Basal-Plus: Basal Bolus Versus Basal Insulin in Type 2 Diabetes Mellitus (T2DM)
Study Details
Study Description
Brief Summary
The study is a prospective randomized study comparing safety and effectiveness of a basal-bolus regimen with glargine once daily and glulisine before meals, a basal plus regimen with glargine once daily and supplemental doses of glulisine, and sliding scale regular insulin (SSI) on correction of insulin regimen for the hospital management of medical and surgical patients with type 2 diabetes.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
High blood glucose levels in medical and surgery patients with diabetes are associated with increased risk of in-hospital complications and death. Improved glucose control with insulin injections may improve clinical outcome and prevent some of the hospital complications. Numerous studies have shown that high blood glucose increases the risk of wound infection, kidney failure and death. It is not known; however, what is the best insulin regimen in patients who will undergo surgery. The use of repeated injections of regular insulin is commonly used for glucose control in hospitalized patients with diabetes. Recently, the combination of Lantus® and Apidra® insulins has been shown to improve glucose control with lower rate of hypoglycemia (low blood sugar). The investigators' recent preliminary data also indicate that a single daily dose of glargine plus corrective doses of glulisine before meals if needed (Basal Plus) is effective in the management of medical and surgical patients with type 2 diabetes mellitus (T2DM). The average daily blood glucose (BG) levels in patients treated with Basal Plus is equivalent to levels in patients treated with Basal Bolus with glargine once daily plus glulisine before meals (basal bolus regimen). The mean daily BG levels in patients treated with basal plus are lower than those reported in patients treated with sliding scale regular insulin (SSRI). Accordingly, the present study aims to determine which insulin treatment is best for glucose control in hospitalized patients with diabetes admitted to general medicine wards. Glargine, glulisine, and regular insulins are approved for use in the treatment of patients with diabetes by the FDA. A total of 375 subjects with type 2 diabetes will be recruited in this study. The sites for this study are Grady Memorial Hospital, Emory University Hospital, the Atlanta VA Medical Center, Scott & White Memorial Hospital and Clinic, and Medical University of South Carolina.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Basal Plus Regimen glargine subcutaneously once daily plus corrective doses of glulisine subcutaneously before meals and bedtime as needed |
Drug: Basal Plus
glargine once daily plus corrective doses of glulisine before meals and bedtime as needed
Other Names:
|
| Experimental: Basal Bolus glargine subcutaneously once daily plus glulisine subcutaneously before meals (plus corrective doses of glulisine as needed) |
Drug: Basal Bolus
glargine once daily plus glulisine before meals (plus corrective doses of glulisine as needed)
Other Names:
|
| Active Comparator: sliding scale regular insulin (SSRI) sliding scale regular insulin subcutaneously four-times daily in patients with T2DM admitted to general medicine and surgery wards. |
Drug: sliding scale regular insulin (SSRI)
four-time daily in patients with T2DM admitted to general medicine and surgery wards.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Mean Blood Glucose Levels (Measured in mg/dL) at Randomization Are Compared to Mean Blood Glucose Levels After First Day of Treatment Among Subjects Treated With Basal Plus, Basal -Bolus and SSRI Treatments [Randomization and 24 hrs after treatment]
The primary outcome is to determine the effective glycemic control among the subjects that received Basal Plus (glargine once daily plus corrective doses of glulisine before meals and bedtime as needed), Basal Bolus approach of glargine once daily plus corrective doses of glulisine before meals and Sliding Scale Regular Insulin (SSRI). Glycemic control is measured by mean blood glucose(BG) levels in mg/dL after first day of treatment and are compared to mean BG levels at randomization among subjects treated with Basal Plus, Basal -bolus and SSRI treatments. The optimal glycemic control is achieved when BG levels are between 70 mg/dL -140 mg/dL. The BG levels levels below 70 mg/dL are regarded as hypoglycemic events. The BG levels levels above 140 mg/dl are considered elevated and Hyperglycemia defined as a fasting BG >126 mg/dl or random BG >200 mg/dl on two or more occasions).
