 in Participants With Type 2 Diabetes Mellitus (NCT NCT03736785)

Last Updated: 2021-03-08

Results Overview

HbA1c is the glycosylated fraction of haemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Change from baseline in HbA1c was analysed by mixed model repeated measures (MMRM) including fixed effects of treatment, stratification factors (country, BMI group \[\> 30 or ≤ 30\], sulfonylureas use at study entry), visit and treatment by visit interaction and baseline HbA1c as the covariate.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

399 participants

Primary outcome timeframe

Baseline, Week 32

Results posted on

2021-03-08

Participant Flow

Participant milestones

Participant milestones
Measure	LY3209590 Algorithm 1 Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous (SC) injection. Dose titration was done to maintain fasting blood glucose of \<140 mg/dL.	LY3209590 Algorithm 2 Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous injection. Dose titration was done to maintain fasting blood glucose of \<120 mg/dL.	Insulin Degludec Participants received same dose of Degludec as the total basal insulin dose already administered prior to randomization. Dose was titrated to maintain fasting blood glucose of ≤100 mg/dL to achieve glycemic goal of HbA1C \<7%.
Overall Study STARTED	135	132	132
Overall Study COMPLETED	118	115	118
Overall Study NOT COMPLETED	17	17	14

Reasons for withdrawal

Reasons for withdrawal
Measure	LY3209590 Algorithm 1 Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous (SC) injection. Dose titration was done to maintain fasting blood glucose of \<140 mg/dL.	LY3209590 Algorithm 2 Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous injection. Dose titration was done to maintain fasting blood glucose of \<120 mg/dL.	Insulin Degludec Participants received same dose of Degludec as the total basal insulin dose already administered prior to randomization. Dose was titrated to maintain fasting blood glucose of ≤100 mg/dL to achieve glycemic goal of HbA1C \<7%.
Overall Study Adverse Event	1	1	1
Overall Study Death	1	0	1
Overall Study Lost to Follow-up	0	2	3
Overall Study Non compliance with study drug	1	1	0
Overall Study Physician Decision	0	1	1
Overall Study Protocol Violation	1	4	3
Overall Study Sponsor Decision	1	0	0
Overall Study Unknown/Missing data	3	2	1
Overall Study Withdrawal by Subject	9	6	4

Baseline Characteristics

A Study of LY3209590 in Participants With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LY3209590 Algorithm 1 n=135 Participants Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous (SC) injection. Dose titration was done to maintain fasting blood glucose of \<140 milligram mg.dL	LY3209590 Algorithm 2 n=132 Participants Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous injection. Dose titration was done to maintain fasting blood glucose of \<120 mg/dL.	Insulin Degludec n=132 Participants Participants received same dose of Degludec as the total basal insulin dose already administered prior to randomization. Dose was titrated to maintain fasting blood glucose of ≤100 mg/dL to achieve glycemic goal of HbA1C \<7%.	Total n=399 Participants Total of all reporting groups
Age, Continuous	60.2 years STANDARD_DEVIATION 9.9 • n=5 Participants	59.6 years STANDARD_DEVIATION 11.3 • n=7 Participants	60.8 years STANDARD_DEVIATION 10.0 • n=5 Participants	60.2 years STANDARD_DEVIATION 10.4 • n=4 Participants
Sex: Female, Male Female	67 Participants n=5 Participants	70 Participants n=7 Participants	65 Participants n=5 Participants	202 Participants n=4 Participants
Sex: Female, Male Male	68 Participants n=5 Participants	62 Participants n=7 Participants	67 Participants n=5 Participants	197 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	67 Participants n=5 Participants	78 Participants n=7 Participants	73 Participants n=5 Participants	218 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	68 Participants n=5 Participants	54 Participants n=7 Participants	59 Participants n=5 Participants	181 Participants n=4 Participants
Ethnicity (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
Race (NIH/OMB) American Indian or Alaska Native	16 Participants n=5 Participants	18 Participants n=7 Participants	19 Participants n=5 Participants	53 Participants n=4 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	15 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Black or African American	16 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants	36 Participants n=4 Participants
Race (NIH/OMB) White	97 Participants n=5 Participants	97 Participants n=7 Participants	94 Participants n=5 Participants	288 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment Puerto Rico	18 Participants n=5 Participants	16 Participants n=7 Participants	15 Participants n=5 Participants	49 Participants n=4 Participants
Region of Enrollment United States	96 Participants n=5 Participants	97 Participants n=7 Participants	96 Participants n=5 Participants	289 Participants n=4 Participants
Region of Enrollment Mexico	21 Participants n=5 Participants	19 Participants n=7 Participants	21 Participants n=5 Participants	61 Participants n=4 Participants
Haemoglobin A1c (HbA1c)	8.20 HbA1C percentage (%) STANDARD_DEVIATION 0.87 • n=5 Participants	8.03 HbA1C percentage (%) STANDARD_DEVIATION 0.89 • n=7 Participants	8.13 HbA1C percentage (%) STANDARD_DEVIATION 0.88 • n=5 Participants	8.12 HbA1C percentage (%) STANDARD_DEVIATION 0.88 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Week 32

Population: The data after using rescue medication or stopping study medication were censored. Participants with non-missing baseline value and at least one post baseline value of response were included.

