A Study of LY900014 in Adult Participants With Type 2 Diabetes Mellitus in India

• Insulin Lispro-aabc (Drug), also known as LY900014, Lyumjev: Administered subcutaneously
• Insulin Glargine (Drug), also known as Basaglar: Administered subcutaneously

Primary outcomes

• Percentage of Participants With at Least 1 Documented Hypoglycemic Event With Blood Glucose <54 Milligrams Per Deciliter (mg/dL) [Baseline through Week 26]: The percentage of participants with at least 1 documented hypoglycemic event was calculated as the number of participants with >=1 documented hypoglycemic event divided by the total number of participants, multiplied by 100.
• Rate of Documented Hypoglycemia With Blood Glucose <54 mg/dL [Baseline through Week 26]: Rate of documented hypoglycemia (events/participant/year) was calculated as the sum of documented hypoglycemic episodes divided by the cumulative days on treatment from all participants, multiplied by 365.

Secondary outcomes

• Percentage of Participants With Severe Hypoglycemia [Baseline through Week 26]: * Severe hypoglycemia is considered any hypoglycemic event where the participant requires assistance for recovery with or without hospitalisation and is reported as a serious adverse event. * The percentage of participants with at least 1 severe hypoglycemic event was calculated as the number of participants with >=1 severe hypoglycemic event divided by the total number of participants, multiplied by 100.
• Percentage of Participants With at Least 1 Nocturnal Hypoglycemic Event With Blood Glucose <54 mg/dL [Baseline through Week 26]: * Nocturnal hypoglycemia is considered any hypoglycemic event (documented hypoglycemia or probable symptomatic hypoglycemia, including severe hypoglycemia) that occurs between bedtime and waking (11:59 PM to 5:59 AM). * The percentage of participants with at least 1 nocturnal hypoglycemic event was calculated as the number of participants with >=1 nocturnal hypoglycemic event divided by the total number of participants, multiplied by 100.
• Rate of Nocturnal Hypoglycemia With Blood Glucose <54 mg/dL [Baseline through Week 26]: * Nocturnal hypoglycemia is considered any hypoglycemic event (documented hypoglycemia or probable symptomatic hypoglycemia, including severe hypoglycemia) that occurs between bedtime and waking (11:59 PM to 5:59 AM). * Rate of nocturnal hypoglycemia (events/participant/year) was calculated as the sum of nocturnal hypoglycemic episodes divided by the cumulative days on treatment from all participants, multiplied by 365.
• Percentage of Participants With at Least 1 Nocturnal Hypoglycemic Event With Blood Glucose <70 mg/dL [Baseline through Week 26]: * Nocturnal hypoglycemia is considered any hypoglycemic event (documented hypoglycemia or probable symptomatic hypoglycemia, including severe hypoglycemia) that occurs between bedtime and waking (11:59 PM to 5:59 AM). * The percentage of participants with at least 1 nocturnal hypoglycemic event was calculated as the number of participants with >=1 nocturnal hypoglycemic event divided by the total number of participants, multiplied by 100.
• Rate of Nocturnal Hypoglycemia With Blood Glucose <70 mg/dL [Baseline through Week 26]: * Nocturnal hypoglycemia is considered any hypoglycemic event (documented hypoglycemia or probable symptomatic hypoglycemia, including severe hypoglycemia) that occurs between bedtime and waking (11:59 PM to 5:59 AM). * Rate of nocturnal hypoglycemia (events/participant/year) was calculated as the sum of nocturnal hypoglycemic episodes divided by the cumulative days on treatment from all participants, multiplied by 365.
