Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Insulin Peglispro, Basal Insulin Peglispro
LY2605541 · 17 trials · 6 indications
The percentage was calculated by dividing the number of participants with clinically significant hypoglycemia events defined as blood glucose \<54 milligrams per deciliter (mg/dL) (3.0 millimole per liter \[mmol/L\]) or symptoms of severe hypoglycemia by the total number of participants analyzed, multiplied by 100.
Hemoglobin A1c (HbA1c) is a test that measures a participant's average blood glucose level over the past 2 to 3 months. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis adjusting for treatment, stratification factors (region, sulfonylureas/meglitinide use, baseline Low-Density Lipoprotein \[LDL-C\], visit, treatment-by-visit interaction, and baseline HbA1c as fixed effects and participants as the random effect. P-value is from MMRM with terms for treatment, visit, treatment-by-visit interaction, stratification, and baseline HbA1C.
Glycosylated hemoglobin A1 (HbA1c) is a test that measures a participant's average blood glucose level over a 2 to 3 month timeframe. Least Squares (LS) means were calculated by mixed model repeated measures (MMRM) using treatment, stratification factors (country, sulfonylureas/meglitinide use \[Yes/No\]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects.
HbA1c is a test that measures a person's average blood glucose level over the past 2 to 3 months. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis including the following fixed effects: treatment, period, sequence, baseline HbA1c (last nonmissing value at or before randomization), week (defined from the start of each Randomization Period), and treatment-by-week interaction.
HbA1c is a test that measures a participant's average blood glucose level over a 2 to 3 month timeframe. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for stratification factors (country, baseline low-density lipoprotein cholesterol \[LDL-C, \<100 milligrams per deciliter (mg/dL) and ≥100 mg/dL\], and sulfonylurea (SU) or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline HbA1c.
HbA1c is a test that measures a participant's average blood glucose level over a 2 to 3 month timeframe. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for stratification factors (country, low-density lipoprotein cholesterol \[LDL-C, \<100 milligrams per deciliter (mg/dL) and ≥100 mg/dL\], and number of insulin injections at baseline \[1, 2, or ≥3\]), visit, treatment, visit-by-treatment interaction, and baseline HbA1c.
8-point SMBG profiles are measured at morning FBG, midday and evening pre-meal blood glucose (BG), 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. Least squares (LS) mean of the FBG is from mixed-model repeated measures (MMRM) approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-interim analysis \[IA\], post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline hemoglobin A1c \[HbA1c\] group); visit; visit and treatment interaction; random effect for participant.
It is the Avg. of the 8-point SMBG profiles, BG of morning fasting, midday \& evening pre-meal, 2-hour postprandial after each of the 3 main meals, bedtime, 0300 hours. Least squares (LS) mean of daily Avg. BG is from mixed-model repeated measures (MMRM), which includes fixed effects of treatment (LY2605541, Glargine); Treatment Sequence; treatment period; dose conversion (pre-interim analysis \[IA\], post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline Hemoglobin \[HbA1c\] group); visit; visit and treatment interaction; a random effect for participant.
During the euglycemic 2-step hyperinsulinemic clamp, both low and high insulin was infused sequentially during the same procedure. The 2-step clamp procedure allowed insulin sensitivity to be measured in participants and uses a lower dose of insulin of which the effect is largely on the liver and a high dose of insulin at which the effect has reached 100% on liver and effects are largely on glucose uptake in peripheral tissues. Measurements for average glucose infusion rate are collected for both steps (low and high) of the clamp procedure.
To quantitate the pharmacodynamic (PD) effect of a range of prandial insulin lispro doses after treatment with insulin peglispro (LY2605541) compared to insulin glargine during a meal tolerance test (MTT), with sequenced doses of insulin lispro ranging from 25% to 150% of each participant's normal dose. Data presented as hours times milligrams per deciliter (mg\*h/dL)
Absolute concentration of ISF of insulin peglispro and human insulin.
