Sitagliptin in Non-Diabetic Patients Undergoing General Surgery

Phase 4

Completed

Conditions: Hyperglycemia

Interventions: Drug: Placebo
Drug: Sitagliptin
Drug: Supplemental insulin (insulin lispro)
Drug: Supplemental insulin (insulin aspart)
Drug: Long acting basal insulin (insulin detemir)
Drug: Long acting basal insulin (insulin glargine)

Registration Number: NCT02741687

Lead Sponsor: Emory University

Brief Summary: The purpose of this study is to compare sitagliptin with a placebo for the prevention of high glucose after general surgery.

Detailed Description: Approximately 30-40% of hospitalized patients will develop stress hyperglycemia (high glucose in response to surgery or illness). High glucose is linked to an increased risk of hospital complications including wound infection, kidney failure and death. Patients with high glucose are treated with insulin given through an arm vein or by frequent insulin injections under the skin. Recent studies have found that inpatient therapy with oral dipeptidyl peptidase-4 inhibitor (DPP4-I) is an effective alternative to insulin in improving glycemic control with low risk of hypoglycemia in general medicine and surgical patients.

Sitagliptin is an oral medication approved by the Food and Drug Administration (FDA) to treat patients with diabetes. The aim of this study is to determine whether treatment with sitagliptin once daily can prevent the development of stress hyperglycemia during the postoperative period in non-diabetic patients undergoing general surgery.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 80

Inclusion Criteria

Undergoing non-cardiac surgery
No previous history of diabetes or hyperglycemia
Fasting blood glucose level of <126 mg/dl
Blood glucose <126mg/dl at the time of randomization (could occur at any time of the day)

Exclusion Criteria

History of hyperglycemia (blood glucose equal to or above 126 mg/dl or HbA1C greater than 6.5%) or previous treatment with oral antidiabetic agents or insulin
Patients undergoing cardiac surgery
Patients anticipated to require ICU care following surgery
Severely impaired renal function (GFR < 30 ml/min) or clinically significant hepatic failure
Moribund patients and those at imminent risk of death (brain death or cardiac standstill)
Patients with gastrointestinal obstruction or adynamic ileus or those expected to require gastrointestinal suction
Patients with clinically relevant pancreatic or gallbladder disease
Treatment with oral (> 5 mg/day) or injectable corticosteroid
Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
Pregnancy or breast-feeding at time of enrollment

