Oral Anti Diabetic Agents in the Hospital

Phase 4

Recruiting

• Conditions: Diabetes Mellitus
• Interventions: Drug: Oral Anti-diabetes Drugs alone; Drug: Basal bolus insulin; Drug: Supplemental insulin; Device: Continuous glucose monitoring (CGM)

• Registration Number: NCT04416269
• Lead Sponsor: Emory University

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

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-06-02
• Study First Submitted QC: 2020-06-02
• Study First Posted: 2020-06-04
• Study Start: 2020-08-07
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-09
• Last Update Posted: 2024-12-12
• Primary Completion: 2025-07-01
• Study Completion: 2025-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 260

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%

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oral Anti-diabetes Drugs (OADs) alone	Supplemental insulin	OADs will be continued at same outpatient dosage unless contraindicated
Oral Anti-diabetes Drugs (OADs) alone	Continuous glucose monitoring (CGM)	OADs will be continued at same outpatient dosage unless contraindicated
Basal bolus insulin	Continuous glucose monitoring (CGM)	Basal insulin with glargine or detemir and rapid-acting insulin (lispro/aspart) will be used as per the hospital formulary. OADs and non-insulin injectable antidiabetic medication will be discontinued on admission.
Oral Anti-diabetes Drugs (OADs) alone	Oral Anti-diabetes Drugs alone	OADs will be continued at same outpatient dosage unless contraindicated
Basal bolus insulin	Basal bolus insulin	Basal insulin with glargine or detemir and rapid-acting insulin (lispro/aspart) will be used as per the hospital formulary. OADs and non-insulin injectable antidiabetic medication will be discontinued on admission.
Basal bolus insulin	Supplemental insulin	Basal insulin with glargine or detemir and rapid-acting insulin (lispro/aspart) will be used as per the hospital formulary. OADs and non-insulin injectable antidiabetic medication will be discontinued on admission.

Primary Outcome Measures

Name	Time	Method
Mean daily BG concentration	During hospital stay (up to 10 days)	Mean daily BG concentration will be compared between OADs and basal bolus therapy in hospitalized patients with T2D.

Secondary Outcome Measures

Name	Time	Method
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.
Glycemic variability in participants receiving CGM monitoring	During hospital stay (up to 10 days)	Glycemic variability will be measured using the coefficient of variation
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 continues glucose monitoring (CGM).
Percent of BG 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 will be compared between study arms.
Daily dose of insulin	During hospital stay (up to 10 days)	The total daily dose of insulin will be compared between study arms.
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.
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 will be compared between study arms.
Number of patients using oral antidiabetic drugs (OADs) during hospitalization	During hospital stay (up to 10 days)	The number of participants using OADs during hospitalization use will be recorded.
OAD dose used during hospitalization	During hospital stay (up to 10 days)	Dosage of OADs used during hospitalization will be recorded.
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) will be assessed in participants receiving CGM monitoring.
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) will be assessed in participants receiving CGM monitoring.
Number of hospital complications	During hospital stay (up to 10 days)	Hospital complications is assessed as a composite variable including infectious, renal, pulmonary, neurologic, cardiovascular complications, and mortality.
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 will be 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.
Number of individual hospital complications	Up to 40 days (hospital stay plus 30 days after discharge)	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.
Length of hospital stay	During hospital stay (up to 10 days)	Length of hospital stay, in days, will be compared between study arms.
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.
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) will be assessed in participants receiving CGM monitoring.
In-hospital mortality	During hospital stay (up to 10 days)	In-hospital mortality will be recorded will be compared between study arms.
Hospital costs	During hospital stay (up to 10 days)	Total hospital costs 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 will be 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 will be 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 will be 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.
Patient antihyperglycemic drug preference survey	Day of hospital discharge (up to 10 days)	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.

Trial Locations

Locations (3)

Emory University Hospital Midtown; 🇺🇸 Atlanta, Georgia, United States

Grady Memorial Hospital; 🇺🇸 Atlanta, Georgia, United States

Emory University Hospital; 🇺🇸 Atlanta, Georgia, United States