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Study of Insulin Lispro in Participants With Inadequately Controlled Type 2 Diabetes (AUTONOMY)

Primary Purpose

Diabetes Mellitus, Type 2

Status

Completed

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

Insulin lispro

Glargine

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2 focused on measuring Type 2 Diabetes, Insulin, Algorithms, Blood glucose levels

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Have type 2 diabetes
Have been treated for at least 90 days with insulin glargine, neutral protamine Hagedorn (NPH), or detemir in combination with oral antihyperglycemic agents as monotherapy, dual, or triple therapy [sulfonylurea, meglitinide, metformin, pioglitazone, or dipeptidyl peptidase-4 (DPP-4) inhibitor] and in the opinion of the investigator requires further intensification of therapy
Are treated with insulin glargine, NPH, or detemir at least 20 units per day (U/day) at enrollment
Have an glycated hemoglobin (HbA1c) value greater than 7.0% and less than or equal to 12.0% according to the central laboratory at screening
Capable of and willing to do the following: inject insulin with a prefilled pen, perform self blood glucose monitoring and record keeping as required by this protocol, as determined by the investigator
Have given written informed consent to participate in this study in accordance with local regulations

Exclusion Criteria:

Prior rapid- or short-acting insulin therapy: participants receiving scheduled long-term short-acting or rapid-acting or premixed insulin therapy within the past 6 months will not be eligible to participate in the study. Participants who have previously received short- or rapid-acting insulin as part of short-term insulin therapy (during gestational diabetes, during an acute hospitalization or illness) or occasional use will be allowed to participate in this study. Occasional use (e.g., used to treat acute hyperglycemia) shall be defined as less than daily administration of not more than 1 dose per day of short- or rapid-acting insulin
Concomitant medications: glucagon-like peptide-1 (GLP-1) receptor agonist, alpha-glucosidase inhibitor, or rosiglitazone use concurrently or within 3 months prior to entry into the study
Severe hypoglycemia: have had more than one episode of severe hypoglycemia (defined as requiring assistance of a third party due to disabling hypoglycemia) within 6 months prior to entry into the study
Excessive insulin resistance: received a total daily dose of insulin greater than 2.0 units per kilogram (U/kg) at the time of randomization
Morbid obesity: defined as a body mass index greater than or equal to 45 kilograms per square meter (kg/m²)
Malignancy: have active or untreated malignancy, or have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer) for less than 5 years
Cardiovascular: have cardiac disease with functional status that is New York Heart Association Class III or IV (see New York Heart Association Cardiac Disease Classifications) or have Congestive Heart Failure (CHF) requiring pharmacologic treatment or, in the investigator's opinion, have severe dependent edema (i.e., edema of the feet or ankles) or have any condition associated with hypoperfusion, hypoxemia, dehydration, or sepsis
Renal: have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine greater than or equal to 2 milligrams per deciliter (mg/dL) if not on metformin
Hepatic: have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) greater than 3 times the upper limit of the reference range as defined by the central laboratory
Hematologic: have known hemoglobinopathy or chronic anemia or other known blood disorder
Reproductive:(for women) are pregnant or intend to become pregnant during the course of the study; are sexually active women of childbearing potential not actively practicing birth control by a method determined by the investigator to be medically acceptable; or are breastfeeding
Allergy: have known allergy to insulin lispro, insulin glargine, or excipients contained in these products
Glucocorticoid therapy: receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks immediately before screening
Adherence to protocol: have any other condition (including known drug or alcohol abuse or psychiatric disorder) that precludes the participant from following and completing the protocol
Prior participation: are currently enrolled in, or have participated in, an interventional medical, surgical, or pharmaceutical drug or device or off-label use study (an investigational study in which a medical or surgical treatment was given) within 30 days prior to entry into the study, or persons who have previously completed or withdrawn from this study (after having signed the informed consent document). Participants may be ineligible if they are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
Non-approved drug: have been treated with a drug within the last 30 days that has not received regulatory approval at the time of study entry