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sitagliptin Arm	Supplemental insulin (insulin lispro)	Participants will receive sitagliptin beginning the day prior to surgery and continuing daily during hospitalization (up to 10 days post-surgery). Point of care (POC) testing will be done four times daily, before meals and at bedtime, or every 6 hours for patients who are not eating (NPO). Patients developing hyperglycemia during or after surgery will be treated with insulin per standard of care. Patients with fasting and/or premeal blood glucose levels \>180 mg/dl will receive supplemental insulin provided on a sliding scale. Patients with two consecutive fasting and/or premeal blood glucose levels \>180 mg/dl, or with average daily blood glucose levels \>180 mg/dl will be started on rescue therapy with subcutaneous insulin once daily plus correction doses by a sliding scale.
Sitagliptin Arm	Supplemental insulin (insulin aspart)	Participants will receive sitagliptin beginning the day prior to surgery and continuing daily during hospitalization (up to 10 days post-surgery). Point of care (POC) testing will be done four times daily, before meals and at bedtime, or every 6 hours for patients who are not eating (NPO). Patients developing hyperglycemia during or after surgery will be treated with insulin per standard of care. Patients with fasting and/or premeal blood glucose levels \>180 mg/dl will receive supplemental insulin provided on a sliding scale. Patients with two consecutive fasting and/or premeal blood glucose levels \>180 mg/dl, or with average daily blood glucose levels \>180 mg/dl will be started on rescue therapy with subcutaneous insulin once daily plus correction doses by a sliding scale.
Sitagliptin Arm	Long acting basal insulin (insulin detemir)	Participants will receive sitagliptin beginning the day prior to surgery and continuing daily during hospitalization (up to 10 days post-surgery). Point of care (POC) testing will be done four times daily, before meals and at bedtime, or every 6 hours for patients who are not eating (NPO). Patients developing hyperglycemia during or after surgery will be treated with insulin per standard of care. Patients with fasting and/or premeal blood glucose levels \>180 mg/dl will receive supplemental insulin provided on a sliding scale. Patients with two consecutive fasting and/or premeal blood glucose levels \>180 mg/dl, or with average daily blood glucose levels \>180 mg/dl will be started on rescue therapy with subcutaneous insulin once daily plus correction doses by a sliding scale.
Sitagliptin Arm	Long acting basal insulin (insulin glargine)	Participants will receive sitagliptin beginning the day prior to surgery and continuing daily during hospitalization (up to 10 days post-surgery). Point of care (POC) testing will be done four times daily, before meals and at bedtime, or every 6 hours for patients who are not eating (NPO). Patients developing hyperglycemia during or after surgery will be treated with insulin per standard of care. Patients with fasting and/or premeal blood glucose levels \>180 mg/dl will receive supplemental insulin provided on a sliding scale. Patients with two consecutive fasting and/or premeal blood glucose levels \>180 mg/dl, or with average daily blood glucose levels \>180 mg/dl will be started on rescue therapy with subcutaneous insulin once daily plus correction doses by a sliding scale.
Placebo Arm	Placebo	Participants will receive a placebo tablet beginning the day prior to surgery and continuing daily during hospitalization (up to 10 days post-surgery). Point of care (POC) testing will be done four times daily, before meals and at bedtime, or every 6 hours for patients who are not eating (NPO). Patients developing hyperglycemia during or after surgery will be treated with insulin per standard of care. Patients with fasting and/or premeal blood glucose levels \>180 mg/dl will receive supplemental insulin provided on a sliding scale. Patients with two consecutive fasting and/or premeal blood glucose levels \>180 mg/dl, or with average daily blood glucose levels \>180 mg/dl will be started on rescue therapy with subcutaneous insulin once daily plus correction doses by a sliding scale.
Placebo Arm	Supplemental insulin (insulin lispro)	Participants will receive a placebo tablet beginning the day prior to surgery and continuing daily during hospitalization (up to 10 days post-surgery). Point of care (POC) testing will be done four times daily, before meals and at bedtime, or every 6 hours for patients who are not eating (NPO). Patients developing hyperglycemia during or after surgery will be treated with insulin per standard of care. Patients with fasting and/or premeal blood glucose levels \>180 mg/dl will receive supplemental insulin provided on a sliding scale. Patients with two consecutive fasting and/or premeal blood glucose levels \>180 mg/dl, or with average daily blood glucose levels \>180 mg/dl will be started on rescue therapy with subcutaneous insulin once daily plus correction doses by a sliding scale.
Placebo Arm	Supplemental insulin (insulin aspart)	Participants will receive a placebo tablet beginning the day prior to surgery and continuing daily during hospitalization (up to 10 days post-surgery). Point of care (POC) testing will be done four times daily, before meals and at bedtime, or every 6 hours for patients who are not eating (NPO). Patients developing hyperglycemia during or after surgery will be treated with insulin per standard of care. Patients with fasting and/or premeal blood glucose levels \>180 mg/dl will receive supplemental insulin provided on a sliding scale. Patients with two consecutive fasting and/or premeal blood glucose levels \>180 mg/dl, or with average daily blood glucose levels \>180 mg/dl will be started on rescue therapy with subcutaneous insulin once daily plus correction doses by a sliding scale.
Placebo Arm	Long acting basal insulin (insulin detemir)	Participants will receive a placebo tablet beginning the day prior to surgery and continuing daily during hospitalization (up to 10 days post-surgery). Point of care (POC) testing will be done four times daily, before meals and at bedtime, or every 6 hours for patients who are not eating (NPO). Patients developing hyperglycemia during or after surgery will be treated with insulin per standard of care. Patients with fasting and/or premeal blood glucose levels \>180 mg/dl will receive supplemental insulin provided on a sliding scale. Patients with two consecutive fasting and/or premeal blood glucose levels \>180 mg/dl, or with average daily blood glucose levels \>180 mg/dl will be started on rescue therapy with subcutaneous insulin once daily plus correction doses by a sliding scale.
Placebo Arm	Long acting basal insulin (insulin glargine)	Participants will receive a placebo tablet beginning the day prior to surgery and continuing daily during hospitalization (up to 10 days post-surgery). Point of care (POC) testing will be done four times daily, before meals and at bedtime, or every 6 hours for patients who are not eating (NPO). Patients developing hyperglycemia during or after surgery will be treated with insulin per standard of care. Patients with fasting and/or premeal blood glucose levels \>180 mg/dl will receive supplemental insulin provided on a sliding scale. Patients with two consecutive fasting and/or premeal blood glucose levels \>180 mg/dl, or with average daily blood glucose levels \>180 mg/dl will be started on rescue therapy with subcutaneous insulin once daily plus correction doses by a sliding scale.
Sitagliptin Arm	Sitagliptin	Participants will receive sitagliptin beginning the day prior to surgery and continuing daily during hospitalization (up to 10 days post-surgery). Point of care (POC) testing will be done four times daily, before meals and at bedtime, or every 6 hours for patients who are not eating (NPO). Patients developing hyperglycemia during or after surgery will be treated with insulin per standard of care. Patients with fasting and/or premeal blood glucose levels \>180 mg/dl will receive supplemental insulin provided on a sliding scale. Patients with two consecutive fasting and/or premeal blood glucose levels \>180 mg/dl, or with average daily blood glucose levels \>180 mg/dl will be started on rescue therapy with subcutaneous insulin once daily plus correction doses by a sliding scale.