Lipid or glucose metabolism was assessed by the measurement of respiratory quotient (RQ) during sleep using whole room calorimetry. RQ is a calculation of basal metabolic rate (BMR) when estimated from carbon dioxide production. It is calculated from the ratio of carbon dioxide produced by the body to oxygen consumed by the body using whole room calorimetry (WRC).
VLDL-TG average total concentration calculated at steady state from 240 to 420 minutes during dosing with insulin peglispro and insulin glargine.
VLDL-TG secretion rates are calculated at steady state during dosing with insulin peglispro and insulin glargine.
VLDL-TG oxidation rates are calculated at steady state during dosing with insulin peglispro and insulin glargine.
VLDL-TG clearance rates are calculated at steady state during dosing with insulin peglispro and insulin glargine.
Venous blood samples for pharmacokinetic analysis were collected during the euglycemic glucose clamps during Part A. The intra-participant percentage of coefficient of variation (%CV) is presented. %CV was calculated by dividing the standard deviation by the mean, multiplied by 100.
Venous blood samples for pharmacokinetic analysis were collected during the euglycemic glucose clamps during Part A. The intra-participant percentage of coefficient of variation (%CV) is presented. %CV was calculated by dividing the standard deviation by the mean, multiplied by 100.
Epinephrine levels are presented. Each participant's measurements at 30, 15, and 0 minutes preclamp on the day of the clamp were averaged for the baseline value, and measurements at blood glucose (BG) level attainment and +10, 20, and 30 minutes were averaged for the BG nadir value.
The percent suppression from baseline in endogenous glucose production (EGP) is presented. Percent EGP change from baseline was calculated by (1-\[last 2 hours of EGP/basal EGP\])\*100. The duration of the clamp procedure was 10 hours for the LY2605541 74.1 mU/min dose in Part B. The duration of the clamp procedures performed at the 15.3 mU/min LY2605541 dose and both of the insulin glargine doses was 8 hours.
The fold change from baseline in glucose disappearance rate (GDR) is presented. The fold GDR increase from baseline was calculated by last 2 hours of GDR/basal GDR. The duration of the clamp procedure was 10 hours for the LY2605541 74.1 mU/min dose in Part B. The duration of the clamp procedures performed at the 15.3 mU/min LY2605541 dose and both of the insulin glargine doses was 8 hours.
The maximum rate of glucose disposal (Rdmax) is presented. The duration of the clamp procedure was 10 hours for the LY2605541 74.1 mU/min dose in Part B. The duration of the clamp procedures performed at the 15.3 mU/min LY2605541 dose and both of the insulin glargine doses was 8 hours.
| Arm | Type | Description |
|---|---|---|
| Insulin Peglispro | EXPERIMENTAL | Standard dose of insulin peglispro administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin peglispro administered once, SQ on day 3 of the inpatient stay. |
| Insulin Glargine | EXPERIMENTAL | Standard dose of insulin glargine administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin glargine administered once, SQ on day 3 of the inpatient stay. |
| LY2605541 | EXPERIMENTAL | Administered by subcutaneous (SC) injection once daily in the morning or at bedtime. Initial dose is 10 units (or less for some of the participants in Korea) and is adjusted weekly based on Fasting Blood Glucose (FBG). LY2605541 will be given alone or in combination with up to 3 pre-study oral antihyperglycemic medications \[OAM(s)\] whose use is not excluded in combination with insulin. Treatment may last up to 26 weeks. |
