Type 2 Diabetes
Conditions
Keywords
Type 2 diabetes, Insulin Glargine, Endogenous Glucose Production
Brief summary
The study is to determine the dose response relationship of insulin glargine in type 2 diabetes over a 24-hour period and measuring the differences in glucose production among the differing doses of glargine. Hypothesis: Differing doses of insulin glargine over a 24-hour period in type 2 diabetes will show differing effects on endogenous glucose production, glucose disposal and carbohydrate and lipid flux.
Detailed description
The incidence of type 2 DM is increasing worldwide at an alarming rate. Unfortunately, the number of individuals with glycemic control at or below the American Diabetes Association goal of 7% has dropped. In fact, the number of patients with their important cardiometabolic risk factors of glucose, lipids and blood pressure at goal is only 7%. One of the reasons for this lack of metabolic control in type 2 DM is the continued relative underutilization of insulin. Diabetes is an insulin deficient state and requires appropriate physiologic replacement of insulin. Physiologic replacement of insulin requires a basal component to restrain overnight endogenous glucose production, lipolysis and proteolysis. The other component involves prandial insulin to regulate post prandial glucose levels. Recently, insulin glargine was introduced as a once-a-day peakless basal insulin. This form of basal insulin reproduces the normal constitutive physiologic release of insulin from the pancreas. Insulin glargine represents a breakthrough in treatment as the previous available basal insulins either produced peaks of activity (which are disadvantageous as this results in hypoglycemia) or do not last 24 hrs which results in post absorbative hyperglycemia. Despite the undoubted advantages of insulin glargine, there remains a lack of information regarding some aspects of glargine action. The study objectives are: 1) to determine the pharmacokinetic and pharmacodynamic dose response relationship of insulin glargine in Type 2 DM; 2) partition the dose response relationship of insulin glargine on endogenous glucose production and glucose uptake in Type 2 DM; and 3) to determine if the pharmacokinetic and pharmacodynamics of insulin glargine are consistent over a wide range of doses.
Interventions
DRUGPlacebo
single dose of Placebo injected s/c at 8am and monitor blood glucose over 24 hours
DRUGInsulin Glargine 0.5 u/kg body wt SC
8 weeks later, a differing dose (0.5, 1.0, 1.5, 2.0 u/kg body wt.) of Insulin Glargine and monitoring over a 24 hour period each separated by 8 weeks (5 separate study visits)
DRUGInsulin Glargine 1.0 u/kg body wt SC
DRUGInsulin Glargine 1.5 u/kg body wt SC
DRUGInsulin Glargine 2.0 u/kg body wt SC
Sponsors
Sanofi
Vanderbilt University Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 12 adults (males or females) with type 2 diabetes for at least six (6) months. May be using oral agents (SUs, metformin, acarbose or glitinides) with or without insulin. * HgbA1c 7 -12% * Age 18-70 years * BMI 27-40 kg/m²
Exclusion criteria
* Any past or present clinically relevant abnormality, medical condition, or circumstance making the subject unsuitable for participation in the study * Evidence of hepatic, renal or cardiac failure * Abnormal results following screening tests * Pregnant or lactating females or females of childbearing potential who are unwilling to abstain from sexual intercourse or use reliable, medically accepted methods of contraception * Currently using TZDs * History of alcoholism or drug abuse within 12 months of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Glucose Infusion Rate | 24 hours | measuring the changes in glucose infusion rate during the 24 hour experimental period. |
Countries
United States
Participant flow
Recruitment details
12 individuals will be their own controls completing 5 separate 24 hour protocol studies. If a participant does not complete all protocols, another person will be recruited to complete the protocols until there are 12 completed studies in each arm/group.
Participants by arm
| Arm | Count |
|---|---|
| 1--All Interventions Arm: Other: 1--All interventions
All participant will be given all 5 interventions in the same order
Placebo, then 0.5 units of Glargine/kg body weight, then 1.0 units of Glargine/kg body weight, then 1.5 units of Glargine/kg body weight, then 2.0 units of Glargine/kg body weight, | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Could not place IV lines. | 3 |
| Overall Study | Physician Decision | 2 |
| Overall Study | scheduling conflicts | 3 |
Baseline characteristics
| Characteristic | 1--All Interventions |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Maximum Glucose Infusion Rate
measuring the changes in glucose infusion rate during the 24 hour experimental period.
Time frame: 24 hours
Population: 12 participants in each arm
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Glucose Infusion Rate | 0.3 umol/kg/min | Standard Error 0.3 |
| 0.5 Units of Glargine/kg | Maximum Glucose Infusion Rate | 2.6 umol/kg/min | Standard Error 0.9 |
| 1.0 Units of Glargine/kg | Maximum Glucose Infusion Rate | 5.5 umol/kg/min | Standard Error 1.5 |
| 1.5 Units of Glargine/kg | Maximum Glucose Infusion Rate | 6.8 umol/kg/min | Standard Error 2 |
| 2.0 Units of Glargine/kg | Maximum Glucose Infusion Rate | 9.5 umol/kg/min | Standard Error 2.1 |
p-value: <0.05ANOVA