A Study of LY3209590 in Participants With Type 2 Diabetes Mellitus

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03736785
• Collaborator: (none)
• Enrollment: 399
• Locations: 44
• Arms: 3
• Actual Duration (Months): 15.1
• Patients Per Site: 9.1
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The reason for this study is to see if the study drug LY3209590 is safe and effective in participants with type 2 diabetes that have already been treated with basal insulin.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: LY3209590; Drug: Insulin Degludec	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 399 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Open-Label Trial to Evaluate the Safety and Efficacy of LY3209590 in Study Participants With Type 2 Diabetes Mellitus Previously Treated With Basal Insulin
• Actual Study Start Date: Nov 15, 2018
• Actual Primary Completion Date: Feb 18, 2020
• Actual Study Completion Date: Feb 18, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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 milligram per deciliter (mg/dL).	Drug: LY3209590; Administered SC
Experimental: 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.	Drug: LY3209590; Administered SC
Active Comparator: 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%.	Drug: Insulin Degludec; Administered SC

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in HbA1c [Baseline, Week 32]

   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.

Secondary Outcome Measures

1. Change From Baseline in HbA1c Compared to Insulin Degludec [Baseline, Week 32]

   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.

2. Change From Baseline in Fasting Glucose [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.

3. Change From Baseline in Insulin Dose (LY3209590) [Week 1, Week 32]

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

4. Change From Baseline in Insulin Dose (Insulin Degludec) [Baseline, Week 32]

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

5. Rate of Total Documented Symptomatic Hypoglycemia [Baseline through week 32]

   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.

6. Change From Baseline in Body Weight [Baseline, Week 32]

   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.

7. Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3209590 [Week 32]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type 2 diabetes mellitus according to the World Health Organization (WHO) criteria treated with basal insulin and up to 3 of the following oral antihyperglycemic medication (OAM):

• dipeptidyl peptidase-4 (DPP-4) inhibitors

• sodium-glucose cotransporter (SGLT-2) inhibitors

• biguanides

• alpha-glucosidase inhibitors

• sulfonlyureas

• HbA1c value of 6.5% to 10%, inclusive

• Body mass index (BMI) between 20 and 45 kilograms per meter squared (kg/m2), inclusive

Exclusion Criteria:

• Type 1 diabetes mellitus or latent autoimmune diabetes

• Any episodes of severe hypoglycemia and/or hypoglycemia unawareness within the 6 months prior to screening

• Any of the following cardiovascular (CV) conditions: acute myocardial infarction, New York Heart Association Class III or IV heart failure, or cerebrovascular accident (stroke)

• Acute or chronic hepatitis, or obvious clinical signs or symptoms of any other liver disease

