Linagliptin Inpatient Trial

Study Overview
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Brief Summary
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This study is a prospective, randomized, open label trial to compare the safety and efficacy of linagliptin (an oral anti diabetic medication) given orally once daily to an insulin regimen of glargine once daily plus rapid-acting insulin before meals. Both of these treatment groups will be given corrective doses of rapid-acting insulin analogs (aspart, lispro or glulisine) before meals if their blood sugars are > 140 mg/dl. The patients will be monitored for their blood sugars while the hospital. If patients are agreeable to participate in the discharge part of the study, the investigators will randomized them to a treatment group based on their admission HbA1c. The investigators will follow these patients for 3 months with phone calls and clinic visits, and will monitor their blood sugars. This is to compare the efficacy of linagliptin and our discharge treatment algorithm in controlling blood sugars as out patients.

Detailed Description
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Specific Aim 1: To determine whether in-hospital glycemic control, as measured by mean daily glucose concentration and frequency of hypoglycemic events, is different between treatment with linagliptin (Tradjenta®) plus correction doses with a rapid-acting insulin analog before meals and a basal bolus regimen with glargine once daily and rapid-acting insulin analog before meals in general surgery patients with T2D. Specific Aim 2: To determine the efficacy and safety of an A1C based discharge algorithm in controlling BG after discharge in patients with T2D. Patients who participate in the in-hospital arm (Aim 1) will be invited to enroll in this open label prospective outpatient study. The total duration of the study is 3 months.

Official Title
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Linagliptin Inpatient Trial: A Randomized Controlled Trial on the Safety and Efficacy of Linagliptin (Tradjenta®) Therapy for the Inpatient Management of General Surgery Patients With Type 2 Diabetes

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Linagliptin
* Drug: Basal Bolus
* Drug: Linagliptin
* Drug: Linagliptin + 50% Glargine dose on discharge
* Drug: Linagliptin + 80% Glargine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or female surgical non-ICU patients ages between18 and 80 years A known history of T2D > 1 month, receiving either diet alone, oral antidiabetic agents: sulfonylureas and metformin as monotherapy or in combination therapy (excluding DPP-4 inhibitors) or low-dose (≤ 0.5 units/kg/day) insulin therapy. Subjects with a BG >140 mg and < 400 mg/dL at time of randomization without laboratory evidence of diabetic ketoacidosis (serum bicarbonate < 18 mEq/L or positive serum or urinary ketones) Exclusion Criteria: Age < 18 or > 80 years. Subjects with increased BG concentration, but without a history of diabetes (stress hyperglycemia). 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) (43). Treatment with dipeptidyl peptidase-4 (DPP4) inhibitor or Glucagon-like peptide-1 (GLP1) analogs during the past 3 months prior to admission. Acute critical illness or coronary artery bypass graft (CABG) surgery expected to require admission to a critical care unit. Subjects with gastrointestinal obstruction or adynamic ileus or those expected to require gastrointestinal suction. Patients with clinically relevant pancreatic or gallbladder disease. Patients with previous history of pancreatitis Patients with acute myocardial infarction, clinically significant hepatic disease or significantly impaired renal function (GFR < 30 ml/min). Chronic use of steroid with total daily dose (prednisone equivalent) >5 mg/day 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 into the study. Patients who received supplemental sliding scale insulin >72 hours prior to randomization Patients who received basal insulin > 48 hours prior to randomization

