Glargine U300 Hospital Trial

A Randomized Controlled Trial Comparing Glargine U300 and Glargine U100 for the Inpatient and Post-Hospital Discharge Management of Medicine and Surgery Patients With Type 2 Diabetes

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03013985

Enrollment

247

Registered

2017-01-09

Start date

2017-05-17

Completion date

2019-03-22

Last updated

2020-05-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type 2 Diabetes

Keywords

Blood glucose

Brief summary

The purpose of this study is to find out if treatment with Glargine U300 when compared to Glargine U100 will result in similar sugar control in patients with Type 2 Diabetes (T2D), who are admitted to the hospital and then transition at home, after discharge from the hospital.

Detailed description

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 .

Interventions

DRUGGlargine U300

Glargine U300 is a new generation long-acting insulin.

DRUGGlargine U100

Glargine U100 is a long-acting insulin.

DRUGGlulisine Insulin

Glulisine is a mealtime insulin taken either 15 minutes before or 20 minutes after a meal.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.

Countries

United States

Participant flow

Pre-assignment details

Out of 247 consented, 9 were not randomized, 27 failed to start (19 did not receive study medication, 1 had eGFR out of range, 7 had admission BG \>400 mg/dl)

Participants by arm

Arm	Count
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin Subjects treated with insulin prior to admission will receive 80% of the total daily dose (TDD) given as basal bolus insulin regimen with glargine U300 once daily plus rapid-acting glulisine insulin before meals. In insulin-naïve subjects treated with oral agents, the oral antidiabetic drugs will be discontinued and the bolus insulin dose described above will be given. Half of TDD will be given as glargine U300 and half as glulisine. To prevent hypoglycemia, if a subject is not able to eat, the dose of glulisine will be held. Glargine U300: Glargine U300 is a new generation long-acting insulin. Glulisine Insulin: Glulisine is a mealtime insulin taken either 15 minutes before or 20 minutes after a meal.	108
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin Subjects treated with insulin prior to admission will receive 80% of the total daily dose (TDD) given as basal bolus insulin regimen with glargine U100 once daily plus rapid-acting glulisine insulin before meals. In insulin-naïve subjects treated with oral agents, the oral antidiabetic drugs will be discontinued and the bolus insulin dose as described above will be given. Half of TDD will be given as glargine U100 and half as glulisine. To prevent hypoglycemia, if a subject is not able to eat, the dose of glulisine will be held. Glargine U100: Glargine U100 is a long-acting insulin. Glulisine Insulin: Glulisine is a mealtime insulin taken either 15 minutes before or 20 minutes after a meal.	103
Total	211

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Protocol Violation	2	2
Overall Study	Withdrawal by Subject	14	17

Baseline characteristics

Characteristic	Basal Bolus Insulin With Glargine U300 and Glulisine Insulin	Total	Basal Bolus Insulin With Glargine U100 and Glulisine Insulin
Age, Continuous	57.2 years STANDARD_DEVIATION 12.1	56.7 years STANDARD_DEVIATION 12.2	56.3 years STANDARD_DEVIATION 12.4
Race (NIH/OMB) American Indian or Alaska Native	3 Participants	7 Participants	4 Participants
Race (NIH/OMB) Asian	1 Participants	2 Participants	1 Participants
Race (NIH/OMB) Black or African American	68 Participants	132 Participants	64 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) White	35 Participants	69 Participants	34 Participants
Region of Enrollment United States	108 participants	211 participants	103 participants
Sex: Female, Male Female	46 Participants	85 Participants	39 Participants
Sex: Female, Male Male	62 Participants	126 Participants	64 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 108	2 / 103
other Total, other adverse events	10 / 108	18 / 103
serious Total, serious adverse events	21 / 108	21 / 103

Outcome results

Primary

Mean Daily Blood Glucose Concentration After Hospital Discharge

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.

Time frame: assessed from day 11 (day after hospital discharge) up to 3 months

Population: The outpatient has less number of participants compared to the in-hospital part due to a1c less tan required for outpatient part, participants not wanting to continue in the discharge part and/or admission to long term facilities where we were not able to administer study medication.