Sites / Locations

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

3 Day Algorithm

Daily Algorithm

Arm Description

Basal insulin glargine plus mealtime bolus insulin lispro titrated based on blood glucose readings from the past three days. (Sites were assigned to Study A and Study B according to an allocation plan that was pre-specified before initiation of Study A and Study B)

Basal insulin glargine plus mealtime bolus insulin lispro titrated based on blood glucose readings from the previous day. (Sites were assigned to Study A and Study B according to an allocation plan that was pre-specified before initiation of Study A and Study B)

Outcomes

Primary Outcome Measures

Change From Baseline to 24 Week Endpoint in Glycated Hemoglobin (HbA1c)

The change from baseline to 24 weeks in the percentage of HbA1c in plasma. The Least Squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included the independent variables: fixed effects for treatment, country, sulfonylurea/meglitinide use, visit, treatment by visit interaction with baseline HbA1c as a covariate.

Secondary Outcome Measures

Percentage of Participants Achieving Glycated Hemoglobin (HbA1c) Target Values

Percentage of participants who achieved HbA1c levels of ≤7.0% or ≤6.5%.

Percentage of Participants ≥65 Years of Age Achieving Glycated Hemoglobin (HbA1c) Target Concentration

Percentage of participants ≥65 years of age achieving HbA1c target concentration of ≤7.0% or ≤6.5%.

Change From Baseline to 24 Week Endpoint in Body Weight

Body weight was measured twice at each indicated visit and the average of the 2 measurements was used for analyses. Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and >8%), visit and treatment-by-visit interaction .

Time to Reach Glycated Hemoglobin (HbA1c) Target Values

Percentage of participants is the number of participants who achieved HbA1c target values of ≤6.5% or ≤7.0% during the specified time period divided by the total number of participants who did not discontinue from the study but had not reached HbA1c target at the beginning of the specified post baseline time period (≤100 days and ≥101 days). Participants who did not experience an outcome before discontinuation or completion of the study were censored using the date of discontinuation. Participants who were lost to follow up the date of discontinuation were considered to be the date of last contact.

Change From Baseline to 24 Week Endpoint in Fasting Glucose

Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and >8%), visit and treatment-by-visit interaction.

Change From Baseline to 24 Week Endpoint in Fasting Glucose in Participants ≥65 Years of Age

Change From Baseline to 24 Week Endpoint in 1,5-anhydroglucitol (1,5-AG)

Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and >8%), visit and treatment-by-visit interaction.

Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile

7-Point Self-Monitored Blood Glucose profiles are measures of blood glucose concentration taken 7 time a day at the morning pre-meal, morning 2-hours (HR) postprandial (PP), midday pre-meal, midday 2-hours post-meal, evening pre-meal, bedtime and 0300 hour (3 am). Each participant took measures over any 3 days and the average was calculated for each of the 7 time points. Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and >8%), visit and treatment-by-visit interaction.

Daily Dose of Insulin: Total, Basal and Prandial (Bolus)

Total insulin was the sum of basal insulin (glargine) that was required to manage normal daily blood fluctuations and prandial insulin that was taken at meal time. Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and >8%), visit and treatment-by-visit interaction.

Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial (Bolus)

Total insulin was the sum of basal insulin (glargine) that was required to manage normal daily blood fluctuations and prandial insulin that was taken at meal time. Total, basal and prandial amounts were then divided by the participant's body weight in kilograms (kg). Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and >8%), visit and treatment-by-visit interaction.

The Number of Participants With a Hypoglycemic Episode (Incidence)

A hypoglycemic episode was defined as any time a participant felt they were experiencing a sign or symptom that was associated with hypoglycemia, or had a blood glucose level of ≤70 milligram per deciliter [mg/dL, ≤3.9 millimoles per liter (mmol/L)] even if it was not associated with signs, symptoms or treatment (consistent with current American Diabetes Association 2005 guidelines).