| Human Insulin NPH | ACTIVE_COMPARATOR | Administered by SC injection once daily at bedtime. Initial dose is 10 units (or less for some of the participants in Korea) and is adjusted weekly based on FBG. Human insulin NPH will be used alone or in combination with up to 3 pre-study OAM(s) whose use is not excluded in combination with insulin. Treatment may last up to 26 weeks. Some participants who are unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may be asked to add a second injection prior to the morning meal. |
| LY2605541 Fixed Time Dosing | EXPERIMENTAL | Participant-specific dose of LY2605541 administered subcutaneously (SQ) at approximately the same time every evening for 12 weeks in the Lead-in Period and in Randomization Period 1 or Randomization Period 2. Participant-specific dose of insulin lispro SQ when \>20% of calories were consumed (pre-meal). Insulin dose and adjustments to insulin dose were determined by insulin algorithms based on self-monitored blood glucose (SMBG). Target glucose values were as follows: Preprandial and bedtime BG between 71 and 130 milligrams/deciliter (mg/dL) Insulin adjustment and glucose correction between 71 and 100 mg/dL. |
| LY2605541 Variable Time Dosing | EXPERIMENTAL | Participant-specific dose of LY2605541 administered SQ on a variable time schedule (8- and 40-hour dosing intervals) for 12 weeks in Randomization Period 1 or Randomization Period 2. Dosing schedules were to remain approximately the same throughout the 12 weeks. Participant-specific dose of insulin lispro SQ when \>20% of calories were consumed (pre-meal). Insulin dose and adjustments to insulin dose were determined by insulin algorithms based on SMBG. Target glucose values were as follows: Preprandial and bedtime BG between 71 and 130 mg/dL Insulin adjustment and glucose correction between 71 and 100 mg/dL. |
| Insulin Glargine + Insulin Lispro | ACTIVE_COMPARATOR | Participant-specific dose of Insulin Glargine will be administered subcutaneously (SC) once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro will be administered SC for preprandial (pre-meal) and supplemental doses for 26 weeks. |
| LY2605541 + Insulin Lispro | EXPERIMENTAL | Participant-specific dose of LY2605541 will be administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro will be administered SC for preprandial and supplemental doses for 26 weeks. |
| LY2605541 Dosing Algorithm 1 | EXPERIMENTAL | Participants took both LY2605541 and their pre-study insulin for first several days |
| LY2605541 Dosing Algorithm 2 | EXPERIMENTAL | Participants took only LY2605541 with first dose doubled |
| LY2605541 First, Then Insulin Glargine | EXPERIMENTAL | Participants received LY2605541 for 8 weeks, followed by insulin glargine for 8 weeks. |
| Insulin Glargine First, Then LY2605541 | ACTIVE_COMPARATOR | Participants received insulin glargine for 8 weeks, followed by LY2605541 for 8 weeks. |
| Insulin Peglispro (with Insulin Lispro) | EXPERIMENTAL | Insulin peglispro, a once daily subcutaneous(SC) injection at bedtime for 5 weeks |
| Insulin Glargine (with Insulin Lispro) | ACTIVE_COMPARATOR | Insulin glargine, a once daily subcutaneous(SC) injection at bedtime for 5 weeks |
| Insulin peglispro (LY2605541, with Insulin Lispro) | EXPERIMENTAL | Insulin peglispro (LY2605541) once daily subcutaneous (SC) injection at bedtime. Insulin lispro given SC prandially or as bolus as required |
| Insulin Peglispro (LY2605541) | EXPERIMENTAL | Part A Cohort 1: (low dose) priming dose (PD) of 2.00 units (U), 0.92 U/hour (U/h) constant infusion of insulin peglispro Part A Cohort 1: (high dose) PD of 8.00 U, 4.50 U/h constant IV infusion of insulin peglispro Part A Cohort 2: (intermediate dose 1) PD of 4.00 U, 1.84/h constant IV infusion of insulin peglispro Part A Cohort 2: (intermediate dose 2) PD of 6.0 U, 2.76 U/h constant IV infusion of insulin peglispro Part B Insulin Peglispro: PD of 6.00 U, 2.76 constant IV infusion of insulin peglispro and a constant infusion of 6 pico moles per kilogram per minute (pmol/kg/min). IV infusion of sinistrin (250 mg/mL, SOC to achieve a steady state for up to 16 hours). |