Secondary Outcome Measures
- Number of Patients With Hypoglycemia Events (Blood Glucose Levels < 70 mg/dL) During Their Hospital Stay That Are Treated With Basal Plus, Basal-bolus and SSRI Treatments [During hospital stay, up to 12 days]
Effective Glycemic control is also assessed by number of hypoglycemia events among the patients treated with Basal plus, basal-bolus and SSRI treatments. Hypoglycemia event is defined as blood glucose levels <70 mg/dL. Number of patients with hypoglycemia episodes that are treated with Basal plus, basal-bolus and SSRI treatment regimens during their hospital stay are examined and compared.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Males or females between the ages of 18 and 75 years admitted to a general medicine or surgical services.
-
A known history of type 2 diabetes mellitus > 3 months, receiving either diet alone, oral monotherapy, or with any combination of oral antidiabetic agents (sulfonylureas, meglitinides, metformin, thiazolidinediones, dipeptidyl peptidase (DPP) IV inhibitors).
-
Patients admitted for non-cardiac elective or emergency surgery or trauma.
-
Subjects must have an admission BG > 140 mg and < 400 mg/dL without laboratory evidence of diabetic ketoacidosis (bicarbonate < 18 milliequivalent /L, potential hydrogen (pH) < 7.30, or positive serum or urinary ketones).
Exclusion Criteria:
-
Subjects with increased blood glucose concentration, but without a known history of diabetes (stress hyperglycemia).
-
Subjects with a history of diabetic ketoacidosis and hyperosmolar hyperglycemic state, or ketonuria [32].
-
Patients with acute critical or surgical illness admitted to the ICU or expected to require admission to the ICU.
-
Patients admitted for coronary artery bypass graft (CABG) or patients receiving continuous insulin infusion.
-
Patients with clinically relevant hepatic disease (diagnosed liver cirrhosis and portal hypertension), corticosteroid therapy, or impaired renal function (creatinine ≥ 3.0 mg/dl).
-
Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study.
-
Female subjects are pregnant or breast feeding at time of enrollment into the study.
-
Patients with recognized or suspected endocrine disorders associated with increased insulin resistance, acromegaly, or hyperthyroidism.
-
Female subjects are pregnant or breast feeding at time of enrollment into the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Grady Memorial Hospital | Atlanta | Georgia | United States | 30303 |
| 2 | Emory University Hospital | Atlanta | Georgia | United States | 30322 |
| 3 | Atlanta VA Medical Center | Decatur | Georgia | United States | 30030 |
| 4 | Medical University of South Carolina | Charleston | South Carolina | United States | 29425-6240 |
| 5 | Scott & White Memorial Hospital and Clinic | Temple | Texas | United States | 76508 |
Sponsors and Collaborators
- Guillermo Umpierrez, MD
- Sanofi
- Medical University of South Carolina
- Texas A&M University
Investigators
- Principal Investigator: Guillermo Umpierrez, MD, Emory SOM
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB00020328a
Study Results
Participant Flow
| Recruitment Details | 375 subjects were enrolled in the study from January 2010 to June 2012. The study is conducted in 3 states and patients were enrolled from 3 hospitals in state of Georgia; 1 hospitals in south Carolina and 1 hospitals in Texas. |
|---|---|
| Pre-assignment Detail | 24 subjects that were consented were withdrawn from the study and not included in analysis because they meet exclusion criteria like transferring to ICU; receiving treatment < 24 hrs and for receiving steroids |
| Arm/Group Title | Basal Bolus | Basal Plus Regimen | Sliding Scale Regular Insulin (SSRI) |
|---|---|---|---|
| Arm/Group Description | glargine once daily plus glulisine before meals (plus corrective doses of glulisine as needed) Basal Bolus : glargine once daily plus glulisine before meals (plus corrective doses of glulisine as needed) | glargine once daily plus corrective doses of glulisine before meals and bedtime as needed Basal Plus : glargine once daily plus corrective doses of glulisine before meals and bedtime as needed | four-time daily in patients with T2DM admitted to general medicine and surgery wards. sliding scale regular insulin (SSRI) : four-time daily in patients with T2DM admitted to general medicine and surgery wards. |