Outcome measures

Outcome measures
Measure	LY3209590 Algorithm 1 n=130 Participants Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous (SC) injection. Dose titration was done to maintain fasting blood glucose of \<140 mg/dL.	LY3209590 Algorithm 2 n=125 Participants Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous injection. Dose titration was done to maintain fasting blood glucose of \<120 mg/dL.	Insulin Degludec n=124 Participants Participants received same dose of Degludec as the total basal insulin dose already administered prior to randomization. Dose was titrated to maintain fasting blood glucose of ≤100 mg/dL to achieve glycemic goal of HbA1C \<7%.
Change From Baseline in HbA1c	-0.58 HbA1C % Standard Error 0.083	-0.57 HbA1C % Standard Error 0.085	-0.66 HbA1C % Standard Error 0.084

SECONDARY outcome

Timeframe: Baseline, Week 32

Population: The data after using rescue medication or stopping study medication were excluded. Participants with non-missing baseline value and at least one post baseline value of response were included.

HbA1c is the glycosylated fraction of haemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Change from baseline in HbA1c was analysed by MMRM including fixed effects of treatment, stratification factors (country, BMI group \[\> 30 or ≤ 30\], sulfonylureas use at study entry), visit and treatment by visit interaction, and baseline HbA1c as the covariate.

Outcome measures

Outcome measures
Measure	LY3209590 Algorithm 1 n=130 Participants Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous (SC) injection. Dose titration was done to maintain fasting blood glucose of \<140 mg/dL.	LY3209590 Algorithm 2 n=125 Participants Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous injection. Dose titration was done to maintain fasting blood glucose of \<120 mg/dL.	Insulin Degludec n=124 Participants Participants received same dose of Degludec as the total basal insulin dose already administered prior to randomization. Dose was titrated to maintain fasting blood glucose of ≤100 mg/dL to achieve glycemic goal of HbA1C \<7%.
Change From Baseline in HbA1c Compared to Insulin Degludec	-0.58 HbA1C % Standard Error 0.083	-0.57 HbA1C % Standard Error 0.085	-0.66 HbA1C % Standard Error 0.084

SECONDARY outcome

Timeframe: Baseline, Week 32

Change from baseline in fasting glucose was analysed by MMRM including fixed effects of treatment, stratification factors (country, BMI group \[\> 30 or ≤ 30\], sulfonylureas use at study entry, HbA1c strata \[\<8.5% or ≥8.5%\]), visit and treatment by visit interaction, and baseline fasting glucose as the covariate.

Outcome measures

Outcome measures
Measure	LY3209590 Algorithm 1 n=130 Participants Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous (SC) injection. Dose titration was done to maintain fasting blood glucose of \<140 mg/dL.	LY3209590 Algorithm 2 n=125 Participants Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous injection. Dose titration was done to maintain fasting blood glucose of \<120 mg/dL.	Insulin Degludec n=124 Participants Participants received same dose of Degludec as the total basal insulin dose already administered prior to randomization. Dose was titrated to maintain fasting blood glucose of ≤100 mg/dL to achieve glycemic goal of HbA1C \<7%.
Change From Baseline in Fasting Glucose	-13.1 Milligram per deicliter (mg/dL) Standard Error 4.01	-18.6 Milligram per deicliter (mg/dL) Standard Error 4.14	-31.5 Milligram per deicliter (mg/dL) Standard Error 4.03

SECONDARY outcome

Timeframe: Week 1, Week 32

Population: Participants with non-missing value at the specified timepoint were included.The data after using rescue medication or stopping study medication were excluded.

The baseline for both LY3209590 arms was the first regular weekly dose at Week 1.

Outcome measures

Outcome measures
Measure	LY3209590 Algorithm 1 n=118 Participants Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous (SC) injection. Dose titration was done to maintain fasting blood glucose of \<140 mg/dL.	LY3209590 Algorithm 2 n=115 Participants Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous injection. Dose titration was done to maintain fasting blood glucose of \<120 mg/dL.	Insulin Degludec Participants received same dose of Degludec as the total basal insulin dose already administered prior to randomization. Dose was titrated to maintain fasting blood glucose of ≤100 mg/dL to achieve glycemic goal of HbA1C \<7%.
Change From Baseline in Insulin Dose (LY3209590)	0.12 Milligrams (mg) Standard Deviation 4.86	0.60 Milligrams (mg) Standard Deviation 3.75	—

SECONDARY outcome

Timeframe: Baseline, Week 32

Population: Participants with non-missing value at the specified timepoint were included.The data after using rescue medication or stopping study medication were excluded.