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Linagliptin In-hospital<br>Linagliptin once daily+ correction doses of aspart or lispro if needed | Drug: Linagliptin<br>* Linagliptin once daily + correction doses of rapid acting insulin if needed<br>* Other names: Tradjenta;|
| Active Comparator: Basal Bolus In-hospital<br>Glargine once daily and rapid-acting insulin before meals + correction doses of aspart or lispro if needed | Drug: Basal Bolus<br>* Basal bolus regimen with glargine once daily and rapid-acting insulin (lispro or aspart) before meals + + correction doses of rapid acting insulin if needed<br>* Other names: Glargine (Lantus) + aspart (Novolog) or lispro (Humalog);|
| Experimental: Linagliptin on discharge<br>Patients with admission A1C < 7% will be discharged on same pharmacologic regimen (oral agents, insulin therapy) or linagliptin 5 mg/day. If contraindication to oral anti-diabetics (OAD), discharge patient on linagliptin once daily. | Drug: Linagliptin<br>* Patients with admission A1C < 7% will be discharged on same pharmacologic regimen (oral agents, insulin therapy) or linagliptin 5 mg/day for 3 months.<br>* Other names: Trajenta;|
| Experimental: Linagliptin+50%Glargine dose on d/c<br>Patients with admission HbA1c between 7% and 9% will be discharged on previous oral anti-diabetic agents plus linagliptin, and consider glargine insulin at 50% of daily hospital dose. Patient who did not receive glargine in the hospital, discharge on previous OAD + linagliptin once daily, and consider starting glargine at 0.15 unit/kg/day. | Drug: Linagliptin + 50% Glargine dose on discharge<br>* Patients with admission HbA1c between 7% and 9% will be discharged on previous oral anti-diabetic agents plus linagliptin, and consider glargine insulin at 50% of daily hospital dose for 3 months.<br>* Other names: Trajenta, Lantus;|
| Experimental: Linagliptin+80%Glargine dose on d/c<br>Patients with admission HbA1c ≥ 9% will be discharged on previous oral anti-diabetic agents plus linagliptin, and consider glargine insulin at 80% of daily hospital dose. Patient who did not receive glargine in the hospital, discharge on previous OAD + linagliptin once daily, and consider starting glargine at 0.15 unit/kg/day. | Drug: Linagliptin + 80% Glargine<br>* Patients with admission HbA1c ≥ 9% will be discharged on previous oral anti-diabetic agents plus linagliptin, and consider glargine insulin at 80% of daily hospital dose for 3 months.<br>* Other names: Trajenta, Lantus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in Glycemic Control | Determine differences in glycemic control as measured by mean daily BG concentration between linagliptin alone and basal bolus therapy group. | Inpatient (average 5 days) and outpatient up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypoglycemia <70 mg/dl | Subjects with Hypoglycemia <70 mg/dl | Inpatient (average 5 days) and outpatient up to 12 weeks | 
| Hyperglycemia | Subjects with BG > 300 mg/dl | Inpatient (average 5 days) and outpatient up to 12 weeks | 
| Daily Dose of Insulin | Total daily dose of insulin | Inpatient (average 5 days) and outpatient up to 12 weeks | 
| Length of Hospital Stay | Length of hospital stay (ONLY for inpatient arms 1 and 2) | During Hospitalization | 
| Number of Participants Requiring ICU Care During Hospitalization | Need for intensive care unit (ICU) care (transfer to ICU) during hospitalization | During Hospitalization-average 5 days | 
| Hospital Complications | Subjects with composite complication (ONLY for inpatient arms 1 and 2) | During Hospitalization-average 5 days | 
| Acute Renal Failure During Hospitalization | Subjects with Acute renal failure (ONLY for inpatient arms 1 and 2) | During Hospitalization-average 5 days | 
| Hospital Mortality | Hospital mortality (ONLY in-patient). Mortality is defined as death occurring during hospital stay. | During Hospitalization-average 5 days | 
| Fasting BG Concentration | Average - per hospital stay - fasting BG concentration (for in-hospital groups), and average - per outpatient follow-up period - fasting BG concentration (for discharge groups) | During Hospitalization (average 5 days) and outpatient up to 12 weeks | 
| Subjects With Wound and Other Infections | Subjects with wound and other infections. | During Hospitalization and outpatient up to 12 weeks | 
| HbA1c Level | HbA1c level at admission (for in-patient arms) and HbA1c level at 12-week follow-up outpatient visit (for discharge arms). | Admission to the hospital and 12-week follow-up outpatient visit | 
| Hypoglycemia < 40 mg/dl | Subjects with Hypoglycemia < 40 mg/dl | Inpatient and up to 12 weeks outpatient | 
| Emergency Room Visits | Number of ER visits ONLY for outpatient arms 3,4, and 5. | 3 months after discharge | 
| Subjects With Surgical Reinterventions | Subjects with surgical re-interventions. | Inpatient and up to 12 weeks outpatient | 
| Outpatient Mortality | Deaths among patients after hospital discharge. | 3 months after discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Linagliptin, hospital hyperglycemia, inpatient diabetes