A Study of LY900014 Compared to Insulin Lispro (Humalog) in Adults With Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to see if LY900014 compared to insulin lispro (Humalog), both in combination with insulin glargine or insulin degludec, is safe and effective in participants with type 2 diabetes (T2D).

Official Title
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A Prospective, Randomized, Double-Blind Comparison of LY900014 to Insulin Lispro, Both in Combination With Insulin Glargine or Insulin Degludec in Adults With Type 2 Diabetes

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: LY900014
* Drug: Insulin Lispro
* Drug: Insulin Glargine
* Drug: Insulin Degludec


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have T2D based on the disease diagnostic criteria World Health Organization (WHO) classification. Participants must have been treated for at least 90 days prior to screening with either basal insulin + at least 1 prandial injection of bolus insulin or premixed analog/human insulin regimens at least twice daily. Participants must be treated no more than 3 oral anti-hyperglycemic medications (OAMs). Participants must have a HbA1c ≥7.0% and ≤11.0%. Participants must have body mass index (BMI) of ≤35.0 kilograms per meter squared (kg/m2). Exclusion Criteria: Participants must not have been diagnosed, at any time, with type 1 diabetes (T1D) or latent autoimmune diabetes in adults. Participants must not have had any episode of severe hypoglycemia within the 6 months prior to screening. Participants must not have had 1 or more episodes of diabetic ketoacidosis or hyperglycemic hyperosmolar state within the 6 months prior to screening. Participants must not have used thiazolidinediones, glucagon-like peptide 1 (GLP-1) receptor agonist, or pramlintide within 90 days prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY900014<br>Participants received 100 units per milliliter (U/mL) LY900014 subcutaneously (SC) 0-2 minutes before each meal with either basal insulin glargine or insulin degludec given SC once daily. | Drug: LY900014<br>* Administered SC<br>* Other names: Ultra-Rapid Lispro;Drug: Insulin Glargine<br>* Administered SC<br>Drug: Insulin Degludec<br>* Administered SC<br>|
| Active Comparator: Insulin Lispro<br>Participants received 100 U/mL insulin lispro (Humalog) given SC 0-2 minutes before each meal with either basal insulin glargine or insulin degludec given SC once daily. | Drug: Insulin Lispro<br>* Administered SC<br>* Other names: Humalog;Drug: Insulin Glargine<br>* Administered SC<br>Drug: Insulin Degludec<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin A1c (HbA1c) | 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 + Pooled Country + Number of Bolus at Study Entry Stratum + Type of Basal at Lead-in Stratum + Treatment + Time + Treatment*Time (Type III sum of squares). | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-hour Postprandial Glucose (PPG) Excursion During Mixed-Meal Tolerance Test (MMTT) | A standardized MMTT was used to characterize postprandial glucose control following administration of the study insulin. Serum glucose measured at 1-hour timepoint after the start of meal minus fasting serum glucose. Least Squares (LS) mean was determined by analysis of covariance (ANCOVA) model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Number of Bolus at Study Entry Stratum + Type of Basal at Lead-in Stratum + Treatment (Type III sum of squares). | Week 26 | 
| 2-hour PPG Excursion During MMTT | A standardized MMTT was used to characterize postprandial glucose control following administration of the study insulin. Serum glucose measured at 2-hour timepoint after the start of meal minus fasting serum glucose. Least Squares (LS) mean was determined by analysis of covariance (ANCOVA) model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Number of Bolus at Study Entry Stratum + Type of Basal at Lead-in Stratum + Treatment (Type III sum of squares). | Week 26 | 
| Rate of Severe Hypoglycemia | Severe hypoglycemia is defined as an event requiring assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. Rate of severe hypoglycemia events per 100 years during a defined period was calculated by total number of severe hypoglycemia episodes within the period divided by the cumulative days on treatment from all participants within that treatment group *36525. | Baseline through Week 26 | 
| Rate of Documented Symptomatic Postmeal Hypoglycemia | Documented symptomatic postmeal hypoglycemia is an event during which typical symptoms of hypoglycemia are accompanied by blood glucose (BG) of ≤70 mg/dL [3.9 millimole per liter (mmol/L)]. The rate of documented symptomatic postmeal hypoglycemia was estimated by negative binomial model: number of episodes = treatment with log (treatment exposure in days/365.25) as an offset variable | Baseline through Week 26 | 
| Change From Baseline in 1,5-Anhydroglucitol (1,5-AG) | 1,5-anhydroglucitol (1,5-AG) is a marker of short-term glycemic control especially postprandial hyperglycemia. 1,5-AG accurately predicts rapid changes in glycemia and is tightly associated with glucose fluctuations and postprandial glucose. LS Mean was calculated using mixed model repeated measures (MMRM) with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Number of Bolus at Study Entry Stratum + Type of Basal at Lead-in Stratum + Treatment + Time + Treatment*Time (Type III sum of squares) | Baseline, Week 26 | 
| Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values | SMBG 10-point profiles were measured at fasting, 1-hour post morning meal, 2-hours post morning meal, pre midday meal, 1-hour post midday meal, 2-hours post midday meal, pre evening meal, 1-hour post evening meal, 2-hours post evening meal, and bedtime. LS Mean was analyzed using mixed model repeated measures (MMRM) model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Number of Bolus at Study Entry Stratum + Type of Basal at Lead-in Stratum + Treatment + Time + Treatment*Time (Type III sum of squares). | Baseline, Week 26 | 
| Change From Baseline in Insulin Dose | LS mean was determined by MMRM model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Number of Bolus at Study Entry Stratum + Type of Basal at Lead-in Stratum + Treatment + Time + Treatment*Time (Type III sum of squares) | Baseline, Week 26 | 
| Percentage of Participants With HbA1c <7% and ≤6.5% | Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Only subjects with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis. | Week 26 |