Older Adults, Pre-diabetes
Conditions
Brief summary
The goal of this study is to evaluate the hypothesis that the addition of liraglutide, a long-acting glucagon-like peptide 1 (GLP-1) analogue, to a calorie-restricted diet will lead to greater weight loss than will a calorie-restricted diet alone in subjects who are older (50 to 60 years of age), overweight/obese, and prediabetic. These individuals have been selected for study because they are at greatly increased risk to develop type 2 diabetes (2DM) and cardiovascular disease (CVD), and it is hypothesized that the addition of liraglutide to a calorie-restricted diet will significantly decrease risk of these adverse outcomes. There is considerable evidence that GLP-I compounds, including liraglutide, improve glycemic control in patients with manifest 2DM. However, there is relatively little information as to the potential utility of these compounds in nondiabetic individual at greatly increased risk of 2DM and CVD. This research proposal is aimed at providing some of this information by quantifying the effects of liraglutide, a long-acting GLP-1 analogue, on weight loss, insulin secretion, insulin action, and multiple CVD risk factors in a very high risk group-older, overweight/obese, prediabetic individuals. Furthermore, by using specific methods, not surrogate estimates, and avoiding the confounding effects of glucotoxicity, it will be possible to gain new insights into the effects of GLP-1 on insulin secretion and insulin action.
Interventions
DRUGliraglutide
Dosing begins at 0.6 mg subcutaneous injection and increases each week, to 1.2 mg and maximum dose of 1.8 mg.
DRUGPlacebo
Double blinded will receive study pen with same dosing instructions starting at 0.6 mg, and each week increase to 1.2 mg and finally 1.8 mg at week three.
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
IFG, or IGT BMI 27.0-37.0 kg/m2
Exclusion criteria
DM, CAD, severe anemia, kidney or liver disease, hx of pancreatitis, gallstones, ETOH abuse, personnel or family history of medullary thyroid carcinoma or MEN-2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Weight Reported at 14 Weeks | Baseline and 14 weeks | Change in weight with caloric restriction plus liraglutide vs. caloric restriction and placebo over 14 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glucose-stimulated Insulin Secretion in Insulin AUC, Pmol/1x 4H | Baseline, 14 weeks | Absolute change in glucose-stimulated insulin secretion (GS-IS) associated with caloric restriction plus liraglutide vs. caloric restriction and placebo at 14 weeks |
| Insulin Resistance in the Liraglutide vs.Placebo Group After Calorie Restriction | Baseline, 14 weeks | Mean (+/- SD) change in insulin resistance associated with caloric restriction plus liraglutide vs. caloric restriction and placebo. |
Participant flow
Pre-assignment details
1 person qualified and enrolled in study but dropped out before being randomized to either group. Therefore is not counted in placebo or liraglutide group.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Both groups receive dietary weight loss intervention In addition one group received liraglutide and one group received placebo
Placebo: Double blinded will receive study pen with same dosing instructions starting at 0.6 mg, and each week increase to 1.2 mg and finally 1.8 mg at week three. | 27 |
| Liraglutide Both groups receive dietary weight loss intervention In addition one group received liraglutide and one group received placebo
liraglutide: Dosing begins at 0.6 mg subcutaneous injection and increases each week, to 1.2 mg and maximum dose of 1.8 mg. | 24 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 8 |
| Overall Study | Withdrawal by Subject | 6 | 3 |
Baseline characteristics
| Characteristic | Placebo | Liraglutide | Total |
|---|---|---|---|
| Age, Continuous | 58 years STANDARD_DEVIATION 8 | 58 years STANDARD_DEVIATION 7 | 58 years STANDARD_DEVIATION 7.5 |
| BMI | 31.9 kg/m^2 STANDARD_DEVIATION 3.5 | 31.9 kg/m^2 STANDARD_DEVIATION 2.7 | 31.9 kg/m^2 STANDARD_DEVIATION 3.1 |
| Region of Enrollment United States | 27 participants | 24 participants | 51 participants |
| Sex: Female, Male Female | 17 Participants | 16 Participants | 33 Participants |
| Sex: Female, Male Male | 10 Participants | 8 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 35 | 6 / 33 |
| serious Total, serious adverse events | 8 / 35 | 0 / 33 |
Outcome results
Primary
Change in Weight Reported at 14 Weeks
Change in weight with caloric restriction plus liraglutide vs. caloric restriction and placebo over 14 weeks.
Time frame: Baseline and 14 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change in Weight Reported at 14 Weeks | -3.3 kg |
| Liraglutide | Change in Weight Reported at 14 Weeks | -6.8 kg |
p-value: <0.05t-test, 2 sided
Secondary
Glucose-stimulated Insulin Secretion in Insulin AUC, Pmol/1x 4H
Absolute change in glucose-stimulated insulin secretion (GS-IS) associated with caloric restriction plus liraglutide vs. caloric restriction and placebo at 14 weeks
Time frame: Baseline, 14 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Glucose-stimulated Insulin Secretion in Insulin AUC, Pmol/1x 4H | -7.3 pmol/l x4 h |
| Liraglutide | Glucose-stimulated Insulin Secretion in Insulin AUC, Pmol/1x 4H | 34 pmol/l x4 h |
Secondary
Insulin Resistance in the Liraglutide vs.Placebo Group After Calorie Restriction
Mean (+/- SD) change in insulin resistance associated with caloric restriction plus liraglutide vs. caloric restriction and placebo.
Time frame: Baseline, 14 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Insulin Resistance in the Liraglutide vs.Placebo Group After Calorie Restriction | 2.8 mg/dL | Standard Deviation 35.9 |
| Liraglutide | Insulin Resistance in the Liraglutide vs.Placebo Group After Calorie Restriction | -57.5 mg/dL | Standard Deviation 44.2 |