Glargine U300 Hospital Trial

Several randomized clinical trials done previously in medicine and surgical patients with T2D have shown that basal bolus regimen with glargine results in a lower mean daily blood glucose (BG) concentrations compared to the sole use of sliding scale regular insulin (SSI) and in lower rate of hospital complications. Glargine U300 results in similar improvement but in lower rate of hypoglycemia than treatment with glargine U100. No previous studies; however, have compared the efficacy and safety of glargine U300 in the management of hyperglycemia and diabetes in the hospital setting. This study will determine if treatment with glargine U300 has a similar glucose control in patients with diabetes admitted to the hospital and if glargine U300 will result in lower number of low blood sugars compared to glargine U100 .

• Glargine U300 (Drug), also known as Toujeo: Glargine U300 is a new generation long-acting insulin.
• Glargine U100 (Drug), also known as Lantus: Glargine U100 is a long-acting insulin.
• Glulisine Insulin (Drug), also known as Apidra: Glulisine is a mealtime insulin taken either 15 minutes before or 20 minutes after a meal.

Primary outcomes

• Mean Daily Blood Glucose Concentration Inpatient [up to 10 days (day of hospital discharge)]: The mean daily blood glucose concentration for all participants will be calculated by taking the average of all pre-meal and bedtime glucose values collected each day after the first day of therapy during the hospital stay.
• Mean Daily Blood Glucose Concentration After Hospital Discharge [assessed from day 11 (day after hospital discharge) up to 3 months]: Subjects will measure their blood sugar levels at home by finger stick before meals two or three times per day and record the readings in a diary. The readings will be averaged for each day and the mean daily blood glucose concentration will be calculated.

Secondary outcomes

• Mean Daily Glucose in Patients With Admission HbA1c Lower Than 8% [up to 3 months post enrollment]: Glycemic control will be measured by mean daily blood glucose concentration for subjects with HbA1c lower than 8% at admission. The average of all pre-meal and bedtime glucose values will be calculated.
• Mean Daily Glucose in Patients With Admission HbA1c Higher Than 8% [up to 3 months post enrollment]: Mean daily blood glucose concentration for subjects with HbA1c higher than 8% at admission will be recorded
• Mean Daily Glucose in Patients With Length of Stay Shorter Than 3 Days [Up to 3 days]: Glycemic control will be conducted by measuring mean daily blood glucose concentration for subjects with length of hospital stay shorter than 3 days
• Mean Daily Glucose in Patients With Length of Stay Shorter Than 5 Days [Up to 5 days]: Glycemic control will be conducted by measuring mean daily blood glucose concentration for subjects with length of hospital stay shorter than 5 days
• Mean Daily Glucose in Patients With Length of Stay Longer Than 5 Days [Up to 10 days]: Glycemic control will be measured by mean daily blood glucose concentration for subjects with length of hospital stay longer than 5 days. The average of daily pre-meal and bedtime glucose values will be calculated.
• Percent of Blood Glucose 70-180 Measured by Point of Care Test [3 months post enrollment]: Percent of Blood Glucose Readings in the 70-180 mg/dL Range Measured by Point of Care Test
• Percent of Subjects With Hypoglycemic Events [3 months post enrollment]: Percent of of subjects with hypoglycemic events (BG < 70 mg/dl) will be recorded.
• Percent of Subjects With Severe Hypoglycemia [3 months post enrollment]: Percent of subjects experiencing severe hypoglycemia (BG <54 mg/dl) will be recorded.
• Number of Days of Hospital Stay [Up to 10 days]: The number of days of hospital stay for each subject will be recorded.
• Number Subjects With Cardiac Complications [3 months post enrollment]: The number of subjects experiencing cardiac cardiac complications will be recorded.
• Number of Patients With Acute Renal Failure [3 months post enrollment]: The number of subjects with a clinical diagnosis with documented new-onset abnormal renal function (increment in serum creatinine > 0.5 mg/dL from baseline).
• Hospital Mortality [During hospital stay - up to 10 days]: Number of hospital deaths that occur.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Males or females between > 18 years admitted to a general medicine or surgical service.
* Known histories of T2D treated with either diet alone, oral monotherapy, any combination of oral antidiabetic agents, short-acting GLP1-RA (exenatide, liraglutide) or insulin therapy with the exception of degludec and glargine U300.
* Subjects must have an admission/randomization BG > 140 mg and < 400 mg/dL without laboratory evidence of diabetic ketoacidosis (bicarbonate < 18 mEq/L, pH < 7.30, or positive serum or urinary ketones).

Exclusion Criteria:

* Subjects with increased BG concentration, but without a known history of diabetes.
* Patients treated with degludec or glargine U300, or with long-acting weekly GLP1-RA (weekly exenatide, dulaglutide or albiglutide).
* Patients with acute critical or surgical illness admitted to the ICU or expected to require admission to the ICU.
* Patients with clinically relevant hepatic disease (diagnosed liver cirrhosis and portal hypertension), corticosteroid therapy, or impaired renal function (eGFR< 30 ml/min).
* Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study.
* Female subjects who are pregnant or breast feeding at time of enrollment into the study.

