Type 2 Diabetes Mellitus
Conditions
Keywords
Januvia, Sitagliptin, Diabetes, Gastric-Bypass
Brief summary
The purpose of this study is to assess whether Januvia (sitagliptin phosphate 100mg) is safe and effective for the treatment of Type 2 Diabetes in patients who have had Gastric Bypass.
Detailed description
Januvia (sitagliptin phosphate 100mg) is an FDA approved medication for the treatment of Type 2 Diabetes. Sitagliptin works by inhibiting the Dipeptidyl peptidase-4 enzyme, resulting in increased active glucagon-like peptide-1 (GLP-1) levels. GLP-1 is an incretin which increases post-prandial insulin secretion. Because Gastric Bypass has also been shown to increase GLP-1 levels, this study seeks to determine the additional effect of DDP-4 inhibition on glucose control in patients who have elevated incretin levels post Gastric Bypass. The study will also assess if Januvia (Sitagliptin phosphate) is safe and well tolerated in patients after Gastric Bypass. Recruitment and data collection for this study was started at St. Luke's Hospital in New York, NY and later moved to Columbia University Medical Center in New York, NY.
Interventions
DRUGSitagliptin phosphate
100 mg/day orally
OTHERPlacebo
1 Placebo Pill per day
Sponsors
Merck Sharp & Dohme LLC
Blandine Laferrere
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Must be a resident of the NYC metropolitan area or be able to come for emergency unscheduled and regular weekly meetings in Manhattan. * HbA1c ≥ 6.5% and ≤ 8.5 % or a fasting glucose ≥ 126 mg/dL or a random glucose ≥ 200 mg/dL at least 12 months after GBP surgery confirmed by central laboratory. * Subject is capable and willing to give informed consent. * Subject is otherwise in good general health, based on medical history and physical examination. * Subject is a non smoker for at least 6 months prior to study start * Female subjects of child bearing potential must use oral, injected or implanted hormonal methods of contraception from at least the commencement of their last normal period prior to the first administration of the challenge agent. Subjects using hormonal contraception should use a barrier method in addition from the first administration of challenge agent until their next normal period following the end of the study.
Exclusion criteria
* History of type 1 diabetes * Female subject is pregnant or breastfeeding. * Recent (\< 30 days) or simultaneous participation in another clinical trial. * Any situation that can compromise the study, including serious illness or a predictable lack of cooperation from the subject.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Postprandial Glucose Levels After Mixed Meal Test | Baseline and ~4 weeks | Glucose levels were measured in study participants while fasting and periodically over 3 hours after drinking a 200 kcal mixed meal test, before and after intervention (Sitagliptin or Placebo). |
| Change in Area Under the Curve (AUC) Glucose Levels After Mixed Meal Test | Baseline and ~4 weeks | Glucose levels were measured in study participants while fasting and periodically over 3 hours after drinking a 200 kcal mixed meal test, before and after intervention (Sitagliptin or Placebo). AUC was measured by trapezoidal method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Sitagliptin vs Placebo on Satiety in Patients With Type 2 Diabetes After Gastric Bypass Surgery | Baseline and ~4 weeks | Satiety levels were measured in study participants while they were fasting and periodically over a three hour period after drinking a 200 kcal meal drink, before and after intervention via a Visual Analog Scale. Participants were asked to mark on a 0 to 150 millimeter scale their response to the following question: How full do you feel right now? with lower scores indicating not full at all and higher scores indicating extremely full. |
| Occurrence of Side Effects In Relation to Sitagliptin | 6 weeks | Side effects to Sitagliptin or Placebo were measured in study participants via Sigstad score questionnaire, while fasting and periodically during a 3 hour period after drinking a 200 kcal meal drink, before and after intervention. The Sigstad scoring system is based on the participants report of the occurrence of 16 symptoms suggestive of the dumping syndrome. Each symptom is given a different score. For example, desire to sit down (+4), breathlessness (+3), dizziness (+2), nausea (+1), vomiting (-4) etc.The scale can range from -5 to 34. Scores greater than or equal to 7, after glucose intake, are considered diagnostic of dumping syndrome. |
| Active GLP-1 | Pre-Intervention and Post-Intervention | Active GLP-1 (Fasting and during a Mixed Meal Test). The Change in Fasting Active GLP-1 refers to the change in fasting active GLP-1 from pre-intervention time point to post-intervention time point. The Change in Peak Active GLP-1 refers to the change in the peak active GLP-1 level from the pre-intervention time point to post-intervention time point. |
Countries
United States
Participant flow
Recruitment details
Recruitment for this study took place from July 2012-July 2016. Recruitment and data collection for this study was started at St. Luke's Hospital in New York, NY and later moved to Columbia University Medical Center in New York, NY.
Pre-assignment details
37 participants were enrolled, however only 32 participated in study procedures and demographic information collection.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin Phosphate 100 mg/day sitagliptin phosphate (Januvia) PO once a day for 4-5 weeks
Sitagliptin phosphate: 100 mg/day orally | 16 |
| Placebo 1 Placebo pill / day PO once a day for 4-5 weeks
Placebo: 1 Placebo Pill per day | 16 |
| Total | 32 |
Baseline characteristics
| Characteristic | Sitagliptin Phosphate | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 54.2 years STANDARD_DEVIATION 9 | 56.3 years STANDARD_DEVIATION 8.2 | 58.4 years STANDARD_DEVIATION 7 |
| BMI | 32.70 kg/m2 STANDARD_DEVIATION 5.22 | 34.41 kg/m2 STANDARD_DEVIATION 6.69 | 36.12 kg/m2 STANDARD_DEVIATION 7.69 |
| Current Weight | 85.98 kg STANDARD_DEVIATION 15.21 | 90.90 kg STANDARD_DEVIATION 18.02 | 95.82 kg STANDARD_DEVIATION 19.71 |
| Current weight loss since Roux-en-Y gastric bypass | 31.53 kg STANDARD_DEVIATION 11.9 | 33.00 kg STANDARD_DEVIATION 12.82 | 34.47 kg STANDARD_DEVIATION 13.91 |
| Diastolic blood pressure | 74.69 mm Hg STANDARD_DEVIATION 12.26 | 72.48 mm Hg STANDARD_DEVIATION 11.79 | 69.77 mm Hg STANDARD_DEVIATION 11.05 |
| HbA1c | 7.46 % STANDARD_DEVIATION 0.78 | 7.21 % STANDARD_DEVIATION 0.77 | 6.96 % STANDARD_DEVIATION 0.7 |
| High-density lipoprotein | 54.83 mg/dL STANDARD_DEVIATION 15.21 | 57.19 mg/dL STANDARD_DEVIATION 23.58 | 59.21 mg/dL STANDARD_DEVIATION 29.39 |
| Low-density lipoprotein | 89.18 mg/dL STANDARD_DEVIATION 39.92 | 82.24 mg/dL STANDARD_DEVIATION 33.7 | 76.79 mg/dL STANDARD_DEVIATION 28.24 |
| Maximum Weight before Roux-en-Y gastric bypass surgery | 122.45 kg STANDARD_DEVIATION 19 | 127.7 kg STANDARD_DEVIATION 22.1 | 132.89 kg STANDARD_DEVIATION 24.23 |
| Nadir weight after Roux-en-Y gastric bypass | 73.51 kg STANDARD_DEVIATION 17.52 | 78.22 kg STANDARD_DEVIATION 16.06 | 82.93 kg STANDARD_DEVIATION 13.38 |
| Number of oral type 2 diabetes mellitus medications prior to Roux-en-Y gastric bypass | 1.88 number of medications STANDARD_DEVIATION 0.89 | 1.81 number of medications STANDARD_DEVIATION 0.9 | 1.75 number of medications STANDARD_DEVIATION 0.93 |
| Participants on insulin at time of study | 3 Participants | 7 Participants | 4 Participants |
| Participants on insulin prior to RYGB | 10 Participants | 20 Participants | 10 Participants |
| Race/Ethnicity, Customized African-American | 5 Participants | 9 Participants | 4 Participants |
| Race/Ethnicity, Customized Caucasian | 4 Participants | 8 Participants | 4 Participants |
| Race/Ethnicity, Customized Hispanic Black | 2 Participants | 5 Participants | 3 Participants |
| Race/Ethnicity, Customized Hispanic White | 5 Participants | 10 Participants | 5 Participants |
| Sex: Female, Male Female | 15 Participants | 29 Participants | 14 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 2 Participants |
| Systolic blood pressure | 124.8 mm Hg STANDARD_DEVIATION 21.23 | 122.23 mm Hg STANDARD_DEVIATION 18.4 | 119.1 mm Hg STANDARD_DEVIATION 14.4 |
| Time since Roux-en-Y gastric bypass surgery | 5.56 years STANDARD_DEVIATION 3.77 | 5.56 years STANDARD_DEVIATION 3.27 | 5.57 years STANDARD_DEVIATION 2.8 |
| Total Cholesterol | 172.0 mg/dL STANDARD_DEVIATION 41.5 | 161.1 mg/dL STANDARD_DEVIATION 37.67 | 151.78 mg/dL STANDARD_DEVIATION 32.67 |
| Triglycerides | 147.3 mg/dL STANDARD_DEVIATION 123.9 | 135.1 mg/dL STANDARD_DEVIATION 90.6 | 124.7 mg/dL STANDARD_DEVIATION 50.2 |
| Type 2 Diabetes Mellitus duration prior to Roux-en-Y gastric bypass surgery | 12.9 years STANDARD_DEVIATION 11 | 12.9 years STANDARD_DEVIATION 10 | 12.9 years STANDARD_DEVIATION 9.3 |
| Type 2 Diabetes Mellitus remission duration prior to study | 2.72 years STANDARD_DEVIATION 3.1 | 2.44 years STANDARD_DEVIATION 2.89 | 2.16 years STANDARD_DEVIATION 2.74 |
| Weight at Roux-en-Y gastric bypass | 117.5 kg STANDARD_DEVIATION 20.4 | 123.9 kg STANDARD_DEVIATION 23.1 | 130.23 kg STANDARD_DEVIATION 24.6 |
| Weight regain from nadir weight | 12.73 kg STANDARD_DEVIATION 10.7 | 12.84 kg STANDARD_DEVIATION 10.64 | 12.96 kg STANDARD_DEVIATION 10.94 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 0 / 16 | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
Change in Area Under the Curve (AUC) Glucose Levels After Mixed Meal Test
Glucose levels were measured in study participants while fasting and periodically over 3 hours after drinking a 200 kcal mixed meal test, before and after intervention (Sitagliptin or Placebo). AUC was measured by trapezoidal method.
Time frame: Baseline and ~4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitagliptin Phosphate | Change in Area Under the Curve (AUC) Glucose Levels After Mixed Meal Test | Pre-Intervention Glucose AUC | 8.31 mmol/L/min | Standard Deviation 1.92 |
| Sitagliptin Phosphate | Change in Area Under the Curve (AUC) Glucose Levels After Mixed Meal Test | Post-Intervention Glucose AUC | 7.67 mmol/L/min | Standard Deviation 1.59 |
| Placebo | Change in Area Under the Curve (AUC) Glucose Levels After Mixed Meal Test | Pre-Intervention Glucose AUC | 7.96 mmol/L/min | Standard Deviation 1.2 |
| Placebo | Change in Area Under the Curve (AUC) Glucose Levels After Mixed Meal Test | Post-Intervention Glucose AUC | 7.75 mmol/L/min | Standard Deviation 1.16 |
Primary
Change in Postprandial Glucose Levels After Mixed Meal Test
Glucose levels were measured in study participants while fasting and periodically over 3 hours after drinking a 200 kcal mixed meal test, before and after intervention (Sitagliptin or Placebo).
Time frame: Baseline and ~4 weeks
Population: All patients completed study in both arms.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitagliptin Phosphate | Change in Postprandial Glucose Levels After Mixed Meal Test | Pre-Intervention Fasting Glucose | 7.10 mmol/L | Standard Deviation 1.74 |
| Sitagliptin Phosphate | Change in Postprandial Glucose Levels After Mixed Meal Test | Post-Intervention Fasting Glucose | 6.44 mmol/L | Standard Deviation 1.25 |
| Sitagliptin Phosphate | Change in Postprandial Glucose Levels After Mixed Meal Test | Pre-Intervention 120 minute glucose | 7.51 mmol/L | Standard Deviation 1.91 |
| Sitagliptin Phosphate | Change in Postprandial Glucose Levels After Mixed Meal Test | Post-Intervention 120 minute glucose | 6.79 mmol/L | Standard Deviation 1.65 |
| Sitagliptin Phosphate | Change in Postprandial Glucose Levels After Mixed Meal Test | Pre-Intervention Average Glucose during MMT | 8.55 mmol/L | Standard Deviation 1.95 |
| Sitagliptin Phosphate | Change in Postprandial Glucose Levels After Mixed Meal Test | Post-Intervention Average Glucose during MMT | 7.84 mmol/L | Standard Deviation 1.47 |
| Placebo | Change in Postprandial Glucose Levels After Mixed Meal Test | Pre-Intervention Average Glucose during MMT | 8.12 mmol/L | Standard Deviation 1.14 |
| Placebo | Change in Postprandial Glucose Levels After Mixed Meal Test | Pre-Intervention Fasting Glucose | 6.52 mmol/L | Standard Deviation 1.21 |
| Placebo | Change in Postprandial Glucose Levels After Mixed Meal Test | Post-Intervention 120 minute glucose | 6.97 mmol/L | Standard Deviation 1.47 |
| Placebo | Change in Postprandial Glucose Levels After Mixed Meal Test | Post-Intervention Fasting Glucose | 6.39 mmol/L | Standard Deviation 1.23 |
| Placebo | Change in Postprandial Glucose Levels After Mixed Meal Test | Post-Intervention Average Glucose during MMT | 7.86 mmol/L | Standard Deviation 1.04 |
| Placebo | Change in Postprandial Glucose Levels After Mixed Meal Test | Pre-Intervention 120 minute glucose | 7.01 mmol/L | Standard Deviation 1.38 |
Comparison: Power analysis. Based on the effect of DPP-4 inhibitors in non-operated subjects with type 2 diabetes, showing a significant decrease in 120' post-prandial glucose by 1.67 mmol/L ± 0.98 mmol/L after a MMT, we estimated that a sample size of 16 subjects per group will show post-prandial glucose differences between placebo and sitagliptin group with α = 0.05 for a power \> 90%.p-value: 0.028t-test, 2 sided
Secondary
Active GLP-1
Active GLP-1 (Fasting and during a Mixed Meal Test). The Change in Fasting Active GLP-1 refers to the change in fasting active GLP-1 from pre-intervention time point to post-intervention time point. The Change in Peak Active GLP-1 refers to the change in the peak active GLP-1 level from the pre-intervention time point to post-intervention time point.
Time frame: Pre-Intervention and Post-Intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitagliptin Phosphate | Active GLP-1 | Change in Fasting Active GLP-1 | 1.45 pmol/L | Standard Deviation 2.59 |
| Sitagliptin Phosphate | Active GLP-1 | Change in Peak Active GLP-1 | 22.08 pmol/L | Standard Deviation 15.46 |
| Placebo | Active GLP-1 | Change in Fasting Active GLP-1 | -0.22 pmol/L | Standard Deviation 0.88 |
| Placebo | Active GLP-1 | Change in Peak Active GLP-1 | 2.97 pmol/L | Standard Deviation 10.44 |
Secondary
Effect of Sitagliptin vs Placebo on Satiety in Patients With Type 2 Diabetes After Gastric Bypass Surgery
Satiety levels were measured in study participants while they were fasting and periodically over a three hour period after drinking a 200 kcal meal drink, before and after intervention via a Visual Analog Scale. Participants were asked to mark on a 0 to 150 millimeter scale their response to the following question: How full do you feel right now? with lower scores indicating not full at all and higher scores indicating extremely full.
Time frame: Baseline and ~4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitagliptin Phosphate | Effect of Sitagliptin vs Placebo on Satiety in Patients With Type 2 Diabetes After Gastric Bypass Surgery | Pre-Intervention fasting satiety level | 51.94 mm | Standard Deviation 87.4 |
| Sitagliptin Phosphate | Effect of Sitagliptin vs Placebo on Satiety in Patients With Type 2 Diabetes After Gastric Bypass Surgery | Post-Intervention fasting satiety level | 22.38 mm | Standard Deviation 22.03 |
| Sitagliptin Phosphate | Effect of Sitagliptin vs Placebo on Satiety in Patients With Type 2 Diabetes After Gastric Bypass Surgery | Pre-Intervention 180 minute glucose | 37.81 mm | Standard Deviation 40.95 |
| Sitagliptin Phosphate | Effect of Sitagliptin vs Placebo on Satiety in Patients With Type 2 Diabetes After Gastric Bypass Surgery | Post-Intervention 180 minute glucose | 43.69 mm | Standard Deviation 43.85 |
| Placebo | Effect of Sitagliptin vs Placebo on Satiety in Patients With Type 2 Diabetes After Gastric Bypass Surgery | Post-Intervention 180 minute glucose | 103.75 mm | Standard Deviation 198.35 |
| Placebo | Effect of Sitagliptin vs Placebo on Satiety in Patients With Type 2 Diabetes After Gastric Bypass Surgery | Pre-Intervention fasting satiety level | 49.06 mm | Standard Deviation 39.36 |
| Placebo | Effect of Sitagliptin vs Placebo on Satiety in Patients With Type 2 Diabetes After Gastric Bypass Surgery | Pre-Intervention 180 minute glucose | 50.50 mm | Standard Deviation 59.37 |
| Placebo | Effect of Sitagliptin vs Placebo on Satiety in Patients With Type 2 Diabetes After Gastric Bypass Surgery | Post-Intervention fasting satiety level | 58.50 mm | Standard Deviation 113.23 |
Secondary
Occurrence of Side Effects In Relation to Sitagliptin
Side effects to Sitagliptin or Placebo were measured in study participants via Sigstad score questionnaire, while fasting and periodically during a 3 hour period after drinking a 200 kcal meal drink, before and after intervention. The Sigstad scoring system is based on the participants report of the occurrence of 16 symptoms suggestive of the dumping syndrome. Each symptom is given a different score. For example, desire to sit down (+4), breathlessness (+3), dizziness (+2), nausea (+1), vomiting (-4) etc.The scale can range from -5 to 34. Scores greater than or equal to 7, after glucose intake, are considered diagnostic of dumping syndrome.
Time frame: 6 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitagliptin Phosphate | Occurrence of Side Effects In Relation to Sitagliptin | Pre-Intervention Average Sigstad Score | 2.15 units on Sigstad scale | Standard Deviation 1.97 |
| Sitagliptin Phosphate | Occurrence of Side Effects In Relation to Sitagliptin | Post-Intervention Average Sigstad Score | 2.24 units on Sigstad scale | Standard Deviation 2.34 |
| Placebo | Occurrence of Side Effects In Relation to Sitagliptin | Pre-Intervention Average Sigstad Score | 5.58 units on Sigstad scale | Standard Deviation 3.41 |
| Placebo | Occurrence of Side Effects In Relation to Sitagliptin | Post-Intervention Average Sigstad Score | 4.40 units on Sigstad scale | Standard Deviation 3.1 |