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Linagliptin Inpatient Trial

Phase 4
Completed
Conditions
Type 2 Diabetes
Interventions
Registration Number
NCT02004366
Lead Sponsor
Emory University
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
295
Inclusion Criteria
  1. Males or female surgical non-ICU patients ages between18 and 80 years
  2. 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.
  3. 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
  1. Age < 18 or > 80 years.
  2. Subjects with increased BG concentration, but without a 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) (43).
  4. Treatment with dipeptidyl peptidase-4 (DPP4) inhibitor or Glucagon-like peptide-1 (GLP1) analogs during the past 3 months prior to admission.
  5. Acute critical illness or coronary artery bypass graft (CABG) surgery expected to require admission to a critical care unit.
  6. Subjects with gastrointestinal obstruction or adynamic ileus or those expected to require gastrointestinal suction.
  7. Patients with clinically relevant pancreatic or gallbladder disease.
  8. Patients with previous history of pancreatitis
  9. Patients with acute myocardial infarction, clinically significant hepatic disease or significantly impaired renal function (GFR < 30 ml/min).
  10. Chronic use of steroid with total daily dose (prednisone equivalent) >5 mg/day
  11. Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study.
  12. Pregnancy or breast feeding at time of enrollment into the study.
  13. Patients who received supplemental sliding scale insulin >72 hours prior to randomization
  14. Patients who received basal insulin > 48 hours prior to randomization

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Basal Bolus In-hospitalBasal BolusGlargine once daily and rapid-acting insulin before meals + correction doses of aspart or lispro if needed
Linagliptin+50%Glargine dose on d/cLinagliptin + 50% Glargine dose on dischargePatients 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.
Linagliptin+80%Glargine dose on d/cLinagliptin + 80% GlarginePatients 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.
Linagliptin In-hospitalLinagliptinLinagliptin once daily+ correction doses of aspart or lispro if needed
Linagliptin on dischargeLinagliptinPatients 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.
Primary Outcome Measures
NameTimeMethod
Differences in Glycemic ControlInpatient (average 5 days) and outpatient up to 12 weeks

Determine differences in glycemic control as measured by mean daily BG concentration between linagliptin alone and basal bolus therapy group.

Secondary Outcome Measures
NameTimeMethod
Daily Dose of InsulinInpatient (average 5 days) and outpatient up to 12 weeks

Total daily dose of insulin

Number of Participants Requiring ICU Care During HospitalizationDuring Hospitalization-average 5 days

Need for intensive care unit (ICU) care (transfer to ICU) during hospitalization

Hospital MortalityDuring Hospitalization-average 5 days

Hospital mortality (ONLY in-patient). Mortality is defined as death occurring during hospital stay.

Hypoglycemia <70 mg/dlInpatient (average 5 days) and outpatient up to 12 weeks

Subjects with Hypoglycemia \<70 mg/dl

HyperglycemiaInpatient (average 5 days) and outpatient up to 12 weeks

Subjects with BG \> 300 mg/dl

Length of Hospital StayDuring Hospitalization

Length of hospital stay (ONLY for inpatient arms 1 and 2)

Hospital ComplicationsDuring Hospitalization-average 5 days

Subjects with composite complication (ONLY for inpatient arms 1 and 2)

Emergency Room Visits3 months after discharge

Number of ER visits ONLY for outpatient arms 3,4, and 5.

Acute Renal Failure During HospitalizationDuring Hospitalization-average 5 days

Subjects with Acute renal failure (ONLY for inpatient arms 1 and 2)

Fasting BG ConcentrationDuring Hospitalization (average 5 days) and outpatient up to 12 weeks

Average - per hospital stay - fasting BG concentration (for in-hospital groups), and average - per outpatient follow-up period - fasting BG concentration (for discharge groups)

Subjects With Wound and Other InfectionsDuring Hospitalization and outpatient up to 12 weeks

Subjects with wound and other infections.

HbA1c LevelAdmission to the hospital and 12-week follow-up outpatient visit

HbA1c level at admission (for in-patient arms) and HbA1c level at 12-week follow-up outpatient visit (for discharge arms).

Hypoglycemia < 40 mg/dlInpatient and up to 12 weeks outpatient

Subjects with Hypoglycemia \< 40 mg/dl

Subjects With Surgical ReinterventionsInpatient and up to 12 weeks outpatient

Subjects with surgical re-interventions.

Outpatient Mortality3 months after discharge

Deaths among patients after hospital discharge.

Trial Locations

Locations (5)

Boston Medical Center

🇺🇸

Boston, Massachusetts, United States

Grady Memorial Hospital

🇺🇸

Atlanta, Georgia, United States

Rush University Medical Center

🇺🇸

Chicago, Illinois, United States

University of Colorado

🇺🇸

Denver, Colorado, United States

Emory University Hospital

🇺🇸

Atlanta, Georgia, United States

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