Change from Baseline in Insulin Dose for Insulin Degludec arm was reported.

Outcome measures

Outcome measures
Measure	LY3209590 Algorithm 1 n=111 Participants Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous (SC) injection. Dose titration was done to maintain fasting blood glucose of \<140 mg/dL.	LY3209590 Algorithm 2 Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous injection. Dose titration was done to maintain fasting blood glucose of \<120 mg/dL.	Insulin Degludec Participants received same dose of Degludec as the total basal insulin dose already administered prior to randomization. Dose was titrated to maintain fasting blood glucose of ≤100 mg/dL to achieve glycemic goal of HbA1C \<7%.
Change From Baseline in Insulin Dose (Insulin Degludec)	16.40 International Units (IU) Standard Deviation 26.06	—	—

SECONDARY outcome

Timeframe: Baseline through week 32

Population: All randomized study participants who received at least one dose of study medication and had evaluable hypoglycaemic data.

The hypoglycemia events were defined by participant reported events with glucose ≤54 mg/dL (3.0 millimole per liter (mmol/L)). Relative Rate was calculated based on Group Mean. Group Mean was estimated by first taking the inverse link function on individual patient covariates, then averaging over all participants.

Outcome measures

Outcome measures
Measure	LY3209590 Algorithm 1 n=135 Participants Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous (SC) injection. Dose titration was done to maintain fasting blood glucose of \<140 mg/dL.	LY3209590 Algorithm 2 n=131 Participants Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous injection. Dose titration was done to maintain fasting blood glucose of \<120 mg/dL.	Insulin Degludec n=132 Participants Participants received same dose of Degludec as the total basal insulin dose already administered prior to randomization. Dose was titrated to maintain fasting blood glucose of ≤100 mg/dL to achieve glycemic goal of HbA1C \<7%.
Rate of Total Documented Symptomatic Hypoglycemia	0.73 Events per participant per year Standard Error 0.119	1.22 Events per participant per year Standard Error 0.378	1.56 Events per participant per year Standard Error 0.375

SECONDARY outcome

Timeframe: Baseline, Week 32

Population: All randomized participants who received at least one dose of study medication and with non-missing baseline value and at least one post baseline value of response were included.

Change from baseline in body weight was analysed by MMRM including fixed effects of treatment, visit and treatment by visit interaction, and baseline body weight as the covariate.

Outcome measures

Outcome measures
Measure	LY3209590 Algorithm 1 n=135 Participants Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous (SC) injection. Dose titration was done to maintain fasting blood glucose of \<140 mg/dL.	LY3209590 Algorithm 2 n=130 Participants Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous injection. Dose titration was done to maintain fasting blood glucose of \<120 mg/dL.	Insulin Degludec n=129 Participants Participants received same dose of Degludec as the total basal insulin dose already administered prior to randomization. Dose was titrated to maintain fasting blood glucose of ≤100 mg/dL to achieve glycemic goal of HbA1C \<7%.
Change From Baseline in Body Weight	1.0 Kilogram (kg) Standard Error 0.33	1.0 Kilogram (kg) Standard Error 0.33	2.0 Kilogram (kg) Standard Error 0.33

SECONDARY outcome

Timeframe: Week 32

Population: All randomized participants who received at least one dose of LY3209590 and had evaluable PK data.

PK: AUC of LY3209590 was reported for LY3209590 Algorithm 1 and LY3209590 Algorithm 2 arms. AUC was calculated for individual participants using the participant's Week 32 LY3209590 dose amount and the participant's estimated clearance value.

Outcome measures

Outcome measures
Measure	LY3209590 Algorithm 1 n=119 Participants Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous (SC) injection. Dose titration was done to maintain fasting blood glucose of \<140 mg/dL.	LY3209590 Algorithm 2 n=112 Participants Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous injection. Dose titration was done to maintain fasting blood glucose of \<120 mg/dL.	Insulin Degludec Participants received same dose of Degludec as the total basal insulin dose already administered prior to randomization. Dose was titrated to maintain fasting blood glucose of ≤100 mg/dL to achieve glycemic goal of HbA1C \<7%.
Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3209590	5360 Nanomole * hour per Liter (nmol * hr/L) Geometric Coefficient of Variation 67	5430 Nanomole * hour per Liter (nmol * hr/L) Geometric Coefficient of Variation 60	—