The Number of Participants ≥65 Years of Age With Hypoglycemic Episodes (Incidence)

A hypoglycemic episode in participants ≥ 65 years of age was defined as any time a participant felt they were experiencing a sign or symptom that was associated with hypoglycemia, or had a blood glucose level of ≤70 milligram per deciliter [mg/dL, ≤3.9 millimoles per liter (mmol/L)] even if it was not associated with signs, symptoms or treatment (consistent with current American Diabetes Association 2005 guidelines).

The Rate of Hypoglycemic Episodes

The hypoglycemia rate per 30 days was calculated as the number of hypoglycemic episodes reported divided by the number of days at risk times 30.

Percentage of Participants With Severe Hypoglycemic Episodes

Severe hypoglycemia is defined as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. Plasma glucose measurements may not be available during such an event, but neurological recovery attributable to the restoration of plasma glucose to normal is considered sufficient evidence that the event was induced by low plasma glucose.

Full Information

NCT ID

NCT01215955

First Posted

September 30, 2010

Last Updated

April 3, 2014

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT01215955

Brief Title

Study of Insulin Lispro in Participants With Inadequately Controlled Type 2 Diabetes

Acronym

AUTONOMY

Official Title

Two Approaches to Escalate Lispro Therapy in Patients With Type 2 Diabetes Mellitus Not Achieving Adequate Glycemic Control on Basal Insulin Therapy and Oral Agents Alone (AUTONOMY)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2014

Overall Recruitment Status

Completed

Study Start Date

December 2010 (undefined)

Primary Completion Date

January 2013 (Actual)

Study Completion Date

January 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Evidence regarding optimal methods of insulin dose adjustment is lacking in the literature. The purpose of this study is to evaluate the efficacy and safety of two approaches to escalate prandial insulin therapy in participants with type 2 diabetes mellitus not achieving adequate glycemic control on basal insulin.

Detailed Description

Participants who enter the study and are already taking insulin glargine with a screening HbA1c >7.0% will be randomized to one of two treatment arms. Both arms will add prandial insulin to existing basal insulin therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Type 2

Keywords

Type 2 Diabetes, Insulin, Algorithms, Blood glucose levels

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

1117 (Actual)

8. Arms, Groups, and Interventions

Arm Title

3 Day Algorithm

Arm Type

Experimental

Arm Description

Arm Title

Daily Algorithm

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Insulin lispro

Other Intervention Name(s)

Humalog, LY275585

Intervention Description

Administered subcutaneously, up to three times daily for 24 weeks

Intervention Type

Drug

Intervention Name(s)

Glargine

Intervention Description

Administered subcutaneously, dosage determined by investigator once daily for 24 weeks

Primary Outcome Measure Information:

Title

Change From Baseline to 24 Week Endpoint in Glycated Hemoglobin (HbA1c)

Description

Time Frame

Baseline, 24 weeks

Secondary Outcome Measure Information:

Title

Percentage of Participants Achieving Glycated Hemoglobin (HbA1c) Target Values

Description

Percentage of participants who achieved HbA1c levels of ≤7.0% or ≤6.5%.

Time Frame

24-week endpoint

Title

Percentage of Participants ≥65 Years of Age Achieving Glycated Hemoglobin (HbA1c) Target Concentration

Description

Percentage of participants ≥65 years of age achieving HbA1c target concentration of ≤7.0% or ≤6.5%.

Time Frame

24-week endpoint

Title

Change From Baseline to 24 Week Endpoint in Body Weight

Description

Time Frame

Baseline, 24-weeks

Title

Time to Reach Glycated Hemoglobin (HbA1c) Target Values

Description

Time Frame

Baseline through 24 weeks

Title

Change From Baseline to 24 Week Endpoint in Fasting Glucose

Description

Time Frame

Baseline, 24 weeks

Title

Change From Baseline to 24 Week Endpoint in Fasting Glucose in Participants ≥65 Years of Age

Description

Time Frame

Baseline, 24 weeks

Title

Change From Baseline to 24 Week Endpoint in 1,5-anhydroglucitol (1,5-AG)