• Estimated glomerular filtration rate (eGFR) <30 milliliters/minute/1.73 m2

• Active or untreated malignancy

• Chronic (>14 days) systemic glucocorticoid therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Central Research Associates, Inc.	Birmingham	Alabama	United States	35205
2	Arkansas Clinical Research	Little Rock	Arkansas	United States	72205
3	John Muir Physician Network Clinical Research Center	Concord	California	United States	94520
4	AMCR Institute INC	Escondido	California	United States	92025
5	Valley Endocrine, Fresno	Fresno	California	United States	93720
6	Marin Endocrine Associates	Greenbrae	California	United States	94904
7	National Research Institute	Huntington Park	California	United States	90255
8	First Valley Medical Group	Lancaster	California	United States	93534
9	National Research Institute	Los Angeles	California	United States	90057
10	University Clinical Investigators, Inc.	Tustin	California	United States	92780
11	Chase Medical Research, LLC	Waterbury	Connecticut	United States	06708
12	ALL Medical Research, LLC	Cooper City	Florida	United States	33024
13	Suncoast Clinical Research	New Port Richey	Florida	United States	34652
14	Metabolic Research Institute Inc.	West Palm Beach	Florida	United States	33401
15	East West Medical Institute	Honolulu	Hawaii	United States	96814
16	Elite Clinical Trials LLLP	Blackfoot	Idaho	United States	83221
17	Rocky Mountain Diabetes and Osteoporosis Center	Idaho Falls	Idaho	United States	83404
18	Iderc, P.L.C.	West Des Moines	Iowa	United States	50265
19	Cotton O'Neil Diabetes and Endocrinology Center	Topeka	Kansas	United States	66606
20	Endocrine and Metabolic Consultants	Rockville	Maryland	United States	20852
21	NECCR PrimaCare Research, LLC	Fall River	Massachusetts	United States	02721
22	Palm Research Center	Las Vegas	Nevada	United States	89128
23	Palm Research Center	Las Vegas	Nevada	United States	89148
24	Southern New Hampshire Diabetes and Endocrinology	Nashua	New Hampshire	United States	03063
25	Metrolina Internal Medicine, P.A.	Charlotte	North Carolina	United States	28207
26	Intend Research	Norman	Oklahoma	United States	73069
27	The Corvallis Clinic P.C.	Corvallis	Oregon	United States	97330
28	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
29	Preferred Primary Care Physicians - Jacob Murphy Lane	Uniontown	Pennsylvania	United States	15401
30	Internal Medicine Associates of Anderson	Anderson	South Carolina	United States	29621
31	The Research Center of the Upstate	Mauldin	South Carolina	United States	29662
32	Texas Diabetes and Endocrinology	Austin	Texas	United States	78731-4309
33	Dallas Diabetes Endocrine Center	Dallas	Texas	United States	75230
34	Clinical Trials of Texas, Inc.	San Antonio	Texas	United States	78229
35	Manassas Clinical Research Center	Manassas	Virginia	United States	20110
36	Rainier Clinical Research Center	Renton	Washington	United States	98057
37	Confluence Health Clinical Research Department	Wenatchee	Washington	United States	98801
38	Hospital Universitario UANL	Monterrey	Nuevo León	Mexico	64460
39	Investigacion en Salud y Metabolismo S.C	Chihuahua		Mexico	31217
40	Advanced Clinical Research, LLC	Bayamon		Puerto Rico	00961
41	Manati Center for Clinical Research Inc	Manati		Puerto Rico	00674
42	GCM Medical Group PSC	San Juan		Puerto Rico	00917
43	Martha Gomez Cuellar M.D.	San Juan		Puerto Rico	00921
44	Centro de Endocrinologia del Este	Yabucoa		Puerto Rico	00767

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

• Study Protocol - Aug 31, 2018
• Statistical Analysis Plan - Mar 16, 2020

More Information

Additional Information:

• A Study of LY3209590 in Participants With Type 2 Diabetes Mellitus

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03736785
• Other Study ID Numbers: 17059; I8H-MC-BDCM
• First Posted: Nov 9, 2018
• Last Update Posted: Mar 8, 2021
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin

Study Results

Participant Flow

Arm/Group Title	LY3209590 Algorithm 1	LY3209590 Algorithm 2	Insulin Degludec
Arm/Group Description	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.	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.	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%.
Period Title: Overall Study
STARTED	135	132	132
COMPLETED	118	115	118
NOT COMPLETED	17	17	14

Baseline Characteristics

Arm/Group Title	LY3209590 Algorithm 1	LY3209590 Algorithm 2	Insulin Degludec	Total
Arm/Group Description	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	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.	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 of all reporting groups
Overall Participants	135	132	132	399
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.2 (9.9)	59.6 (11.3)	60.8 (10.0)	60.2 (10.4)
Sex: Female, Male (Count of Participants)
Female	67 49.6%	70 53%	65 49.2%	202 50.6%
Male	68 50.4%	62 47%	67 50.8%	197 49.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	67 49.6%	78 59.1%	73 55.3%	218 54.6%
Not Hispanic or Latino	68 50.4%	54 40.9%	59 44.7%	181 45.4%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	16 11.9%	18 13.6%	19 14.4%	53 13.3%
Asian	4 3%	5 3.8%	6 4.5%	15 3.8%
Native Hawaiian or Other Pacific Islander	1 0.7%	1 0.8%	1 0.8%	3 0.8%
Black or African American	16 11.9%	10 7.6%	10 7.6%	36 9%
White	97 71.9%	97 73.5%	94 71.2%	288 72.2%
More than one race	1 0.7%	0 0%	2 1.5%	3 0.8%
Unknown or Not Reported	0 0%	1 0.8%	0 0%	1 0.3%
Region of Enrollment (Count of Participants)
Puerto Rico	18 13.3%	16 12.1%	15 11.4%	49 12.3%
United States	96 71.1%	97 73.5%	96 72.7%	289 72.4%
Mexico	21 15.6%	19 14.4%	21 15.9%	61 15.3%
Haemoglobin A1c (HbA1c) (HbA1C percentage (%)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [HbA1C percentage (%)]	8.20 (0.87)	8.03 (0.89)	8.13 (0.88)	8.12 (0.88)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in HbA1c
Description	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.
Time Frame	Baseline, Week 32