| Human Insulin | ACTIVE_COMPARATOR | Constant IV infusion ( 6 pico moles per kilogram perminute \[pmol/kg/min\]) of human insulin for up to 36 hours. IV infusion of sinistrin (250 mg/mL, SOC to achieve a steady state for up to 16 hours). |
| Insulin Peglispro/Insulin Glargine | EXPERIMENTAL | Insulin peglispro (LY2605541) administered to participants with T1DM subcutaneously (SQ) once daily (QD) for 28 to 35 days in one of two treatment periods. Dose is based on participant's prestudy basal insulin dosing regimen. Insulin glargine administered to participants with T1DM SQ QD for 28 to 35 days in one of two treatment periods. Dose is based on participant's prestudy basal insulin dosing regimen. Participants continue to use mealtime insulin. |
| Insulin Glargine/Insulin Peglispro | ACTIVE_COMPARATOR | Insulin glargine administered to participants with T1DM SQ QD for 28 to 35 days in one of two treatment periods. Dose is based on participant's prestudy basal insulin dosing regimen. Participants continue to use mealtime insulin. Insulin peglispro (LY2605541) administered to participants with T1DM subcutaneously (SQ) once daily (QD) for 28 to 35 days in one of two treatment periods. Dose is based on participant's prestudy basal insulin dosing regimen. |
| Control | NO_INTERVENTION | Control Arm. Untreated healthy participants. |
| LY2605541 (Part A) | EXPERIMENTAL | 0.5 units per kilogram (U/kg) LY2605541 subcutaneously (SC) once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14. Participants remained on their regular physician-prescribed mealtime insulin. |
| Glargine (Part A) | ACTIVE_COMPARATOR | 0.5 U/kg insulin glargine SC once daily for 15 days. Part A involved 3 clamp procedures on Days 8, 11, and 14. Participants remained on their regular physician-prescribed mealtime insulin. |
| First LY2605541 + Exercise,Then LY2605541 Alone (Part B) | EXPERIMENTAL | 0.5 U/kg LY2605541 SC once daily for an additional 6 days, beginning on Day 16. Exercise challenge on Day 17 (no exercise on Day 20).Participants remained on their regular physician-prescribed mealtime insulin. |
| First LY2605541 Alone, Then LY2605541 + Exercise (Part B) | EXPERIMENTAL | 0.5 U/kg LY2605541 SC once daily for an additional 6 days, beginning on Day 16. Exercise challenge on Day 20 (no exercise on Day 17). Participants remained on their regular physician-prescribed mealtime insulin. |
| First Glargine + Exercise, Then Glargine Alone (Part B) | ACTIVE_COMPARATOR | 0.5 U/kg insulin glargine SC once daily for an additional 6 days, beginning on Day 16. Exercise challenge on Day 17 (no exercise on Day 20). Participants remained on their regular physician-prescribed mealtime insulin. |
| First Glargine Alone, Then Glargine + Exercise (Part B) | ACTIVE_COMPARATOR | 0.5 U/kg insulin glargine SC once daily for an additional 6 days, beginning on Day 16. Exercise challenge on Day 20 (no exercise on Day 17). |
| LY2605541-Normal Hepatic Function | EXPERIMENTAL | Participants with normal hepatic function will receive a single subcutaneous (SC) dose of 0.075 milligrams per kilogram (mg/kg) LY2605541 |
| LY2605541-Mild Hepatic Impairment | EXPERIMENTAL | Participants with mild hepatic impairment will receive a single SC dose of 0.075 mg/kg LY2605541 |
| LY2605541-Moderate Hepatic Impairment | EXPERIMENTAL | Participants with moderate hepatic impairment will receive a single SC dose of 0.075 mg/kg LY2605541 |
| LY2605541-Severe Hepatic Impairment | EXPERIMENTAL | Participants with severe hepatic impairment will receive a single SC dose of 0.075 mg/kg LY2605541 |
| Part A, Cohort A; LY2605541 | EXPERIMENTAL | Healthy participants received 5.1 milliunits/minute (mU/min) in Period 1, 10.2 mU/min in Period 2, and 15.3 mU/min in Period 3, administered intravenously (IV) over 8 hours. All periods were separated by a minimum 6-day washout period |
