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

Phase 3
Completed
Conditions
Type 2 Diabetes Mellitus
Interventions
Registration Number
NCT03952143
Lead Sponsor
Eli Lilly and Company
Brief Summary

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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
628
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
LY900014LY900014Participants 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.
LY900014Insulin GlargineParticipants 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.
LY900014Insulin DegludecParticipants 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.
Insulin LisproInsulin DegludecParticipants 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.
Insulin LisproInsulin GlargineParticipants 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.
Insulin LisproInsulin LisproParticipants 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.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Hemoglobin A1c (HbA1c)Baseline, Week 26

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).

Secondary Outcome Measures
NameTimeMethod
2-hour PPG Excursion During MMTTWeek 26

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).

Percentage of Participants With HbA1c <7% and ≤6.5%Week 26

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.

1-hour Postprandial Glucose (PPG) Excursion During Mixed-Meal Tolerance Test (MMTT)Week 26

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).

Rate of Documented Symptomatic Postmeal HypoglycemiaBaseline through Week 26

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

Change From Baseline in 1,5-Anhydroglucitol (1,5-AG)Baseline, Week 26

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)

Change From Baseline in Insulin DoseBaseline, Week 26

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)

Rate of Severe HypoglycemiaBaseline through Week 26

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.

Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) ValuesBaseline, Week 26

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).

Trial Locations

Locations (41)

Dalian Municipal Central Hospital Affiliated of Dalian Medical University

🇨🇳

Dalian, Cn-21, China

Shengjing Hospital of China Medical University

🇨🇳

Shenyang, Cn-21, China

Shanghai Putuo District Center Hospital

🇨🇳

Shanghai, Cn-31, China

The Central Hospital of Wuhan

🇨🇳

Wuhan, Cn-42, China

The First People's Hospital of Yueyang

🇨🇳

Yueyang, Cn-43, China

Chongqing General Hospital

🇨🇳

Chongqing, Cn-50, China

Xingtai People's Hospital

🇨🇳

Xingtai, Hebei, China

The Fourth Affiliated Hospital of Harbin Medical University

🇨🇳

Harbin, Heilongjiang, China

The First Hospital of Qiqihar

🇨🇳

Qiqihar, Heilongjiang, China

Wuhan Pu'ai Hospital

🇨🇳

Wuhan, Hubei, China

The First Hospital of Nanjing

🇨🇳

Nanjing, Jiangsu, China

Beijing Peking Union Medical College Hospital

🇨🇳

Beijing, China

Jinan Central Hospital

🇨🇳

Jinan, Shandong, China

Unidad Médica para la Salud Integral

🇲🇽

San Nicolás de los Garza, Mx-nle, Mexico

Centro de Inv. Medica de Occidente, SC

🇲🇽

Zapopan, Jalisco, Mexico

Hospital Universitario Dr. Jose Eleuterio Gonzalez

🇲🇽

Monterrey, N.l., Mexico

Tianjin Medical University General Hospital

🇨🇳

Tianjin, Cn-12, China

Cangzhou People's Hospital

🇨🇳

Cangzhou, Cn-13, China

Beijing Pinggu District Hospital

🇨🇳

Beijing, Cn-11, China

Centro Médico Viamonte

🇦🇷

Buenos Aires, Ar-c, Argentina

The First Hospital of Qinhuangdao

🇨🇳

Qinhuangdao Shi, Cn-13, China

Inner Mongolia People's Hospital

🇨🇳

Hohhot, Cn-15, China

Nanjing Medical University - Nanjing Jiangning Hospital

🇨🇳

Nanjing, Cn-32, China

Affiliated Hospital of Jiangsu University

🇨🇳

Zhenjiang, Cn-32, China

Chenzhou NO.1 People's Hospital

🇨🇳

Chenzhou, Hunan, China

Cent Priva Especiali Médicas Ambulatorias Inve Clin CEMAIC

🇦🇷

Cordoba, Argentina

Centro de Investigaciones Metabólicas (CINME)

🇦🇷

Caba, Buenos Aires, Argentina

Shanghai 6th people's hospital

🇨🇳

Shanghai, Cn-31, China

The Affiliated Jiangyin Hospital of Southeast University Medical College

🇨🇳

Jiangyin, Cn-32, China

Zhongda Hospital Southeast University

🇨🇳

Nanjing, Cn-32, China

The Third Hospital of Nanchang

🇨🇳

Nanchang, Cn-36, China

Fujian Medical University Union Hospital

🇨🇳

Fuzhou, Fujian, China

The First Affiliated Hospital of Henan University of Science &Technology

🇨🇳

Luoyang, Henan, China

Yichang Central People's Hospital

🇨🇳

Yichang, Hubei, China

Changzhou No.2 People's Hospital

🇨🇳

Changzhou, Jiangsu, China

The First Affiliated Hospital of Xi'an Medical University

🇨🇳

XI 'an, Shanxi, China

China-Japan Union Hospital, CJUH.

🇨🇳

Changchun, Jilin, China

Siping Central People's Hospital

🇨🇳

Siping, Jilin, China

Qinghai University Affiliated Hospital

🇨🇳

Xining, Qinghai, China

Unidad de patologia Clinica

🇲🇽

Guadalajara, Jalisco, Mexico

Pingxiang People's Hospital

🇨🇳

Pingxiang, China

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