A Study of LY3209590 in Participants With Type 2 Diabetes Mellitus

Study Overview
=================
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.

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

Conditions
-----------------
Type 2 Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: LY3209590
* Drug: Insulin Degludec


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3209590 Algorithm 1<br>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<br>* Administered SC<br>|
| Experimental: LY3209590 Algorithm 2<br>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<br>* Administered SC<br>|
| Active Comparator: Insulin Degludec<br>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<br>* Administered SC<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c | 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. | Baseline, Week 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c Compared to Insulin Degludec | 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. | Baseline, Week 32 | 
| Change From Baseline in Fasting Glucose | 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. | Baseline, Week 32 | 
| Change From Baseline in Insulin Dose (LY3209590) | The baseline for both LY3209590 arms was the first regular weekly dose at Week 1. | Week 1, Week 32 | 
| Change From Baseline in Insulin Dose (Insulin Degludec) | Change from Baseline in Insulin Dose for Insulin Degludec arm was reported. | Baseline, Week 32 | 
| Rate of Total Documented Symptomatic Hypoglycemia | 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. | Baseline through week 32 | 
| Change From Baseline in Body Weight | 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. | Baseline, Week 32 | 
| Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3209590 | 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. | Week 32 |