Primary Outcome Measures

Name	Time	Method
Number of Participants Experiencing Stress Hyperglycemia	Up to time of discharge from hospital, an average of 10 days	The number of participants with at least one episode of stress hyperglycemia. Stress hyperglycemia is defined as a blood glucose \> 180 mg/dL.

Secondary Outcome Measures

Name	Time	Method
Number of Patients Requiring Supplemental, Subcutaneous Insulin	Up to time of discharge from hospital, an average of 10 days	Number of patients requiring subcutaneous insulin, either sliding scale insulin or basal insulin
Total Daily Dose of Insulin for Patients Requiring Supplemental Insulin	Up to time of discharge from hospital, an average of 10 days	Total daily dose of insulin for patients requiring supplemental insulin during surgery and recovery in participants receiving sitagliptin and those receiving the placebo
Length of Hospital Stay	Up to time of discharge from hospital, an average of 10 days	Total length of hospital stay
Number of Participants With Hypoglycemic Events	Up to time of discharge from hospital, an average of 10 days	Number of participants experiencing at least one episode of mild hypoglycemia (blood glucose \< 70 mg/dL) or clinically significant hypoglycemia (blood glucose \< 54 mg/dL)
Number of Patients Transferred to the ICU Immediately After Surgery or During Hospitalization	Up to time of discharge from hospital, an average of 10 days	The number of patients who were transferred to the ICU immediately following surgery or anytime while hospitalized after surgery.
Number of Days in the ICU	Up to time of discharge from hospital, an average of 10 days	The number of days a participant spent in the ICU following surgery, when transfer to the ICU was required.
Number of Participants With Hospital Readmissions After Discharge	Up to 40 days (average time of discharge from the hospital plus 30 days)	Readmissions to the study hospital occurring within 30 days of hospital discharge were documented. There were no follow up phone calls or appointments with participants so any hospital readmissions to hospitals other than the one where the surgery occurred are not known.
Number of Participants With Emergency Room Visits After Discharge	Up to 40 days (average time of discharge from the hospital plus 30 days)	Emergency room visits to the study hospital occurring within 30 days of hospital discharge were documented. There were no follow up phone calls or appointments with participants so any emergency room visits to hospitals other than the one where the surgery occurred are not known.
Number of Participants Experiencing Complications	Up to 40 days (average time of discharge from the hospital plus 30 days)	The number of subjects who experience complications including: wound infection, respiratory failure, pneumonia, acute kidney injury with a rise in creatinine by 38 micromoles/Liter from baseline, major adverse cardiac events, bacterial septic infection, and death. Participants will be followed for 30 days following hospital discharge and all complications will be documented.