Description

Time Frame

Baseline, 24 weeks

Title

Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile

Description

Time Frame

Baseline, 24 weeks

Title

Daily Dose of Insulin: Total, Basal and Prandial (Bolus)

Description

Time Frame

24 weeks

Title

Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial (Bolus)

Description

Time Frame

24 weeks

Title

The Number of Participants With a Hypoglycemic Episode (Incidence)

Description

Time Frame

Randomization through 24 weeks overall

Title

The Number of Participants ≥65 Years of Age With Hypoglycemic Episodes (Incidence)

Description

Time Frame

Randomization through 24 weeks overall

Title

The Rate of Hypoglycemic Episodes

Description

The hypoglycemia rate per 30 days was calculated as the number of hypoglycemic episodes reported divided by the number of days at risk times 30.

Time Frame

Randomization through 24 weeks overall

Title

Percentage of Participants With Severe Hypoglycemic Episodes

Description

Time Frame

Randomization up to 24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Have type 2 diabetes Have been treated for at least 90 days with insulin glargine, neutral protamine Hagedorn (NPH), or detemir in combination with oral antihyperglycemic agents as monotherapy, dual, or triple therapy [sulfonylurea, meglitinide, metformin, pioglitazone, or dipeptidyl peptidase-4 (DPP-4) inhibitor] and in the opinion of the investigator requires further intensification of therapy Are treated with insulin glargine, NPH, or detemir at least 20 units per day (U/day) at enrollment Have an glycated hemoglobin (HbA1c) value greater than 7.0% and less than or equal to 12.0% according to the central laboratory at screening Capable of and willing to do the following: inject insulin with a prefilled pen, perform self blood glucose monitoring and record keeping as required by this protocol, as determined by the investigator Have given written informed consent to participate in this study in accordance with local regulations Exclusion Criteria: Prior rapid- or short-acting insulin therapy: participants receiving scheduled long-term short-acting or rapid-acting or premixed insulin therapy within the past 6 months will not be eligible to participate in the study. Participants who have previously received short- or rapid-acting insulin as part of short-term insulin therapy (during gestational diabetes, during an acute hospitalization or illness) or occasional use will be allowed to participate in this study. Occasional use (e.g., used to treat acute hyperglycemia) shall be defined as less than daily administration of not more than 1 dose per day of short- or rapid-acting insulin Concomitant medications: glucagon-like peptide-1 (GLP-1) receptor agonist, alpha-glucosidase inhibitor, or rosiglitazone use concurrently or within 3 months prior to entry into the study Severe hypoglycemia: have had more than one episode of severe hypoglycemia (defined as requiring assistance of a third party due to disabling hypoglycemia) within 6 months prior to entry into the study Excessive insulin resistance: received a total daily dose of insulin greater than 2.0 units per kilogram (U/kg) at the time of randomization Morbid obesity: defined as a body mass index greater than or equal to 45 kilograms per square meter (kg/m²) Malignancy: have active or untreated malignancy, or have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer) for less than 5 years Cardiovascular: have cardiac disease with functional status that is New York Heart Association Class III or IV (see New York Heart Association Cardiac Disease Classifications) or have Congestive Heart Failure (CHF) requiring pharmacologic treatment or, in the investigator's opinion, have severe dependent edema (i.e., edema of the feet or ankles) or have any condition associated with hypoperfusion, hypoxemia, dehydration, or sepsis Renal: have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine greater than or equal to 2 milligrams per deciliter (mg/dL) if not on metformin Hepatic: have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) greater than 3 times the upper limit of the reference range as defined by the central laboratory Hematologic: have known hemoglobinopathy or chronic anemia or other known blood disorder Reproductive:(for women) are pregnant or intend to become pregnant during the course of the study; are sexually active women of childbearing potential not actively practicing birth control by a method determined by the investigator to be medically acceptable; or are breastfeeding Allergy: have known allergy to insulin lispro, insulin glargine, or excipients contained in these products Glucocorticoid therapy: receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks immediately before screening Adherence to protocol: have any other condition (including known drug or alcohol abuse or psychiatric disorder) that precludes the participant from following and completing the protocol Prior participation: are currently enrolled in, or have participated in, an interventional medical, surgical, or pharmaceutical drug or device or off-label use study (an investigational study in which a medical or surgical treatment was given) within 30 days prior to entry into the study, or persons who have previously completed or withdrawn from this study (after having signed the informed consent document). Participants may be ineligible if they are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study Non-approved drug: have been treated with a drug within the last 30 days that has not received regulatory approval at the time of study entry

