Clinical trial NCT04416269: Oral Anti Diabetic Agents in the Hospital
Official title: Use of Oral Antidiabetic Agents in Hospitalized Patients With Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Diabetes Mellitus
Keywords: Hyperglycemia
Insulin therapy
Oral therapy
Basal bolus therapy
Mean daily blood glucose
Hospitalization
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2020-06-04
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean daily BG concentration
timeFrame: During hospital stay (up to 10 days)
Secondary outcomes:
measure: Number of mild hypoglycemic events
timeFrame: During hospital stay (up to 10 days)
measure: Number of clinically significant hypoglycemic events
timeFrame: During hospital stay (up to 10 days)
measure: Number of severe hypoglycemic severe (<40 mg/dl) events
timeFrame: During hospital stay (up to 10 days)
measure: Percent of BG within target range without hypoglycemia
timeFrame: During hospital stay (up to 10 days)
measure: Number of episodes of hyperglycemia after the first day of treatment
timeFrame: During hospital stay (up to 10 days)
measure: Daily dose of insulin
timeFrame: During hospital stay (up to 10 days)
measure: Number of patients using oral antidiabetic drugs (OADs) during hospitalization
timeFrame: During hospital stay (up to 10 days)
measure: OAD dose used during hospitalization
timeFrame: During hospital stay (up to 10 days)
measure: Number of patients on OADs requiring insulin rescue therapy
timeFrame: During hospital stay (up to 10 days)
measure: Number of episodes of treatment failure
timeFrame: During hospital stay (up to 10 days)
measure: Glycemic variability in participants receiving CGM monitoring
timeFrame: During hospital stay (up to 10 days)
measure: Time above BG target range (>180 mg/dl) in participants receiving CGM monitoring
timeFrame: During hospital stay (up to 10 days)
measure: Time in BG target range (70-180 mg/dl) in participants receiving CGM monitoring
timeFrame: During hospital stay (up to 10 days)
measure: Time below BG target range (BG <70 mg/dl) in participants receiving CGM monitoring
timeFrame: During hospital stay (up to 10 days)
measure: Number of hospital complications
timeFrame: During hospital stay (up to 10 days)
measure: In-hospital mortality
timeFrame: During hospital stay (up to 10 days)
measure: Number of individual hospital complications
timeFrame: Up to 40 days (hospital stay plus 30 days after discharge)
measure: Hospital costs
timeFrame: During hospital stay (up to 10 days)
measure: Length of hospital stay
timeFrame: During hospital stay (up to 10 days)
measure: Costs for diabetes specific therapies
timeFrame: During hospital stay (up to 10 days)
measure: Number of hospital re-admissions
timeFrame: within 30 days of hospital discharge
measure: Number of emergency room visits
timeFrame: within 30 days of hospital discharge
measure: Number of participants requiring ICU care
timeFrame: During hospital stay (up to 10 days)
measure: Nursing antihyperglycemic drug preference survey
timeFrame: Day of hospital discharge (up to 10 days)
measure: Patient antihyperglycemic drug preference survey
timeFrame: Day of hospital discharge (up to 10 days)
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Maya Fayfman, MD
role: PRINCIPAL_INVESTIGATOR
References: