Type 2 Diabetes Mellitus, Hospitalization, Hyperglycemia
Conditions
Keywords
diabetes, non critical care setting, hyperglycemia, treatment, oral antidiabetic agents, subcutaneous insulin
Brief summary
The study is a multicenter, prospective, open-label, randomized pilot study to investigate the safety and efficacy of sitagliptin (Januvia) for the inpatient management of type 2 diabetes (T2D) in general medicine and surgery patients.
Detailed description
High blood glucose levels in hospitalized patients with diabetes are associated with increased risk of medical complications and death. Improved glucose control with insulin injections may improve clinical outcome and prevent some of the hospital complications. Glargine (Lantus®) insulin injection is the most common treatment of diabetes in the hospital. Sitagliptin (Januvia®)is effective in lowering blood glucose, but has not been tested in the hospital. It is not known if sitagliptin is as effective in controlling blood sugars in the hospital. This study will compare sitagliptin by mouth, insulin (glargine) injection, and the combination of sitagliptin and lantus insulin in controlling blood sugar in hospitalized patients with diabetes. In this pilot study, patients with known history of diabetes treated with diet and/or oral anti-diabetics or with low total daily dose insulin therapy (\<0.4 unit/kg/day) will be randomized to receive sitagliptin once daily (group 1), sitagliptin plus basal (glargine) insulin once daily (group 2), or basal bolus regimen with glargine once daily and lispro insulin before meals (group 3). If needed, patients in the 3 treatment groups will receive correction doses of rapid-acting lispro (Humalog®) insulin in the presence of hyperglycemia (BG \> 140 mg/dl) per sliding scale. The overall hypothesis is that treatment with sitagliptin once daily alone or in combination with basal insulin in patients with type 2 diabetes will result in a similar improvement in glycemic control and in a lower frequency of hypoglycemic events than treatment with basal bolus insulin regimen with glargine once daily and lispro insulin before meals. A total of 90 subjects with type 2 diabetes will be recruited in this study. Patients will be recruited at Grady Memorial Hospital and Emory University Hospital.
Interventions
DRUGSitagliptin
Sitagliptin 50-100mg po once daily
DRUGglargine
glargine once daily
DRUGlispro
lispro before meals
Sponsors
Merck Sharp & Dohme LLC
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Males or females between the ages of 18 and 80 years admitted to a general medicine and surgery services. 2. A known history of type 2 diabetes mellitus \> 3 months, receiving either diet alone, oral antidiabetic agents: sulfonylureas and metformin as monotherapy or in combination therapy (excluding Trazodone (TZDs) and DPP4 inhibitors), or low-dose (≤ 0.4 units/kg/day) insulin therapy. 3. Subjects with a BG \>140 mg and \< 400 mg/dL without laboratory evidence of diabetic ketoacidosis (serum bicarbonate \< 18 milliequivalent /L or positive serum or urinary ketones).
Exclusion criteria
1. Age \< 18 or \> 80 years. 2. Subjects with increased blood glucose concentration, but without a known history of diabetes (stress hyperglycemia). 3. Subjects with a history of type 1 diabetes (suggested by BMI \< 25 requiring insulin therapy or with a history of diabetic ketoacidosis and hyperosmolar hyperglycemic state, or ketonuria) \[46\]. 4. History of TZD treatment (pioglitazone or rosiglitazone) or DPP4 inhibitor (sitagliptin or saxagliptin) during the past 3 months prior to admission. 5. Acute critical illness or coronary artery bypass graft (CABG) surgery expected to require prolonged admission to a critical care unit (ICU, cardiac care unit , surgical intensive care unit, neuro ICU). 6. Subjects with gastrointestinal obstruction or adynamic ileus or those expected to require gastrointestinal suction. 7. Medical or surgical patients expected to be kept nil per os (NPO) for \>24-48 hours after admission or after completion of surgical procedure. 8. Patients with clinically relevant pancreatic or gallbladder disease. 9. Patients with congestive heart failure (NYHA class III and IV), acute myocardial infarction, clinically significant hepatic disease or significantly impaired renal function (serum creatinine ≥ 2.0 mg/dL). 10. Treatment with oral or injectable corticosteroid. 11. Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study. 12. Female subjects are pregnant or breast feeding at time of enrollment into the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Blood Glucose Levels Among the Three Groups at the Time of Hospitalization to 1st Day After Therapy | Admission and after 1st day of therapy | The primary outcome of the study is to determine differences in glycemic control as measured by mean BG concentration between sitagliptin once daily and basal bolus therapy with glargine once daily plus supplemental lispro insulin in hospitalized patients with type 2 diabetes mellitus, at the time of admission to the blood glucose levels 24hrs after the therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Severe Hypoglycemic Episodes Among the 3 Treatment Groups | during hospitalization,up to 5 days | severe hypoglycemic episodes are defined as blood glucose levels \<40 mg/dl. The number of patients with these events during the 5 days of hospitalization are recorded and compared. BG was measured before each meal and at bedtime (or every 6 h if a patient was not eating) using a point-of-care glucose meter. |
| Number of Patients With a Mean Daily BG > 240 mg/dL After the 1st Day of Treatment Among the Treatment Groups | during hospitalization,up to 10 days | Mean daily blood glucose levels are measured to assess the treatment Failures. For study purpose Treatment failure was defined as having three or more consecutive Blood Glucose (BG) readings \> 240 mg/dL or a mean daily BG \>240 mg/dL after the 1st day of treatment. Number of patients with a mean daily BG \> 240 mg/dL after the 1st day of treatment are recorded and compared among the treatment groups. BG was measured before each meal and at bedtime (or every 6 h if a patient was not eating) using a point-of-care glucose meter. |
| Mean Total Daily Dose of Insulin in Units/Day Given During Hospitalization Among the Three Groups | during hospitalization, up to 10 days | The total insulin includes total glargine insulin (units/day) and total lispro insulin (units/day) given to subjects for maintaining blood glucose levels during hospitalization in different groups. The goal of therapy was to maintain a fasting and premeal glucose concentration between 100 and 140 mg/dL. The doses of insulin were adjusted daily according to protocol. The mean amount is calculated among the different groups and compared. |
| Number of Patients With Hypoglycemic Events Among the Treatment Groups | during hospitalization,up to 10 days | Hypoglycemia is defined as blood glucose (BG) reading \<70 mg/dl. The number of hypoglycemia events during hospitalization are recorded and compared among the different groups. BG was measured before each meal and at bedtime (or every 6 h if a patient was not eating) using a point-of-care glucose meter |
| Number of Subjects With Acute Renal Failure Among the Three Randomized Groups During Hospitalization | during hospitalization, up to 10 days | Acute renal failure is defined as a clinical diagnosis of acute renal failure with documented new-onset abnormal renal function (serum creatinine \> 2.2 mg/dL or an increment \> 0.5 mg/dL from baseline). The total daily dose of insulin and sitagliptin will be adjusted as per serum creatinine concentration. The total daily insulin dose will be reduced to 0.3 unit/kg in patients with creatinine \>1.7 mg/dl. The dose of sitagliptin will be reduced to 50 mg/day in patients with creatinine clearance between 30-50 ml/min (approximate serum creatinine levels \>1.7 and ≤3.0 mg/dl for men and \>1.5 and ≤2.5 mg/dl for women). |
| Number of Deaths Among the Subjects in Different Groups | during hospitalization, up to 10 days | Mortality is defined as death occurring during admission among the participants. The number of deaths in each assigned group is calculated. |
| Percent of Blood Glucose Readings Within Target Range Between 70 and 140 mg/dL Among the Three Groups After 24 Hrs of Randomized Treatment | during hospitalization, up to 10 days | The blood glucose within target range is defined as the levels between 70 mg/dL and 140 mg/dL. BG was measured before each meal and at bedtime (or every 6 h if a patient was not eating) using a point-of-care glucose meter (ACCUCHECK; Roche, Indianapolis, IN). In addition, BG was measured at any time if a patient experienced symptoms of hypoglycemia or if requested by the treating physician. the percentage of the readings are calculated and compared |
| Mean Length of Stay in Days in the Hospital Among Different Groups | during hospitalization, up to 10 days | The duration of stay in days in the hospital between the three groups is calculated and mean number of days is measured. |
Countries
United States
Participant flow
Recruitment details
90 patients admitted to general medicine and surgery services in 2012 were enrolled in this pilot study. This study was conducted at Grady Memorial Hospital (Atlanta, GA), Emory University Hospital, and University of Michigan Health System.
