Type 2 Diabetes Mellitus
Conditions
Brief summary
This trial will attempt to develop the use of Continuous Glucose Monitoring (CGM) as a tool for the evaluation of both new and existing pharmacological treatments for type 2 diabetes, using the twice daily administered dipeptidyl peptidase-4 (DPP4) inhibitor, vildagliptin as a probe. The primary hypothesis is that two weeks of treatment with 50 mg of oral Vildagliptin, twice daily will lead to a statistically significant decrease in 24 hour weighted-mean glucose (WMG) relative to placebo.
Interventions
DRUGVildagliptin
DRUGPlacebo
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of type 2 diabetes mellitus on a clinical regimen that is metformin alone, up to a maximum of 3 gram per day, on a background of lifestyle measures, and has a Hemoglobin A1C at screening of \> 7%. * If on antihyperglycemic therapy with both metformin and sulfonylurea with a Screening Visit/Visit 1 Hemoglobin A1C of \>= 6.5% and =\< 7.5%, should then discontinue sulfonylurea usage and undergo washout of sulfonylurea.
Exclusion criteria
* History of either stroke, chronic seizures or major neurological disorder within the last 6 months. * Untreated hypertension with a blood pressure of \> 160/95 mmHg. * History of neoplastic disease within the past 5 years. * History of hypersensitivity to vildagliptin or other DPP4 inhibitors. * Had major surgery, or donated or lost 1 unit (500 mL) of blood, or participated in another investigational study within 4 weeks prior to screen. * Used any illicit drug or abusively used alcohol within the past 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24 Hour Weighted Mean Glucose (WMG) At 2 Weeks | At 2 weeks after Placebo treatment and again at 2 weeks after Vildagliptin treatment | The 24 hour WMG was measured after 2 weeks of placebo treatment, and again after 2 weeks of vildagliptin treatment. Glucose was measured over a 24 hour period by having participants wear two continuous glucose monitors (CGM), which produced an average glucose value approximately every 5 minutes. Using these values, the concentration of glucose was calculated from Area Under the Curve 0-24 hours (AUC 0-24hr), and was expressed as 24 hour WMG. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hemoglobin A1C (HbA1C) At 2 Weeks | At 2 weeks after Placebo treatment and again at 2 weeks after Vildagliptin treatment | Blood samples were taken after 2 weeks of placebo treatment, and again after 2 weeks of vildagliptin treatment to measure the percentage of glycated hemoglobin, HbA1C. Units are therefore presented as HbA1c (%). |
| HbA1C At 12 Weeks | At 2 weeks after Placebo treatment and again at 12 weeks after Vildagliptin treatment | Blood samples were taken after 2 weeks of placebo treatment, and again after 12 weeks of vildagliptin treatment to measure the percentage of glycated hemoglobin, HbA1C. Units are therefore presented as HbA1c (%). |
Participant flow
Pre-assignment details
After enrollment, participants previously treated with both metformin and sulfonylurea, discontinued sulfonylurea usage and underwent washout of sulfonylurea over a period of 8 weeks prior to treatment. Non-washout participants were enrolled on a clinical regimen of metformin alone.
Participants by arm
| Arm | Count |
|---|---|
| Placebo → Vildagliptin Participants received placebo tablets orally, twice a day for 3 weeks, and then over the next 12 weeks received vildagliptin 50 mg tablets orally, twice daily | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| 3 Weeks Placebo | Withdrawal by Subject | 1 |
| 8 Weeks Washout | Inclusion/exclusion criteria not met | 1 |
Baseline characteristics
| Characteristic | Placebo → Vildagliptin |
|---|---|
| Age, Continuous | 62 Years STANDARD_DEVIATION 5.6 |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 23 | 6 / 24 |
| serious Total, serious adverse events | 0 / 23 | 0 / 24 |
Outcome results
Primary
24 Hour Weighted Mean Glucose (WMG) At 2 Weeks
The 24 hour WMG was measured after 2 weeks of placebo treatment, and again after 2 weeks of vildagliptin treatment. Glucose was measured over a 24 hour period by having participants wear two continuous glucose monitors (CGM), which produced an average glucose value approximately every 5 minutes. Using these values, the concentration of glucose was calculated from Area Under the Curve 0-24 hours (AUC 0-24hr), and was expressed as 24 hour WMG.
Time frame: At 2 weeks after Placebo treatment and again at 2 weeks after Vildagliptin treatment
Population: Per-Protocol Population: all participants who complied with the assigned medication during each period of study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 24 Hour Weighted Mean Glucose (WMG) At 2 Weeks | 126.9 mg/dL | Geometric Coefficient of Variation 16 |
| Vildagliptin | 24 Hour Weighted Mean Glucose (WMG) At 2 Weeks | 114.2 mg/dL | Geometric Coefficient of Variation 17 |
90% CI: [0.85, 0.96]
Secondary
HbA1C At 12 Weeks
Blood samples were taken after 2 weeks of placebo treatment, and again after 12 weeks of vildagliptin treatment to measure the percentage of glycated hemoglobin, HbA1C. Units are therefore presented as HbA1c (%).
Time frame: At 2 weeks after Placebo treatment and again at 12 weeks after Vildagliptin treatment
Population: Per-Protocol Population: all participants who complied with the assigned medication during each period of study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | HbA1C At 12 Weeks | 7.12 HbA1c (%) | Standard Deviation 0.54 |
| Vildagliptin | HbA1C At 12 Weeks | 6.66 HbA1c (%) | Standard Deviation 0.74 |
90% CI: [-0.62, -0.3]
Secondary
Hemoglobin A1C (HbA1C) At 2 Weeks
Blood samples were taken after 2 weeks of placebo treatment, and again after 2 weeks of vildagliptin treatment to measure the percentage of glycated hemoglobin, HbA1C. Units are therefore presented as HbA1c (%).
Time frame: At 2 weeks after Placebo treatment and again at 2 weeks after Vildagliptin treatment
Population: Per-Protocol Population: all participants who complied with the assigned medication during each period of study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Hemoglobin A1C (HbA1C) At 2 Weeks | 7.12 HbA1c (%) | Standard Deviation 0.54 |
| Vildagliptin | Hemoglobin A1C (HbA1C) At 2 Weeks | 6.82 HbA1c (%) | Standard Deviation 0.55 |
90% CI: [-0.36, -0.23]