| Period Title: Overall Study | |||
| STARTED | 153 | 142 | 80 |
| COMPLETED | 144 | 133 | 74 |
| NOT COMPLETED | 9 | 9 | 6 |
Baseline Characteristics
| Arm/Group Title | Basal Bolus | Basal Plus Regimen | Sliding Scale Regular Insulin (SSRI) | Total |
|---|---|---|---|---|
| Arm/Group Description | glargine once daily plus glulisine before meals (plus corrective doses of glulisine as needed) Basal Bolus : glargine once daily plus glulisine before meals subcut at an initial dose of 0.3-0.5 units/kg/day (plus corrective doses of glulisine as needed) | glargine once daily plus corrective doses of glulisine before meals and bedtime as needed Basal Plus : glargine once daily subcut at an initial dose of 0.15-0.25 units/kg/day plus corrective doses of glulisine subcut before meals and bedtime as needed | four-time daily in patients with T2DM admitted to general medicine and surgery wards. sliding scale regular insulin (SSRI) given subcut four-times daily before meals and at bedtime | Total of all reporting groups |
| Overall Participants | 153 | 142 | 80 | 375 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
58.7
(11)
|
58.6
(13)
|
58.7
(12)
|
58.6
(12)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
62
40.5%
|
65
45.8%
|
33
41.3%
|
160
42.7%
|
| Male |
91
59.5%
|
77
54.2%
|
47
58.8%
|
215
57.3%
|
Outcome Measures
| Title | Mean Blood Glucose Levels (Measured in mg/dL) at Randomization Are Compared to Mean Blood Glucose Levels After First Day of Treatment Among Subjects Treated With Basal Plus, Basal -Bolus and SSRI Treatments |
|---|---|
| Description | The primary outcome is to determine the effective glycemic control among the subjects that received Basal Plus (glargine once daily plus corrective doses of glulisine before meals and bedtime as needed), Basal Bolus approach of glargine once daily plus corrective doses of glulisine before meals and Sliding Scale Regular Insulin (SSRI). Glycemic control is measured by mean blood glucose(BG) levels in mg/dL after first day of treatment and are compared to mean BG levels at randomization among subjects treated with Basal Plus, Basal -bolus and SSRI treatments. The optimal glycemic control is achieved when BG levels are between 70 mg/dL -140 mg/dL. The BG levels levels below 70 mg/dL are regarded as hypoglycemic events. The BG levels levels above 140 mg/dl are considered elevated and Hyperglycemia defined as a fasting BG >126 mg/dl or random BG >200 mg/dl on two or more occasions). |
| Time Frame | Randomization and 24 hrs after treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Basal Plus Regimen | Basal Bolus | Sliding Scale Regular Insulin (SSRI) |
|---|---|---|---|
| Arm/Group Description | glargine once daily plus corrective doses of glulisine before meals and bedtime as needed Basal Plus: glargine once daily plus corrective doses of glulisine before meals and bedtime as needed | glargine once daily plus glulisine before meals (plus corrective doses of glulisine as needed) Basal Bolus: glargine once daily plus glulisine before meals (plus corrective doses of glulisine as needed) | four-time daily in patients with type 2 diabetes mellitus (T2DM) admitted to general medicine and surgery wards. sliding scale regular insulin (SSRI): four-time daily in patients with T2DM admitted to general medicine and surgery wards. |
| Measure Participants | 133 | 144 | 74 |
| Randomization |
194
(45)
|
200
(49)
|
187
(43)
|
| After first day of therapy |
163
(37)
|
156
(36)
|
172
(41)
|
| Title | Number of Patients With Hypoglycemia Events (Blood Glucose Levels < 70 mg/dL) During Their Hospital Stay That Are Treated With Basal Plus, Basal-bolus and SSRI Treatments |
|---|---|
| Description | Effective Glycemic control is also assessed by number of hypoglycemia events among the patients treated with Basal plus, basal-bolus and SSRI treatments. Hypoglycemia event is defined as blood glucose levels <70 mg/dL. Number of patients with hypoglycemia episodes that are treated with Basal plus, basal-bolus and SSRI treatment regimens during their hospital stay are examined and compared. |