Pre-assignment details
Patients were included if they had Type 2 Diabetes with a BG 140-400 mg/dL and were treated at home with diet, oral antidiabetics, or low-dose insulin. 8 patients were excluded from further analysis because they received \<24 h of insulin treatment, were transferred to the ICU, or received corticosteroid therapy.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin + SSI Prn Sitagliptin once daily plus supplemental doses of lispro if needed. | 27 |
| Sitagliptin and Glargine + SSI Sitagliptin 50-100 mg po once a day and subcutaneous glargine insulin once daily + correctional doses of lispro if needed for elevated blood glucose using sliding scale Insulin (SSI) | 29 |
| Glargine and Lispro + SSI Glargine once daily and lispro before meals + supplemental insulin lispro as needed for elevated blood glucose using sliding scale Insulin (SSI) | 26 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | discharged before med given | 2 | 0 | 1 |
| Overall Study | withdrawal | 2 | 1 | 2 |
Baseline characteristics
| Characteristic | Sitagliptin and Glargine + SSI | Glargine and Lispro + SSI | Sitagliptin + SSI Prn | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 4 Participants | 5 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 22 Participants | 22 Participants | 67 Participants |
| Age, Continuous | 58 years STANDARD_DEVIATION 12 | 57 years STANDARD_DEVIATION 10 | 59 years STANDARD_DEVIATION 11 | 58 years STANDARD_DEVIATION 11 |
| Region of Enrollment United States | 29 participants | 26 participants | 27 participants | 82 participants |
| Sex: Female, Male Female | 16 Participants | 8 Participants | 10 Participants | 34 Participants |
| Sex: Female, Male Male | 13 Participants | 18 Participants | 17 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 29 | 0 / 26 |
| other Total, other adverse events | 8 / 27 | 7 / 29 | 8 / 26 |
| serious Total, serious adverse events | 1 / 27 | 0 / 29 | 0 / 26 |
Outcome results
Primary
Mean Blood Glucose Levels Among the Three Groups at the Time of Hospitalization to 1st Day After Therapy
The primary outcome of the study is to determine differences in glycemic control as measured by mean BG concentration between sitagliptin once daily and basal bolus therapy with glargine once daily plus supplemental lispro insulin in hospitalized patients with type 2 diabetes mellitus, at the time of admission to the blood glucose levels 24hrs after the therapy
Time frame: Admission and after 1st day of therapy
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitagliptin + SSI Prn | Mean Blood Glucose Levels Among the Three Groups at the Time of Hospitalization to 1st Day After Therapy | At time of admission | 209 mg/dl | Standard Deviation 67 |
| Sitagliptin + SSI Prn | Mean Blood Glucose Levels Among the Three Groups at the Time of Hospitalization to 1st Day After Therapy | After 1st day of therapy | 168.4 mg/dl | Standard Deviation 35 |
| Sitagliptin and Glargine + SSI | Mean Blood Glucose Levels Among the Three Groups at the Time of Hospitalization to 1st Day After Therapy | At time of admission | 203 mg/dl | Standard Deviation 48 |
| Sitagliptin and Glargine + SSI | Mean Blood Glucose Levels Among the Three Groups at the Time of Hospitalization to 1st Day After Therapy | After 1st day of therapy | 154.2 mg/dl | Standard Deviation 29 |
| Glargine and Lispro + SSI | Mean Blood Glucose Levels Among the Three Groups at the Time of Hospitalization to 1st Day After Therapy | At time of admission | 225 mg/dl | Standard Deviation 74 |
| Glargine and Lispro + SSI | Mean Blood Glucose Levels Among the Three Groups at the Time of Hospitalization to 1st Day After Therapy | After 1st day of therapy | 158.3 mg/dl | Standard Deviation 31 |
Secondary
Mean Length of Stay in Days in the Hospital Among Different Groups
The duration of stay in days in the hospital between the three groups is calculated and mean number of days is measured.