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	LY3209590 Algorithm 1	LY3209590 Algorithm 2	Insulin Degludec
Arm/Group Description	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.	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.	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%.
Measure Participants	130	125	124
Least Squares Mean (Standard Error) [HbA1C %]	-0.58 (0.083)	-0.57 (0.085)	-0.66 (0.084)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY3209590 Algorithm 1
	Comments
	Type of Statistical Test	Equivalence
	Comments	Equivalence margin is zero.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value reported is within group comparison between Week 32 and baseline.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LY3209590 Algorithm 2
	Comments
	Type of Statistical Test	Equivalence
	Comments	Equivalence margin is zero.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value reported is within group comparison between Week 32 and baseline.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Insulin Degludec
	Comments
	Type of Statistical Test	Equivalence
	Comments	Equivalence margin is zero.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value reported is within group comparison between Week 32 and baseline.
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	Change From Baseline in HbA1c Compared to Insulin Degludec
Description	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.
Time Frame	Baseline, Week 32

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	LY3209590 Algorithm 1	LY3209590 Algorithm 2	Insulin Degludec
Arm/Group Description	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.	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.	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%.
Measure Participants	130	125	124
Least Squares Mean (Standard Error) [HbA1C %]	-0.58 (0.083)	-0.57 (0.085)	-0.66 (0.084)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY3209590 Algorithm 1, Insulin Degludec
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin is 0.4%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 90%; -0.11 to 0.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LY3209590 Algorithm 2, Insulin Degludec
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin is 0.4%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 90%; -0.10 to 0.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Fasting Glucose
Description	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.
Time Frame	Baseline, Week 32

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	LY3209590 Algorithm 1	LY3209590 Algorithm 2	Insulin Degludec
Arm/Group Description	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.	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.	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%.
Measure Participants	130	125	124
Least Squares Mean (Standard Error) [Milligram per deicliter (mg/dL)]	-13.1 (4.01)	-18.6 (4.14)	-31.5 (4.03)

4. Secondary Outcome

Title	Change From Baseline in Insulin Dose (LY3209590)
Description	The baseline for both LY3209590 arms was the first regular weekly dose at Week 1.
Time Frame	Week 1, Week 32

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	LY3209590 Algorithm 1	LY3209590 Algorithm 2
Arm/Group Description	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.	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.
Measure Participants	118	115
Mean (Standard Deviation) [Milligrams (mg)]	0.12 (4.86)	0.60 (3.75)

5. Secondary Outcome

Title	Change From Baseline in Insulin Dose (Insulin Degludec)
Description	Change from Baseline in Insulin Dose for Insulin Degludec arm was reported.
Time Frame	Baseline, Week 32

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec
Arm/Group Description	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%.
Measure Participants	111
Mean (Standard Deviation) [International Units (IU)]	16.40 (26.06)

6. Secondary Outcome

Title	Rate of Total Documented Symptomatic Hypoglycemia
Description	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.
Time Frame	Baseline through week 32

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	LY3209590 Algorithm 1	LY3209590 Algorithm 2	Insulin Degludec
Arm/Group Description	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.	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.	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%.
Measure Participants	135	131	132
Mean (Standard Error) [Events per participant per year]	0.73 (0.119)	1.22 (0.378)	1.56 (0.375)

7. Secondary Outcome

Title	Change From Baseline in Body Weight
Description	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.
Time Frame	Baseline, Week 32

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	LY3209590 Algorithm 1	LY3209590 Algorithm 2	Insulin Degludec
Arm/Group Description	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.	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.	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%.
Measure Participants	135	130	129
Least Squares Mean (Standard Error) [Kilogram (kg)]	1.0 (0.33)	1.0 (0.33)	2.0 (0.33)

8. Secondary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3209590
Description	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.
Time Frame	Week 32

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	LY3209590 Algorithm 1	LY3209590 Algorithm 2
Arm/Group Description	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.	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.
Measure Participants	119	112
Geometric Mean (Geometric Coefficient of Variation) [Nanomole * hour per Liter (nmol * hr/L)]	5360 (67)	5430 (60)