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

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)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85050

Country

United States

Facility Name

City

Concord

State/Province

California

ZIP/Postal Code

94520

Country

United States

Facility Name

City

Fresno

State/Province

California

ZIP/Postal Code

93720

Country

United States

Facility Name

City

Lakewood

State/Province

California

ZIP/Postal Code

90712

Country

United States

Facility Name

City

Lancaster

State/Province

California

ZIP/Postal Code

93534

Country

United States

Facility Name

City

Mission Hills

State/Province

California

ZIP/Postal Code

91345

Country

United States

Facility Name

City

Tustin

State/Province

California

ZIP/Postal Code

92780

Country

United States

Facility Name

City

Bradenton

State/Province

Florida

ZIP/Postal Code

34208

Country

United States

Facility Name

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32209

Country

United States

Facility Name

City

Orlando

State/Province

Florida

ZIP/Postal Code

32806

Country

United States

Facility Name

City

Pembroke Pines

State/Province

Florida

ZIP/Postal Code

33027

Country

United States

Facility Name

City

Idaho Falls

State/Province

Idaho

ZIP/Postal Code

83404

Country

United States

Facility Name

City

Lewiston

State/Province

Idaho

ZIP/Postal Code

83501

Country

United States

Facility Name

City

Evansville

State/Province

Indiana

ZIP/Postal Code

47714

Country

United States

Facility Name

City

Des Moines

State/Province

Iowa

ZIP/Postal Code

50314

Country

United States

Facility Name

City

Topeka

State/Province

Kansas

ZIP/Postal Code

66606

Country

United States

Facility Name

City

Lexington

State/Province

Kentucky

ZIP/Postal Code

40503

Country

United States

Facility Name

City

Metairie

State/Province

Louisiana

ZIP/Postal Code

70006

Country

United States

Facility Name

City

Shreveport

State/Province

Louisiana

ZIP/Postal Code

71106

Country

United States

Facility Name

City

Haverhill

State/Province

Massachusetts

ZIP/Postal Code

01830

Country

United States

Facility Name

City

Troy

State/Province

Michigan

ZIP/Postal Code

48085

Country

United States

Facility Name

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55416

Country

United States

Facility Name

City

Clarkson Valley

State/Province

Missouri

ZIP/Postal Code

63011

Country

United States

Facility Name

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89119

Country

United States

Facility Name

City

Flemington

State/Province

New Jersey

ZIP/Postal Code

08822

Country

United States

Facility Name

City

Syracuse

State/Province

New York

ZIP/Postal Code

13210

Country

United States

Facility Name

City

Dayton

State/Province

Ohio

ZIP/Postal Code

45439

Country

United States

Facility Name

City

Portland

State/Province

Oregon

ZIP/Postal Code

97210

Country

United States

Facility Name

City

Beaver

State/Province

Pennsylvania

ZIP/Postal Code

15009

Country

United States

Facility Name

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19107

Country

United States

Facility Name

City

Dallas

State/Province

Texas

ZIP/Postal Code

75231

Country

United States

Facility Name

City

Houston

State/Province

Texas

ZIP/Postal Code

77095

Country

United States

Facility Name

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Facility Name

City