Time frame: during hospitalization, up to 10 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin + SSI Prn | Mean Length of Stay in Days in the Hospital Among Different Groups | 6.3 days | Standard Deviation 3 |
| Sitagliptin and Glargine + SSI | Mean Length of Stay in Days in the Hospital Among Different Groups | 6.9 days | Standard Deviation 3 |
| Glargine and Lispro + SSI | Mean Length of Stay in Days in the Hospital Among Different Groups | 6.3 days | Standard Deviation 3 |
Secondary
Mean Total Daily Dose of Insulin in Units/Day Given During Hospitalization Among the Three Groups
The total insulin includes total glargine insulin (units/day) and total lispro insulin (units/day) given to subjects for maintaining blood glucose levels during hospitalization in different groups. The goal of therapy was to maintain a fasting and premeal glucose concentration between 100 and 140 mg/dL. The doses of insulin were adjusted daily according to protocol. The mean amount is calculated among the different groups and compared.
Time frame: during hospitalization, up to 10 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin + SSI Prn | Mean Total Daily Dose of Insulin in Units/Day Given During Hospitalization Among the Three Groups | 11.5 units/day | Standard Deviation 7 |
| Sitagliptin and Glargine + SSI | Mean Total Daily Dose of Insulin in Units/Day Given During Hospitalization Among the Three Groups | 28.2 units/day | Standard Deviation 12 |
| Glargine and Lispro + SSI | Mean Total Daily Dose of Insulin in Units/Day Given During Hospitalization Among the Three Groups | 39.8 units/day | Standard Deviation 22 |
Secondary
Number of Deaths Among the Subjects in Different Groups
Mortality is defined as death occurring during admission among the participants. The number of deaths in each assigned group is calculated.
Time frame: during hospitalization, up to 10 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sitagliptin + SSI Prn | Number of Deaths Among the Subjects in Different Groups | 0 Participants |
| Sitagliptin and Glargine + SSI | Number of Deaths Among the Subjects in Different Groups | 0 Participants |
| Glargine and Lispro + SSI | Number of Deaths Among the Subjects in Different Groups | 0 Participants |
Secondary
Number of Patients With a Mean Daily BG > 240 mg/dL After the 1st Day of Treatment Among the Treatment Groups
Mean daily blood glucose levels are measured to assess the treatment Failures. For study purpose Treatment failure was defined as having three or more consecutive Blood Glucose (BG) readings \> 240 mg/dL or a mean daily BG \>240 mg/dL after the 1st day of treatment. Number of patients with a mean daily BG \> 240 mg/dL after the 1st day of treatment are recorded and compared among the treatment groups. BG was measured before each meal and at bedtime (or every 6 h if a patient was not eating) using a point-of-care glucose meter.