• Percentage of Participants With at Least 1 Documented Hypoglycemic Event With Blood Glucose <70 mg/dL [Baseline through Week 26]: The percentage of participants with at least 1 documented hypoglycemic event was calculated as the number of participants with >=1 documented hypoglycemic event divided by the total number of participants, multiplied by 100.
• Rate of Documented Hypoglycemia With Blood Glucose <70 mg/dL [Baseline through Week 26]: Rate of documented hypoglycemia (events/participant/year) was calculated as the sum of documented hypoglycemic episodes divided by the cumulative days on treatment from all participants, multiplied by 365.
• Change From Baseline in Body Weight [Baseline, Week 26]
• Change From Baseline in Hemoglobin A1c (HbA1c) [Baseline, Week 26]: HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time.
• Percentage of Participants Achieving HbA1c < 7% [Week 26]: HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time.
• Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) Score [Baseline, Week 26]: The ITSQ is a 22-item questionnaire that assesses treatment satisfaction for participants taking insulin under 5 domains: Inconvenience of Regimen \[5 items\], Lifestyle Flexibility \[3 items\], Glycemic Control \[3 items\], Hypoglycemic Control \[5 items\], Insulin Delivery Device \[6 items\]. Each Item is measured on a 7-point scale. The overall score is calculated as the mean of all 22 items and transformed to a scale of 0 to 100 using the formula: 100*\[(7 - raw overall score)/6\], with higher scores indicating better treatment satisfaction.
• Change From Baseline in 1- and 2-hour Postprandial Glucose (PPG) Values Estimated From Self-monitored Blood Glucose (SMBG) Values [Baseline, Day 3 of Week 20]
• Change From Baseline in Bolus Insulin Dose, Basal Insulin Dose [Baseline, Week 20]: * Bolus insulin dose, calculated as the summed daily bolus insulin dose across days 1, 2 and 3 divided by the number of non-missing data days. * Basal insulin dose, calculated as the summed daily basal insulin dose across days 1, 2 and 3 divided by the number of non-missing data days.
• Change From Baseline in Basal to Bolus Insulin Dose Ratio [Baseline, Week 20]: Basal to Bolus insulin dose ratio, calculated as the basal insulin dose divided by the basal insulin dose. * Bolus insulin dose, calculated as the summed daily bolus insulin dose across days 1, 2 and 3 divided by the number of non-missing data days. * Basal insulin dose, calculated as the summed daily basal insulin dose across days 1, 2 and 3 divided by the number of non-missing data days
• Change From Baseline in 9-Point Self-Monitored Blood Glucose (SMBG) Values [Baseline, Week 20]: SMBG measurements were taken at 9 time points: fasting, 1 hour post-breakfast, 2 hours post-breakfast, pre-lunch, 1 hour post-lunch, 2 hours post-lunch, pre-dinner, 1 hour post-dinner, and 2 hours post-dinner. The SMBG value was calculated as the average of the corresponding SMBG measurements collected on Days 1, 2, and 3 across cumulative non-missing data days.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Have Type 2 Diabetes Mellitus (T2DM) for ≥1 year prior to screening
* Treated for ≥90 days prior to screening with multiple daily injection (MDI) therapy