Participant flow

Outcome results

• Mean Daily Blood Glucose Concentration Inpatient (Primary), Mean, mg/dL: Basal Bolus Insulin With Glargine U300 and Glulisine Insulin 186 +/- 40; Basal Bolus Insulin With Glargine U100 and Glulisine Insulin 184 +/- 46
• Mean Daily Blood Glucose Concentration After Hospital Discharge (Primary), Mean, mg/dL: Basal Bolus Insulin With Glargine U300 and Glulisine Insulin 171.6 +/- 44.8; Basal Bolus Insulin With Glargine U100 and Glulisine Insulin 164.5 +/- 46.7
• Mean Daily Glucose in Patients With Admission HbA1c Lower Than 8% (Secondary), Mean, mg/dL: Basal Bolus Insulin With Glargine U300 and Glulisine Insulin 150 +/- 14.4; Basal Bolus Insulin With Glargine U100 and Glulisine Insulin 134.4 +/- 19.3
• Mean Daily Glucose in Patients With Admission HbA1c Higher Than 8% (Secondary), Mean, mg/dL: Basal Bolus Insulin With Glargine U300 and Glulisine Insulin 152.3 +/- 38.5; Basal Bolus Insulin With Glargine U100 and Glulisine Insulin 155.6 +/- 36.5
• Mean Daily Glucose in Patients With Length of Stay Shorter Than 3 Days (Secondary), Mean, mg/dL: Basal Bolus Insulin With Glargine U300 and Glulisine Insulin 169.71 +/- 42.35; Basal Bolus Insulin With Glargine U100 and Glulisine Insulin 196.72 +/- 56.60
• Mean Daily Glucose in Patients With Length of Stay Shorter Than 5 Days (Secondary), Mean, mg/dL: Basal Bolus Insulin With Glargine U300 and Glulisine Insulin 193.53 +/- 43.1; Basal Bolus Insulin With Glargine U100 and Glulisine Insulin 193.64 +/- 42.6
• Mean Daily Glucose in Patients With Length of Stay Longer Than 5 Days (Secondary), Mean, mg/dL: Basal Bolus Insulin With Glargine U300 and Glulisine Insulin 188.46 +/- 34.7; Basal Bolus Insulin With Glargine U100 and Glulisine Insulin 174.55 +/- 34.1
• Percent of Blood Glucose 70-180 Measured by Point of Care Test (Secondary), Mean, percentage of BG readings: Basal Bolus Insulin With Glargine U300 and Glulisine Insulin 50.3 +/- 27.5; Basal Bolus Insulin With Glargine U100 and Glulisine Insulin 54.9 +/- 29.3
• Percent of Subjects With Hypoglycemic Events (Secondary), Number, percentage of subjects: Basal Bolus Insulin With Glargine U300 and Glulisine Insulin 8.7; Basal Bolus Insulin With Glargine U100 and Glulisine Insulin 9.5
• Percent of Subjects With Severe Hypoglycemia (Secondary), Number, percentage of subjects: Basal Bolus Insulin With Glargine U300 and Glulisine Insulin 0; Basal Bolus Insulin With Glargine U100 and Glulisine Insulin 6
• Number of Days of Hospital Stay (Secondary), Median, days: Basal Bolus Insulin With Glargine U300 and Glulisine Insulin 6 (4 to 8); Basal Bolus Insulin With Glargine U100 and Glulisine Insulin 4 (3 to 7)
• Number Subjects With Cardiac Complications (Secondary), Count of participants, Participants: Basal Bolus Insulin With Glargine U300 and Glulisine Insulin 5; Basal Bolus Insulin With Glargine U100 and Glulisine Insulin 11
• Number of Patients With Acute Renal Failure (Secondary), Count of participants, Participants: Basal Bolus Insulin With Glargine U300 and Glulisine Insulin 1; Basal Bolus Insulin With Glargine U100 and Glulisine Insulin 1
• Hospital Mortality (Secondary), Number, events: Basal Bolus Insulin With Glargine U300 and Glulisine Insulin 0; Basal Bolus Insulin With Glargine U100 and Glulisine Insulin 2

Adverse events

Time frame: 3 months.

Serious adverse events by term

Other adverse events by term

• Results publication: Pasquel FJ, Lansang MC, Khowaja A, Urrutia MA, Cardona S, Albury B, Galindo RJ, Fayfman M, Davis G, Migdal A, Vellanki P, Peng L, Umpierrez GE. A Randomized Controlled Trial Comparing Glargine U300 and Glargine U100 for the Inpatient Management of Medicine and Surgery Patients With Type 2 Diabetes: Glargine U300 Hospital Trial. Diabetes Care. 2020 Jun;43(6):1242-1248. doi: 10.2337/dc19-1940. Epub 2020 Apr 9. PMID 32273271

• Study Protocol and Statistical Analysis Plan (PDF, 2019-01-28)
• Informed Consent Form (PDF, 2019-01-28)

• Guillermo Umpierrez, MD, Principal investigator, Emory University