Diabetes Mellitus
Conditions
Keywords
Hyperglycemia, Insulin therapy, Oral therapy, Basal bolus therapy, Mean daily blood glucose, Hospitalization
Brief summary
This randomized controlled clinical trial will assess whether continuation of home oral antidiabetic agents during hospitalization can be used as a safe and effective alternative to insulin therapy in the management of diabetes in the hospital. The primary outcome of the study is to determine differences in glycemic control as measured by mean daily blood glucose (BG) concentration between oral antidiabetic medications and basal bolus therapy in hospitalized patients with type 2 diabetes (T2D).
Detailed description
Hyperglycemia in the hospital is common and has been associated with increased hospital complications, length of stay, and mortality. Improving glycemic control has been shown to improve length of stay, multi-organ failure, systemic infections, as well as short- and long-term mortality. Clinical guidelines from professional organizations recommend the use of subcutaneous (SQ) insulin as the preferred therapy for glycemic control in general medical and surgical patients with T2D. This approach, however, is labor intensive requiring multiple daily insulin injections, costly, and associated with significant risk of iatrogenic hypoglycemia Over 75% of patients with T2D are treated with oral antidiabetic drugs (OADs) but due to the lack of safety and efficacy data from randomized controlled trials, clinical guidelines recommend stopping OADs during hospitalization. The current clinical guidelines have raised concerns with the use of OADs including risk of hypoglycemia with sulfonylureas, fluid retention and worsening of heart failure with thiazolidinediones, and risk of metformin-associated lactic acidosis in patients with severe renal impairment. However, several observational studies have reported that the use of OADs results in similar glycemic control without increased risk of complications compared to insulin regimens. A recent observational study that included 17,325 hospitalized patients with T2D, found that patients treated with OADs had similar glycemic control without differences in complications and no increase in rates of hypoglycemia compared to those treated with insulin. This study will assess whether continuation of home oral antidiabetic agents during hospitalization can be used as a safe and effective alternative to insulin therapy in the management of diabetes in hospital patients with T2D. For a subset of participants, a CGM device will be placed for the duration of the study to assess parameters of glycemic control and hypoglycemia.
Interventions
DRUGOral Anti-diabetes Drugs alone
OADs will be continued at same outpatient dosage unless contraindicated. Participants will be switched to the preferred drug within the category of medication they take at home. Dose adjustment for OADs will be based on clinical/laboratory status. The OAD will be held if the participant is placed on strict nil per os (NPO) and is unable to take oral medications after enrollment.
DRUGBasal bolus insulin
Basal insulin with glargine or detemir will be used as per the hospital formulary.
DRUGSupplemental insulin
Supplemental (correction) lispro or aspart insulin following the supplemental/sliding scale standard of care protocol for BG \>140 mg/dl.
DEVICEContinuous glucose monitoring (CGM)
A subset of participants will be randomized to take part in an optional study where a CGM device will be placed for the duration of the study. CGM reports will be reviewed at the end of the study to assess parameters of glycemic control and hypoglycemia, and not used for insulin dose adjustment. The Dexcom CGM is a small sensor that inserts just under the skin to continuously monitor glucose levels. Results are transmitted to the wearer's smartphone every five minutes.
Sponsors
Emory University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Males or females, age 18-80 years admitted to a general medicine and surgery services * Known history of T2D receiving OADs either as monotherapy or in combination therapy * Admission BG \< 250 mg/dl or randomization BG \<250 mg/dl and not receiving basal insulin * Patients receiving OADs in combination with GLP-1 receptor agonists (GLP-1RA) who have HbA1c \<7.5% within the past three months * HbA1c \<10%
Exclusion criteria
* No known history of diabetes * Laboratory evidence of diabetic ketoacidosis * Subjects with a history of type 1 diabetes (suggested by BMI \< 25 requiring insulin therapy or with a history of diabetic ketoacidosis, or ketonuria) * Meeting any
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Daily Blood Glucose (BG) Concentration | During hospital stay (up to 10 days) | Mean daily BG concentration is compared between OADs and basal bolus therapy in hospitalized patients with type 2 diabetes (T2D). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Mild Hypoglycemic Events | During hospital stay (up to 10 days) | Mild hypoglycemic events are defined as BG \<70 mg/dl. Hypoglycemic events are assessed by point of care (POC) testing and continuous glucose monitoring (CGM). |
| Number of Clinically Significant Hypoglycemic Events | During hospital stay (up to 10 days) | Clinically significant hypoglycemic events are defined as BG \<54 mg/dl. Hypoglycemic events are assessed by POC testing and CGM. |
| Number of Severe Hypoglycemic Severe (<40 mg/dl) Events | During hospital stay (up to 10 days) | Severe hypoglycemic events are defined as BG \<40 mg/dl. Hypoglycemic events are assessed by POC testing and CGM. |
| Percent of Blood Glucose Values Within Target Range Without Hypoglycemia | During hospital stay (up to 10 days) | The percentage of BG values within the target range of 70-180 mg/dl and without hypoglycemia is compared between study arms. |