  * on basal insulin or insulin glargine 100 U/mL \[Basaglar or Lantus\] or insulin glargin 300 U/mL, insulin determir, insulin degludec U-100, or neutral protamine Hagedorn (NPH) insulin) in combination with at least 1 prandial injection of bolus insulin (insulin lispro 100 U/mL or 200 U/mL, insulin aspart, insulin glulisine, regular insulin, fast-acting insulin aspart), or
  * premixed analog or human insulin regimens with any basal and bolus insulin
* May have been treated with up to 3 oral antihyperglycemic medications (OAMs) including metformin, sodium-glucose cotransporter (SGLT)-2 inhibitor in accordance with local regulations. The dose of all OAMs must have been stable for ≥90 days prior to screening
* Have an HbA1c value ≥7.5% and ≤10% according to the central laboratory at screening
* Body mass index ≤45.0 kg/m²
* Have access to a telephone, or alternative means for close monitoring/communications
* Have refrigeration at home or have ready access to refrigeration for storage of insulin therapy
* Have a regular wake-sleep schedule (awake-work during the day and sleep during the night)

Exclusion Criteria:

* Having any other condition (including known drug or alcohol abuse, psychiatric disorder including eating disorder) that precludes the subject from following and completing the protocol
* Have been diagnosed, at any time, with type 1 diabetes mellitus (T1DM) or latent autoimmune diabetes in adults
* Have hypoglycemia unawareness as judged by the investigator
* Have had any episode of severe hypoglycemia (defined as requiring assistance due to neurologically disabling hypoglycemia) within the 6 months prior to screening
* Have had 1 or more episodes of diabetic ketoacidosis or hyperglycemic hyperosmolar state within the 6 months prior to screening
* Have a known diagnosis of secondary diabetes (for example, diabetes caused by hemochromatosis, acromegaly, chronic pancreatitis, or pancreatectomy)
* Excessive insulin resistance defined as having received a total daily dose of insulin >2.0 U/kg at the time of screening
* Have a history of or are being evaluated for bariatric surgery including Roux-en-Y gastric bypass surgery, gastric banding, and/or gastric sleeve
* Have cardiovascular disease, within the past 6 months prior to screening, defined as stroke, decompensated heart failure (New York Heart Association Class III or IV), myocardial infarction, unstable angina pectoris, or coronary arterial bypass graft
* History of renal transplantation
* Currently receiving renal dialysis
* Serum creatinine >2.0 mg/dL (177 µmol/L) at screening
* Have obvious clinical signs or symptoms of liver disease (for example, acute or chronic hepatitis or cirrhosis), or elevated liver enzyme measurements
* Have active or untreated malignancy, have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer) for less than 5 years, or are at an increased risk for developing cancer or a recurrence of cancer in the opinion of the investigator
* Have had a blood transfusion or severe blood loss within 90 days prior to screening or have known hemoglobinopathy, anemia, or any other traits known to interfere with measurement of HbA1
* Have presence of clinically significant gastrointestinal disease (for example, clinically active gastroparesis associated with wide glucose fluctuations) in the investigator's opinion
* Have used thiazolidinediones, glucagon-like peptide 1 receptor agonist, or pramlintide within 90 days prior to screening

Participant flow

Outcome results

• Percentage of Participants With at Least 1 Documented Hypoglycemic Event With Blood Glucose <54 Milligrams Per Deciliter (mg/dL) (Primary), Number, percentage of participants: Insulin Lispro-aabc 4
• Rate of Documented Hypoglycemia With Blood Glucose <54 mg/dL (Primary), Number, events/participant/year: Insulin Lispro-aabc 0.08
• Percentage of Participants With Severe Hypoglycemia (Secondary), Number, Percentage of participants: Insulin Lispro-aabc 0
• Percentage of Participants With at Least 1 Nocturnal Hypoglycemic Event With Blood Glucose <54 mg/dL (Secondary), Number, percentage of participants: Insulin Lispro-aabc 0.7
• Rate of Nocturnal Hypoglycemia With Blood Glucose <54 mg/dL (Secondary), Number, events/participant/year: Insulin Lispro-aabc 0.01
• Percentage of Participants With at Least 1 Nocturnal Hypoglycemic Event With Blood Glucose <70 mg/dL (Secondary), Number, percentage of participants: Insulin Lispro-aabc 4
• Rate of Nocturnal Hypoglycemia With Blood Glucose <70 mg/dL (Secondary), Number, events/participant/year: Insulin Lispro-aabc 0.08
• Percentage of Participants With at Least 1 Documented Hypoglycemic Event With Blood Glucose <70 mg/dL (Secondary), Number, percentage of participants: Insulin Lispro-aabc 22
• Rate of Documented Hypoglycemia With Blood Glucose <70 mg/dL (Secondary), Number, events/participant/year: Insulin Lispro-aabc 0.77
• Change From Baseline in Body Weight (Secondary), Least squares mean, kilogram (kg): Insulin Lispro-aabc 0.3 +/- 0.18
• Change From Baseline in Hemoglobin A1c (HbA1c) (Secondary), Least squares mean, percentage of HbA1c: Insulin Lispro-aabc -0.8 +/- 0.11
• Percentage of Participants Achieving HbA1c < 7% (Secondary), Number, percentage of participants: Insulin Lispro-aabc 21.6
• Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) Score (Secondary), Least squares mean, score on a scale: Insulin Lispro-aabc 5.7 +/- 0.86
• Change From Baseline in 1- and 2-hour Postprandial Glucose (PPG) Values Estimated From Self-monitored Blood Glucose (SMBG) Values (Secondary), Least squares mean, mg/dL: Insulin Lispro-aabc -19.2 +/- 3.29
• Change From Baseline in Bolus Insulin Dose, Basal Insulin Dose (Secondary), Least squares mean, Units/day: Insulin Lispro-aabc 3.5 +/- 0.72
• Change From Baseline in Basal to Bolus Insulin Dose Ratio (Secondary), Least squares mean, ratio: Insulin Lispro-aabc 0.0 +/- 0.02
• Change From Baseline in 9-Point Self-Monitored Blood Glucose (SMBG) Values (Secondary), Mean, mg/dL: Insulin Lispro-aabc -18.0 +/- 40.57

Adverse events

Time frame: Baseline to end of safety follow-up (up to 42 weeks)

Serious adverse events by term

Other adverse events by term

• Study Protocol (PDF, 2024-01-03)
• Statistical Analysis Plan (PDF, 2020-11-12)

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