Buenos Aires

ZIP/Postal Code

C1425AGC

Country

Argentina

Facility Name

City

Mar Del Plata

ZIP/Postal Code

B7600FZN

Country

Argentina

Facility Name

City

Rosario

ZIP/Postal Code

2000

Country

Argentina

Facility Name

City

Vienna

ZIP/Postal Code

1130

Country

Austria

Facility Name

City

Belem

ZIP/Postal Code

66073-000

Country

Brazil

Facility Name

City

Curitiba

ZIP/Postal Code

80060-900

Country

Brazil

Facility Name

City

Maringa

ZIP/Postal Code

87015-320

Country

Brazil

Facility Name

City

Winnipeg

State/Province

Manitoba

ZIP/Postal Code

R3E 3P4

Country

Canada

Facility Name

City

Charlottetown

State/Province

Prince Edward Island

ZIP/Postal Code

C1A 1L2

Country

Canada

Facility Name

City

Sherbrooke

State/Province

Quebec

ZIP/Postal Code

J1G 2E9

Country

Canada

Facility Name

City

Osijek

ZIP/Postal Code

31000

Country

Croatia

Facility Name

City

Slavonski Brod

ZIP/Postal Code

35 000

Country

Croatia

Facility Name

City

Zagreb

ZIP/Postal Code

10000

Country

Croatia

Facility Name

City

Frederiksberg

ZIP/Postal Code

2000

Country

Denmark

Facility Name

City

Kobenhavn

ZIP/Postal Code

2400

Country

Denmark

Facility Name

City

Kolding

ZIP/Postal Code

6000

Country

Denmark

Facility Name

City

Bourges

ZIP/Postal Code

18000

Country

France

Facility Name

City

La Bouexiere

ZIP/Postal Code

35340

Country

France

Facility Name

City

Nantes

ZIP/Postal Code

44300

Country

France

Facility Name

City

Kaunas

ZIP/Postal Code

LT-51270

Country

Lithuania

Facility Name

City

Raseiniai

ZIP/Postal Code

60127

Country

Lithuania

Facility Name

City

Ukmerge

ZIP/Postal Code

20184

Country

Lithuania

Facility Name

City

Cuauhtemoc

ZIP/Postal Code

06090

Country

Mexico

Facility Name

City

Guadalajara Jalisco

ZIP/Postal Code

04460

Country

Mexico

Facility Name

City

Guadalajara

ZIP/Postal Code

44150

Country

Mexico

Facility Name

City

Mexico City

ZIP/Postal Code

03300

Country

Mexico

Facility Name

City

Monterrey

ZIP/Postal Code

64710

Country

Mexico

Facility Name

City

Lodz

ZIP/Postal Code

90-242

Country

Poland

Facility Name

City

Lublin

ZIP/Postal Code

20-538

Country

Poland

Facility Name

City

Poznan

ZIP/Postal Code

61-655

Country

Poland

Facility Name

City

Szczecin

ZIP/Postal Code

70-506

Country

Poland

Facility Name

City

Caguas

ZIP/Postal Code

00726

Country

Puerto Rico

Facility Name

City

Manati

ZIP/Postal Code

00674

Country

Puerto Rico

Facility Name

City

Ponce

ZIP/Postal Code

007171563

Country

Puerto Rico

Facility Name

City

Rio Piedras

ZIP/Postal Code

00921

Country

Puerto Rico

Facility Name

City

San Juan

ZIP/Postal Code

00917

Country

Puerto Rico

Facility Name

City

Bucharest

ZIP/Postal Code

022441

Country

Romania

Facility Name

City

Oradea

ZIP/Postal Code

410169

Country

Romania

Facility Name

City

Saint Petersburg

ZIP/Postal Code

197022

Country

Russian Federation

Facility Name

City

Saratov

ZIP/Postal Code

410053

Country

Russian Federation

Facility Name

City

Stavropol

ZIP/Postal Code

355035

Country

Russian Federation

Facility Name

City

Halfway House

ZIP/Postal Code

1685

Country

South Africa

Facility Name

City

Somerset West

ZIP/Postal Code

7130

Country

South Africa

12. IPD Sharing Statement

Learn more about this trial

Study of Insulin Lispro in Participants With Inadequately Controlled Type 2 Diabetes

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