Time frame: during hospitalization,up to 10 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sitagliptin + SSI Prn | Number of Patients With a Mean Daily BG > 240 mg/dL After the 1st Day of Treatment Among the Treatment Groups | 3 Participants |
| Sitagliptin and Glargine + SSI | Number of Patients With a Mean Daily BG > 240 mg/dL After the 1st Day of Treatment Among the Treatment Groups | 1 Participants |
| Glargine and Lispro + SSI | Number of Patients With a Mean Daily BG > 240 mg/dL After the 1st Day of Treatment Among the Treatment Groups | 2 Participants |
Secondary
Number of Patients With Hypoglycemic Events Among the Treatment Groups
Hypoglycemia is defined as blood glucose (BG) reading \<70 mg/dl. The number of hypoglycemia events during hospitalization are recorded and compared among the different groups. BG was measured before each meal and at bedtime (or every 6 h if a patient was not eating) using a point-of-care glucose meter
Time frame: during hospitalization,up to 10 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sitagliptin + SSI Prn | Number of Patients With Hypoglycemic Events Among the Treatment Groups | 1 Participants |
| Sitagliptin and Glargine + SSI | Number of Patients With Hypoglycemic Events Among the Treatment Groups | 2 Participants |
| Glargine and Lispro + SSI | Number of Patients With Hypoglycemic Events Among the Treatment Groups | 2 Participants |
Secondary
Number of Patients With Severe Hypoglycemic Episodes Among the 3 Treatment Groups
severe hypoglycemic episodes are defined as blood glucose levels \<40 mg/dl. The number of patients with these events during the 5 days of hospitalization are recorded and compared. BG was measured before each meal and at bedtime (or every 6 h if a patient was not eating) using a point-of-care glucose meter.
Time frame: during hospitalization,up to 5 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sitagliptin + SSI Prn | Number of Patients With Severe Hypoglycemic Episodes Among the 3 Treatment Groups | 0 Participants |
| Sitagliptin and Glargine + SSI | Number of Patients With Severe Hypoglycemic Episodes Among the 3 Treatment Groups | 0 Participants |
| Glargine and Lispro + SSI | Number of Patients With Severe Hypoglycemic Episodes Among the 3 Treatment Groups | 0 Participants |
Secondary
Number of Subjects With Acute Renal Failure Among the Three Randomized Groups During Hospitalization
Acute renal failure is defined as a clinical diagnosis of acute renal failure with documented new-onset abnormal renal function (serum creatinine \> 2.2 mg/dL or an increment \> 0.5 mg/dL from baseline). The total daily dose of insulin and sitagliptin will be adjusted as per serum creatinine concentration. The total daily insulin dose will be reduced to 0.3 unit/kg in patients with creatinine \>1.7 mg/dl. The dose of sitagliptin will be reduced to 50 mg/day in patients with creatinine clearance between 30-50 ml/min (approximate serum creatinine levels \>1.7 and ≤3.0 mg/dl for men and \>1.5 and ≤2.5 mg/dl for women).
Time frame: during hospitalization, up to 10 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sitagliptin + SSI Prn | Number of Subjects With Acute Renal Failure Among the Three Randomized Groups During Hospitalization | 0 Participants |
| Sitagliptin and Glargine + SSI | Number of Subjects With Acute Renal Failure Among the Three Randomized Groups During Hospitalization | 0 Participants |
| Glargine and Lispro + SSI | Number of Subjects With Acute Renal Failure Among the Three Randomized Groups During Hospitalization | 0 Participants |
Secondary
Percent of Blood Glucose Readings Within Target Range Between 70 and 140 mg/dL Among the Three Groups After 24 Hrs of Randomized Treatment
The blood glucose within target range is defined as the levels between 70 mg/dL and 140 mg/dL. BG was measured before each meal and at bedtime (or every 6 h if a patient was not eating) using a point-of-care glucose meter (ACCUCHECK; Roche, Indianapolis, IN). In addition, BG was measured at any time if a patient experienced symptoms of hypoglycemia or if requested by the treating physician. the percentage of the readings are calculated and compared
Time frame: during hospitalization, up to 10 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin + SSI Prn | Percent of Blood Glucose Readings Within Target Range Between 70 and 140 mg/dL Among the Three Groups After 24 Hrs of Randomized Treatment | 36 percentage of blood glucose readings | Standard Deviation 30 |
| Sitagliptin and Glargine + SSI | Percent of Blood Glucose Readings Within Target Range Between 70 and 140 mg/dL Among the Three Groups After 24 Hrs of Randomized Treatment | 43 percentage of blood glucose readings | Standard Deviation 28 |
| Glargine and Lispro + SSI | Percent of Blood Glucose Readings Within Target Range Between 70 and 140 mg/dL Among the Three Groups After 24 Hrs of Randomized Treatment | 43 percentage of blood glucose readings | Standard Deviation 26 |