Arm	Measure	Value (MEAN)	Dispersion
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin	Mean Daily Blood Glucose Concentration After Hospital Discharge	171.6 mg/dL	Standard Deviation 44.8
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin	Mean Daily Blood Glucose Concentration After Hospital Discharge	164.5 mg/dL	Standard Deviation 46.7

Primary

Mean Daily Blood Glucose Concentration Inpatient

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.

Time frame: up to 10 days (day of hospital discharge)

Arm	Measure	Value (MEAN)	Dispersion
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin	Mean Daily Blood Glucose Concentration Inpatient	186 mg/dL	Standard Deviation 40
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin	Mean Daily Blood Glucose Concentration Inpatient	184 mg/dL	Standard Deviation 46

Secondary

Hospital Mortality

Number of hospital deaths that occur.

Time frame: During hospital stay - up to 10 days

Arm	Measure	Value (NUMBER)
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin	Hospital Mortality	0 events
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin	Hospital Mortality	2 events

Secondary

Mean Daily Glucose in Patients With Admission HbA1c Higher Than 8%

Mean daily blood glucose concentration for subjects with HbA1c higher than 8% at admission will be recorded

Time frame: up to 3 months post enrollment

Population: Patients with admission HbA1c higher than 8%

Arm	Measure	Value (MEAN)	Dispersion
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin	Mean Daily Glucose in Patients With Admission HbA1c Higher Than 8%	152.3 mg/dL	Standard Deviation 38.5
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin	Mean Daily Glucose in Patients With Admission HbA1c Higher Than 8%	155.6 mg/dL	Standard Deviation 36.5

Secondary

Mean Daily Glucose in Patients With Admission HbA1c Lower Than 8%

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.

Time frame: up to 3 months post enrollment

Population: subjects with HbA1c lower than 8% at admission

Arm	Measure	Value (MEAN)	Dispersion
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin	Mean Daily Glucose in Patients With Admission HbA1c Lower Than 8%	150 mg/dL	Standard Deviation 14.4
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin	Mean Daily Glucose in Patients With Admission HbA1c Lower Than 8%	134.4 mg/dL	Standard Deviation 19.3

Secondary

Mean Daily Glucose in Patients With Length of Stay Longer Than 5 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.

Time frame: Up to 10 days

Arm	Measure	Value (MEAN)	Dispersion
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin	Mean Daily Glucose in Patients With Length of Stay Longer Than 5 Days	188.46 mg/dL	Standard Deviation 34.7
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin	Mean Daily Glucose in Patients With Length of Stay Longer Than 5 Days	174.55 mg/dL	Standard Deviation 34.1

Secondary

Mean Daily Glucose in Patients With Length of Stay Shorter Than 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

Time frame: Up to 3 days

Arm	Measure	Value (MEAN)	Dispersion
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin	Mean Daily Glucose in Patients With Length of Stay Shorter Than 3 Days	169.71 mg/dL	Standard Deviation 42.35
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin	Mean Daily Glucose in Patients With Length of Stay Shorter Than 3 Days	196.72 mg/dL	Standard Deviation 56.6

Secondary

Mean Daily Glucose in Patients With Length of Stay Shorter Than 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

Time frame: Up to 5 days

Arm	Measure	Value (MEAN)	Dispersion
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin	Mean Daily Glucose in Patients With Length of Stay Shorter Than 5 Days	193.53 mg/dL	Standard Deviation 43.1
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin	Mean Daily Glucose in Patients With Length of Stay Shorter Than 5 Days	193.64 mg/dL	Standard Deviation 42.6

Secondary

Number of Days of Hospital Stay

The number of days of hospital stay for each subject will be recorded.

Time frame: Up to 10 days

Arm	Measure	Value (MEDIAN)
Basal Bolus Insulin With Glargine U300 and Glulisine Insulin	Number of Days of Hospital Stay	6 days
Basal Bolus Insulin With Glargine U100 and Glulisine Insulin	Number of Days of Hospital Stay	4 days

Secondary

Number of Patients With Acute Renal Failure

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).