| Number of Episodes of Hyperglycemia After the First Day of Treatment | During hospital stay (up to 10 days) | The number of episodes of hyperglycemia (BG \> 280 mg/dl) after the first day of treatment is compared between study arms. |
| Units Per Day of Insulin | During hospital stay (up to 10 days) | The units of insulin administered per day is compared between study arms. |
| Number of Patients Using Specific Oral Antidiabetic Drugs (OADs) During Hospitalization | During hospital stay (up to 10 days) | The number of participants using specific oral antidiabetic drugs (OADs) during hospitalization use was recorded. Some participants used more than one OAD. |
| Number of Patients on OADs Requiring Insulin Rescue Therapy | During hospital stay (up to 10 days) | The number of patients on OADs requiring insulin rescue therapy was recorded |
| Number of Episodes of Treatment Failure | During hospital stay (up to 10 days) | Treatment failure is defined as mean daily BG \> 240 mg/dl or 3 consecutive BG \> 240 mg/dl. |
| Glycemic Variability in Participants Receiving CGM Monitoring | During hospital stay (up to 10 days) | Glycemic variability is measured using the coefficient of variation |
| Percentage of Time Above BG Target Range (>180 mg/dl) in Participants Receiving CGM Monitoring | During hospital stay (up to 10 days) | The percentage of time above BG target range (\>180 mg/dl) is assessed in participants receiving CGM monitoring. |
| Percentage of Time in BG Target Range (70-180 mg/dl) in Participants Receiving CGM Monitoring | During hospital stay (up to 10 days) | The percentage of time in the BG target range (70-180 mg/dl) is assessed in participants receiving CGM monitoring. |
| Percentage of Time Below BG Target Range (BG <70 mg/dl) in Participants Receiving CGM Monitoring | During hospital stay (up to 10 days) | The percentage of time below BG target range (BG \<70 mg/dl) is assessed in participants receiving CGM monitoring. |
| Number of Hospital Complications | During hospital stay (up to 10 days) | Hospital complications are assessed as a composite variable including infectious, renal, pulmonary, neurologic, cardiovascular complications, and mortality. |
| In-hospital Mortality | During hospital stay (up to 10 days) | In-hospital mortality is compared between study arms. |
| Number of Individual Hospital Complications | Up to 40 days (hospital stay plus 30 days after discharge) | Number of individual hospital complications is compared between study arms. The specific complications assessed for this outcome include acute respiratory failure, acute renal failure (incremental rise in creatinine by 0.5 mg/dL from baseline), infection during hospitalization not felt to be present on admission (including wound infection, urinary tract infection, bacteremia), myocardial infarction, cardiac arrhythmia, congestive heart failure, and cardiac arrest. |
| Hospital Costs | During hospital stay (up to 10 days) | Total hospital costs will be compared between study arms. |
| Length of Hospital Stay | During hospital stay (up to 10 days) | Length of hospital stay, in days, is compared between study arms. Participants were engaged in study activities for up to 10 days during hospitalization and the total number of days of hospitalization was obtained from medical records. |
| Costs for Diabetes Specific Therapies | During hospital stay (up to 10 days) | Costs for diabetes specific therapies (including insulin, oral agents, and cost of injection administration) will be compared between study arms. |
| Number of Hospital Re-admissions | within 30 days of hospital discharge | Number of hospital re-admissions within 30 days of hospital discharge are compared between study arms. |
| Number of Emergency Room Visits | within 30 days of hospital discharge | Number of emergency room visits within 30 days of hospital discharge is compared between study arms. |
| Number of Participants Requiring ICU Care | During hospital stay (up to 10 days) | The number of participants transferred to the ICU is compared between study arms. |
| Nursing Antihyperglycemic Drug Preference Survey | Day of hospital discharge (up to 10 days) | The nurse who provided the most care for the participant during hospitalization completed a 7-item survey assessing antihyperglycemic drug preference. Nurses indicate if they agree or disagree with statements related to patient outcomes, workload requirements of insulin therapy, and perceived usefulness and safety of OADs. A summary score is not calculated for this qualitative survey. The number of nurses agreeing with each item are presented here. |
| Patient Antihyperglycemic Drug Preference Survey | Day of hospital discharge (up to 10 days) | Participants completed a 2 to 5-item survey assessing preferences of antihyperglycemic medications while hospitalized. Participants indicate if they agree or disagree with statements about OAD and insulin use during hospital stays, timely administration of insulin, and concerns about low blood sugar. The number of participants agreeing with the survey item are presented here. A summary score is not calculated for this qualitative survey. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMaya Fayfman, MD
Emory University
Participant flow
Recruitment details
Participants were recruited from Emory University Hospital, Emory University Hospital Midtown, and Grady Memorial Hospital in Atlanta, Georgia, USA. Participant enrollment began August 7, 2020 and study assessments during hospital stay were completed by April 11, 2025.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 9 Participants |
| Age, Categorical Between 18 and 65 years | 61 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 37 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 85 Participants |
| Sex: Female, Male Female | 51 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 43 | 4 / 42 |
| other Total, other adverse events | 3 / 43 | 6 / 42 |
| serious Total, serious adverse events | 4 / 43 | 7 / 42 |
Outcome results
None listed