Adverse Events

LY3209590 Algorithm 1

Serious events: 7 serious events

Other events: 17 other events

Deaths: 1 deaths

LY3209590 Algorithm 2

Serious events: 8 serious events

Other events: 29 other events

Deaths: 0 deaths

Insulin Degludec

Serious events: 10 serious events

Other events: 13 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	LY3209590 Algorithm 1 n=135 participants at risk Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous (SC) injection. Dose titration was done to maintain fasting blood glucose of \<140 mg/dL.	LY3209590 Algorithm 2 n=132 participants at risk Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous injection. Dose titration was done to maintain fasting blood glucose of \<120 mg/dL.	Insulin Degludec n=132 participants at risk Participants received same dose of Degludec as the total basal insulin dose already administered prior to randomization. Dose was titrated to maintain fasting blood glucose of ≤100 mg/dL to achieve glycemic goal of HbA1C \<7%.
Gastrointestinal disorders Diarrhoea	6.7% 9/135 • Number of events 10 • Up to 37 weeks All randomized participants.	6.1% 8/132 • Number of events 9 • Up to 37 weeks All randomized participants.	1.5% 2/132 • Number of events 2 • Up to 37 weeks All randomized participants.
Infections and infestations Upper respiratory tract infection	5.9% 8/135 • Number of events 8 • Up to 37 weeks All randomized participants.	10.6% 14/132 • Number of events 14 • Up to 37 weeks All randomized participants.	4.5% 6/132 • Number of events 6 • Up to 37 weeks All randomized participants.
Nervous system disorders Dizziness	0.74% 1/135 • Number of events 1 • Up to 37 weeks All randomized participants.	5.3% 7/132 • Number of events 7 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.
Respiratory, thoracic and mediastinal disorders Cough	0.74% 1/135 • Number of events 1 • Up to 37 weeks All randomized participants.	3.8% 5/132 • Number of events 5 • Up to 37 weeks All randomized participants.	5.3% 7/132 • Number of events 8 • Up to 37 weeks All randomized participants.

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	LY3209590 Algorithm 1 n=135 participants at risk Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous (SC) injection. Dose titration was done to maintain fasting blood glucose of \<140 mg/dL.	LY3209590 Algorithm 2 n=132 participants at risk Participants received loading dose followed by weekly dose of LY3209590 based on the prior randomization basal insulin dose for a period of 32 weeks by subcutaneous injection. Dose titration was done to maintain fasting blood glucose of \<120 mg/dL.	Insulin Degludec n=132 participants at risk Participants received same dose of Degludec as the total basal insulin dose already administered prior to randomization. Dose was titrated to maintain fasting blood glucose of ≤100 mg/dL to achieve glycemic goal of HbA1C \<7%.
Cardiac disorders Acute myocardial infarction	0.00% 0/135 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.
Gastrointestinal disorders Chronic gastritis	0.00% 0/135 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.
Gastrointestinal disorders Nausea	0.00% 0/135 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/135 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.
Gastrointestinal disorders Vomiting	0.00% 0/135 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.
General disorders Chest pain	0.74% 1/135 • Number of events 1 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 2 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.
General disorders Non-cardiac chest pain	0.00% 0/135 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.
General disorders Sudden cardiac death	0.00% 0/135 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.
Hepatobiliary disorders Cholelithiasis	0.00% 0/135 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.
Infections and infestations Abscess limb	0.74% 1/135 • Number of events 1 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.
Infections and infestations Cellulitis	0.74% 1/135 • Number of events 1 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.
Infections and infestations Meningitis viral	0.00% 0/135 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.
Infections and infestations Osteomyelitis	0.74% 1/135 • Number of events 1 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.
Infections and infestations Pneumonia	0.00% 0/135 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.
Infections and infestations Psoas abscess	0.00% 0/135 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.
Infections and infestations Sepsis	0.00% 0/135 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/135 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.
Metabolism and nutrition disorders Dehydration	0.00% 0/135 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/135 • Up to 37 weeks All randomized participants.	1.5% 2/132 • Number of events 2 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/135 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/135 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic neoplasm	0.74% 1/135 • Number of events 1 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.74% 1/135 • Number of events 1 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.
Nervous system disorders Ischaemic stroke	0.00% 0/135 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.
Nervous system disorders Syncope	0.00% 0/135 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.
Psychiatric disorders Mental status changes	0.00% 0/135 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/135 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.
Skin and subcutaneous tissue disorders Diabetic foot	0.74% 1/135 • Number of events 1 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.
Vascular disorders Arteriosclerosis	0.74% 1/135 • Number of events 1 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.
Vascular disorders Hypertensive emergency	0.00% 0/135 • Up to 37 weeks All randomized participants.	0.76% 1/132 • Number of events 1 • Up to 37 weeks All randomized participants.	0.00% 0/132 • Up to 37 weeks All randomized participants.