| Part A, Cohort A; Insulin Glargine | ACTIVE_COMPARATOR | Healthy participants received insulin glargine (30 milliunits/meter squared/minute \[mU/m\^2/min\]) administered IV over 8 hours in Period 4. All periods were separated by a minimum 6-day washout period |
| Part A, Cohort B; LY2605541 | EXPERIMENTAL | Healthy participants received 15.3 mU/min in Period 1, 37.0 mU/min in Period 2, and 74.1 mU/min in Period 3, administered IV over 8 hours. All periods were separated by a minimum 6-day washout period. |
| Part A, Cohort B; Insulin Glargine | ACTIVE_COMPARATOR | Healthy participants received insulin glargine (60 mU/m\^2/min) administered IV over 8 hours in Period 4. All periods were separated by a minimum 6-day washout period. |
| Part B; LY2605541 | EXPERIMENTAL | Participants with T1DM received 15.3 mU/min in 1 of 4 study periods, administered IV up to 8 hours and received 74.1 mU/min in 1 of 4 Periods, administered IV up to 10 hours. Each dose was separated by a minimum 6-day washout period. |
| Part B; Insulin Glargine | ACTIVE_COMPARATOR | Participants with T1DM received 1 insulin glargine dose per study period (10 and 20 mU/m\^2/min) administered IV over 8 hours in 2 of 4 study periods. Each dose was separated by a minimum 6-day washout period. |
| Name | Type | Description |
|---|---|---|
| Insulin Peglispro | DRUG | Administered SQ |
| Insulin Glargine | DRUG | Administered SQ |
| Oral Antihyperglycemic Medications (OAMs) | DRUG | Administered orally |
| LY2605541 | DRUG | - |
| Human Insulin NPH | DRUG | - |
| Oral Antihyperglycemic Medications (OAM) | DRUG | - |
| Insulin Lispro | DRUG | All participants will be administering insulin lispro SQ as their pre-meal insulin during the course of the trial. |
| Human Insulin | DRUG | Administered IV |
Inclusion Criteria: * Have type 2 diabetes mellitus (T2DM), based on the World Health Organization (WHO) classification, for ≥1 year. * Use any type of basal insulin (except degludec), including once-or twice-daily human insulin neutral protamine Hagedom (NPH), insulin detemir, or insulin glargine....
LY2605541, also known as insulin peglispro, is an investigational insulin therapy developed by Eli Lilly and Company for the treatment of type 1 and type 2 diabetes mellitus. It was studied in Phase 3 clinical development as a long-acting basal insulin. All nine of its registered trials have been completed.
LY2605541 was studied for glycemic control in type 1 diabetes mellitus. Trials such as NCT02152384 in Germany and NCT02109029 in Austria compared insulin peglispro with insulin glargine and examined insulin concentrations in fat tissue. It is investigational and has not been approved for use.
Eli Lilly and Company, which trades on the New York Stock Exchange under the ticker LLY, developed LY2605541, also called insulin peglispro. The company sponsored the clinical program evaluating the drug in type 1 and type 2 diabetes mellitus.
LY2605541 reached Phase 3 clinical development, and all nine of its registered trials are completed with no active studies. It is an investigational drug and has not been approved by the FDA. The program included a Phase 3 trial, NCT02132637, in type 2 diabetes.
Nine completed trials studied LY2605541, enrolling about 3,280 participants. These include NCT02197520 and NCT02152384, which compared insulin peglispro with glargine on insulin sensitivity and mealtime insulin requirements, plus NCT02132637 and NCT02109029. No trials are currently active.
Yes, LY2605541 and insulin peglispro are two names for the same investigational drug. Eli Lilly and Company used the code LY2605541 during development, while insulin peglispro is the descriptive name. Both refer to the same basal insulin candidate studied in type 1 and type 2 diabetes.