Adverse Events

Time Frame	Up to 37 weeks
Adverse Event Reporting Description	All randomized participants.
Arm/Group Title	LY3209590 Algorithm 1		LY3209590 Algorithm 2		Insulin Degludec
Arm/Group Description	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.		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.		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%.
All Cause Mortality
	LY3209590 Algorithm 1		LY3209590 Algorithm 2		Insulin Degludec
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/135 (0.7%)		0/132 (0%)		1/132 (0.8%)
Serious Adverse Events
	LY3209590 Algorithm 1		LY3209590 Algorithm 2		Insulin Degludec
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/135 (5.2%)		8/132 (6.1%)		10/132 (7.6%)
Cardiac disorders
Acute myocardial infarction	0/135 (0%)	0	0/132 (0%)	0	1/132 (0.8%)	1
Gastrointestinal disorders
Chronic gastritis	0/135 (0%)	0	1/132 (0.8%)	1	0/132 (0%)	0
Nausea	0/135 (0%)	0	1/132 (0.8%)	1	0/132 (0%)	0
Pancreatitis acute	0/135 (0%)	0	1/132 (0.8%)	1	0/132 (0%)	0
Vomiting	0/135 (0%)	0	1/132 (0.8%)	1	0/132 (0%)	0
General disorders
Chest pain	1/135 (0.7%)	1	1/132 (0.8%)	2	0/132 (0%)	0
Non-cardiac chest pain	0/135 (0%)	0	0/132 (0%)	0	1/132 (0.8%)	1
Sudden cardiac death	0/135 (0%)	0	0/132 (0%)	0	1/132 (0.8%)	1
Hepatobiliary disorders
Cholelithiasis	0/135 (0%)	0	1/132 (0.8%)	1	0/132 (0%)	0
Infections and infestations
Abscess limb	1/135 (0.7%)	1	0/132 (0%)	0	0/132 (0%)	0
Cellulitis	1/135 (0.7%)	1	0/132 (0%)	0	0/132 (0%)	0
Meningitis viral	0/135 (0%)	0	0/132 (0%)	0	1/132 (0.8%)	1
Osteomyelitis	1/135 (0.7%)	1	1/132 (0.8%)	1	0/132 (0%)	0
Pneumonia	0/135 (0%)	0	1/132 (0.8%)	1	0/132 (0%)	0
Psoas abscess	0/135 (0%)	0	0/132 (0%)	0	1/132 (0.8%)	1
Sepsis	0/135 (0%)	0	1/132 (0.8%)	1	0/132 (0%)	0
Injury, poisoning and procedural complications
Femur fracture	0/135 (0%)	0	0/132 (0%)	0	1/132 (0.8%)	1
Metabolism and nutrition disorders
Dehydration	0/135 (0%)	0	1/132 (0.8%)	1	0/132 (0%)	0
Hypoglycaemia	0/135 (0%)	0	2/132 (1.5%)	2	0/132 (0%)	0
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/135 (0%)	0	0/132 (0%)	0	1/132 (0.8%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/135 (0%)	0	0/132 (0%)	0	1/132 (0.8%)	1
Metastatic neoplasm	1/135 (0.7%)	1	0/132 (0%)	0	0/132 (0%)	0
Transitional cell carcinoma	1/135 (0.7%)	1	0/132 (0%)	0	0/132 (0%)	0
Nervous system disorders
Ischaemic stroke	0/135 (0%)	0	0/132 (0%)	0	1/132 (0.8%)	1
Syncope	0/135 (0%)	0	0/132 (0%)	0	1/132 (0.8%)	1
Psychiatric disorders
Mental status changes	0/135 (0%)	0	0/132 (0%)	0	1/132 (0.8%)	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/135 (0%)	0	1/132 (0.8%)	1	0/132 (0%)	0
Skin and subcutaneous tissue disorders
Diabetic foot	1/135 (0.7%)	1	0/132 (0%)	0	0/132 (0%)	0
Vascular disorders
Arteriosclerosis	1/135 (0.7%)	1	0/132 (0%)	0	0/132 (0%)	0
Hypertensive emergency	0/135 (0%)	0	1/132 (0.8%)	1	0/132 (0%)	0
Other (Not Including Serious) Adverse Events
	LY3209590 Algorithm 1		LY3209590 Algorithm 2		Insulin Degludec
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/135 (12.6%)		29/132 (22%)		13/132 (9.8%)
Gastrointestinal disorders
Diarrhoea	9/135 (6.7%)	10	8/132 (6.1%)	9	2/132 (1.5%)	2
Infections and infestations
Upper respiratory tract infection	8/135 (5.9%)	8	14/132 (10.6%)	14	6/132 (4.5%)	6
Nervous system disorders
Dizziness	1/135 (0.7%)	1	7/132 (5.3%)	7	1/132 (0.8%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/135 (0.7%)	1	5/132 (3.8%)	5	7/132 (5.3%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.