| Time Frame | During hospital stay, up to 12 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Basal Bolus | Basal Plus Regimen | Sliding Scale Regular Insulin (SSRI) |
|---|---|---|---|
| Arm/Group Description | glargine once daily plus glulisine before meals (plus corrective doses of glulisine as needed) Basal Bolus : glargine once daily plus glulisine before meals subcut at an initial dose of 0.3-0.5 units/kg/day (plus corrective doses of glulisine as needed) | glargine once daily plus corrective doses of glulisine before meals and bedtime as needed Basal Plus : glargine once daily subcut at an initial dose of 0.15-0.25 units/kg/day plus corrective doses of glulisine subcut before meals and bedtime as needed | four-time daily in patients with T2DM admitted to general medicine and surgery wards. sliding scale regular insulin (SSRI) given subcut four-times daily before meals and at bedtime |
| Measure Participants | 144 | 133 | 74 |
| Number [participants] |
23
15%
|
17
12%
|
2
2.5%
|
Adverse Events
| Time Frame | The time frame for the study is the duration of hospital stay of the patients. Among the study patients the mean (standard deviation) hospital stay for Basal bolus patients was 5.9 (5) days; Basal plus patients was 6(6) days; SSRI patients was 5.5(5) days. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Subjects were followed daily by the investigators for complications and mortality. But the study end points on adverse events are related to blood glucose (BG) levels. Hypoglycemia is defined as BG levels of < 70 mg/dL. Severe hypoglycemia is defined as blood glucose levels of < 40 mg/dL. Inpatient hyperglycemia defined as a fasting BG >126 mg/dl or random BG >200 mg/dl on two or more occasions. | |||||
| Arm/Group Title | Basal Plus Regimen | Basal Bolus | Sliding Scale Regular Insulin (SSRI) | |||
| Arm/Group Description | glargine once daily plus corrective doses of glulisine before meals and bedtime as needed Basal Plus: glargine once daily plus corrective doses of glulisine before meals and bedtime as needed | glargine once daily plus glulisine before meals (plus corrective doses of glulisine as needed) Basal Bolus: glargine once daily plus glulisine before meals (plus corrective doses of glulisine as needed) | four-time daily in patients with T2DM admitted to general medicine and surgery wards. sliding scale regular insulin (SSRI): four-time daily in patients with T2DM admitted to general medicine and surgery wards. | |||
All Cause Mortality |
||||||
| Basal Plus Regimen | Basal Bolus | Sliding Scale Regular Insulin (SSRI) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/133 (2.3%) | 0/144 (0%) | 0/74 (0%) | |||
Serious Adverse Events |
||||||
| Basal Plus Regimen | Basal Bolus | Sliding Scale Regular Insulin (SSRI) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 18/133 (13.5%) | 22/144 (15.3%) | 7/74 (9.5%) | |||
| Infections and infestations | ||||||
| wound infections | 3/133 (2.3%) | 1/144 (0.7%) | 1/74 (1.4%) | |||
| Bacteremia | 4/133 (3%) | 7/144 (4.9%) | 3/74 (4.1%) | |||
| Metabolism and nutrition disorders | ||||||
| Severe hypoglycemia | 1/133 (0.8%) | 1/144 (0.7%) | 0/74 (0%) | |||
| Renal and urinary disorders | ||||||
| Acute Renal Failure | 8/133 (6%) | 9/144 (6.3%) | 3/74 (4.1%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| pneumonia | 0/133 (0%) | 3/144 (2.1%) | 0/74 (0%) | |||
| Acute Respiratory Failure | 2/133 (1.5%) | 1/144 (0.7%) | 0/74 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Basal Plus Regimen | Basal Bolus | Sliding Scale Regular Insulin (SSRI) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 16/133 (12%) | 13/144 (9%) | 3/74 (4.1%) | |||
| Metabolism and nutrition disorders | ||||||
| Hypoglycemia | 16/133 (12%) | 13/144 (9%) | 3/74 (4.1%) | |||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Guillermo Umpierrez |
|---|---|
| Organization | EUSOM |
| Phone | 4047781665 |
| geumpie@emory.edu |
- IRB00020328a