Oral Anti Diabetic Agents in the Hospital

Diabetes Mellitus Clinical Trial

Official title:

Use of Oral Antidiabetic Agents in Hospitalized Patients With Diabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04416269
• Other study ID #: IRB00117027
• Secondary ID: 1K23DK124647-01
• Status: Recruiting
• Phase: Phase 4
• Start date: August 7, 2020
• Est. completion date: December 1, 2024

Study information

• Verified date: June 2023
• Source: Emory University
• Contact: Maya Fayfman, MD
• Phone: 404-778-1664
• Email: maya.fayfman[@]emory.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 concentration between oral antidiabetic medications and basal bolus therapy in hospitalized patients with type 2 diabetes (T2D).

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 (50 patients per group), a CGM devise will be placed for the duration of the study to assess parameters of glycemic control and hypoglycemia.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 260
• Est. completion date: December 1, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 exclusion criteria based on specific contraindications to their home oral therapy

• Acute critical illness or cardiac surgery expected to require admission to a critical care unit

• Gastrointestinal obstruction, adynamic ileus, or expected to require gastrointestinal suction

• Medical or surgical patients expected to be kept NPO for >24-48 hours after admission or after completion of surgical procedure

• Impaired renal function (eGFR <30 ml/min)

• Current treatment with oral or injectable corticosteroid

• Mental condition rendering the subject unable to understand the nature and scope of the study

• Female subjects who are pregnant or breastfeeding at time of enrollment in the study

• New or recent onset (within two weeks) of coronavirus disease 2019 (COVID-19) infection at the time of admission

Related Conditions & MeSH terms

• Diabetes Mellitus

Intervention

Drug:
• Oral 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.
• Basal bolus insulin
Basal insulin with glargine or detemir will be used as per the hospital formulary.
• Supplemental insulin
Supplemental (correction) lispro or aspart insulin following the supplemental/sliding scale standard of care protocol for BG >140 mg/dl.

Device:
• Continuous glucose monitoring (CGM)
A subset of participants (50 per study arm) 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.

Locations

Country	Name	City	State
United States	Emory University Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Grady Memorial Hospital	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean daily BG concentration	Mean daily BG concentration will be compared between OADs and basal bolus therapy in hospitalized patients with T2D.	During hospital stay (up to 10 days)
Secondary	Number of mild hypoglycemic events	Mild hypoglycemic events are defined as BG <70 mg/dl. Hypoglycemic events are assessed by point of care (POC) testing and continues glucose monitoring (CGM).	During hospital stay (up to 10 days)
Secondary	Number of clinically significant hypoglycemic events	Clinically significant hypoglycemic events are defined as BG <54 mg/dl. Hypoglycemic events are assessed by POC testing and CGM.	During hospital stay (up to 10 days)
Secondary	Number of severe hypoglycemic severe (<40 mg/dl) events	Severe hypoglycemic events are defined as BG <40 mg/dl. Hypoglycemic events are assessed by POC testing and CGM.	During hospital stay (up to 10 days)
Secondary	Percent of BG within target range without hypoglycemia	The percentage of BG values within the target range of 70-180 mg/dl and without hypoglycemia will be compared between study arms.	During hospital stay (up to 10 days)
Secondary	Number of episodes of hyperglycemia after the first day of treatment	The number of episodes of hyperglycemia (BG > 280 mg/dl) after the first day of treatment will be compared between study arms.	During hospital stay (up to 10 days)
Secondary	Daily dose of insulin	The total daily dose of insulin will be compared between study arms.	During hospital stay (up to 10 days)
Secondary	Number of patients using oral antidiabetic drugs (OADs) during hospitalization	The number of participants using OADs during hospitalization use will be recorded.	During hospital stay (up to 10 days)
Secondary	OAD dose used during hospitalization	Dosage of OADs used during hospitalization will be recorded.	During hospital stay (up to 10 days)
Secondary	Number of patients on OADs requiring insulin rescue therapy	The number of patients on OADs requiring insulin rescue therapy will be recorded	During hospital stay (up to 10 days)
Secondary	Number of episodes of treatment failure	Treatment failure is defined as mean daily BG > 240 mg/dl or 3 consecutive BG > 240 mg/dl.	During hospital stay (up to 10 days)
Secondary	Glycemic variability in participants receiving CGM monitoring	Glycemic variability will be measured using the coefficient of variation	During hospital stay (up to 10 days)
Secondary	Time above BG target range (>180 mg/dl) in participants receiving CGM monitoring	The percentage of time above BG target range (>180 mg/dl) will be assessed in participants receiving CGM monitoring.	During hospital stay (up to 10 days)
Secondary	Time in BG target range (70-180 mg/dl) in participants receiving CGM monitoring	The percentage of time in the BG target range (70-180 mg/dl) will be assessed in participants receiving CGM monitoring.	During hospital stay (up to 10 days)
Secondary	Time below BG target range (BG <70 mg/dl) in participants receiving CGM monitoring	The percentage of time below BG target range (BG <70 mg/dl) will be assessed in participants receiving CGM monitoring.	During hospital stay (up to 10 days)
Secondary	Number of hospital complications	Hospital complications is assessed as a composite variable including infectious, renal, pulmonary, neurologic, cardiovascular complications, and mortality.	During hospital stay (up to 10 days)
Secondary	In-hospital mortality	In-hospital mortality will be recorded will be compared between study arms.	During hospital stay (up to 10 days)
Secondary	Number of individual hospital complications	Number of individual hospital complications will be 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.	Up to 40 days (hospital stay plus 30 days after discharge)
Secondary	Hospital costs	Total hospital costs will be compared between study arms.	During hospital stay (up to 10 days)
Secondary	Length of hospital stay	Length of hospital stay, in days, will be compared between study arms.	During hospital stay (up to 10 days)
Secondary	Costs for diabetes specific therapies	Costs for diabetes specific therapies (including insulin, oral agents, and cost of injection administration) will be compared between study arms.	During hospital stay (up to 10 days)
Secondary	Number of hospital re-admissions	Number of hospital re-admissions within 30 days of hospital discharge will be compared between study arms.	within 30 days of hospital discharge
Secondary	Number of emergency room visits	Number of emergency room visits within 30 days of hospital discharge will be compared between study arms.	within 30 days of hospital discharge
Secondary	Number of participants requiring ICU care	The number of participants transferred to the ICU will be compared between study arms.	During hospital stay (up to 10 days)
Secondary	Nursing antihyperglycemic drug preference survey	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.	Day of hospital discharge (up to 10 days)
Secondary	Patient antihyperglycemic drug preference survey	Participants will complete 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. A summary score is not calculated for this qualitative survey.	Day of hospital discharge (up to 10 days)