Randomized Controlled Trial Comparing the Safety and Efficacy of Insulin Glargine and Insulin Degludec in Glucocorticoid Induced Hyperglycemia in Hospitalized Patients
Randomized Controlled Trial Comparing the Safety and Efficacy of Insulin Glargine and Insulin Degludec in Glucocorticoid Induced Hyperglycemia in Hospitalized Patients
Glucocorticoids (GC) represent therapeutic agents of great importance in the treatment and prophylaxis of multiple inflammatory and non-inflammatory conditions. Despite their efficacy, the use of GCs is associated with a variety of side effects, one of the immediate ones being the development of glucocorticoids induced hyperglycemia.
GCs decrease peripheral insulin sensitivity, increase hepatic gluconeogenesis, trigger insulin resistance, as well as inhibit pancreatic insulin production.([1] It has been shown that acute and chronic hyperglycemia that are present in many cases in the hospital setting are important risk factors for prolonged hospital stays, infectious complications, poorer surgical outcomes, and increased mortality.
In-hospital glucocorticoid induced hyperglycemia is usually managed with optimization of oral anti-diabetic drugs and basal bolus insulin, which has been well established over sliding scale insulin as the preferred regimen for GIH. Through this study we aim to compare to different basal insulins, glargine and degludec in terms of their efficacy and safety (hypoglycemic events) in this setting.
This study protocol describes a randomized controlled trial conducted at Max Super Specialty Hospital to compare the safety and efficacy of insulin glargine and insulin degludec in the management of glucocorticoid-induced hyperglycemia (GIH) among hospitalized patients. The study is being undertaken as a DNB thesis in the Department of Endocrinology under the guidance of Dr. Ambrish Mithal and colleagues.
Glucocorticoids are widely used in hospitalized patients for inflammatory, autoimmune, respiratory, infectious, and malignant conditions. However, they commonly cause hyperglycemia by increasing insulin resistance, enhancing hepatic gluconeogenesis, promoting lipolysis and proteolysis, and impairing pancreatic beta-cell insulin secretion. Approximately 40-50% of hospitalized patients receiving steroids develop GIH, which is associated with poor clinical outcomes such as prolonged hospitalization, infections, delayed wound healing, intensive care admission, and increased mortality.
The study aims to compare insulin glargine, a long-acting basal insulin with approximately 24-hour duration, and insulin degludec, an ultra-long-acting basal insulin with about 42-hour duration. Degludec is hypothesized to provide similar glycemic control with fewer hypoglycemic episodes because of its flatter and more stable pharmacokinetic profile.
The primary objective is to compare the efficacy of glargine and degludec in reducing mean glucose levels in patients with GIH. Secondary objectives include comparing the incidence of hypoglycemia and identifying predictors of glycemic control.
The study population includes non-pregnant adults above 18 years with type 2 diabetes or without diabetes who are admitted under Respiratory Medicine and are receiving glucocorticoids equivalent to more than 20 mg and less than 160 mg prednisolone daily. Patients already on basal insulin, those receiving steroids for less than 48 hours, pregnant patients, or patients with diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), or requiring insulin infusion are excluded.
A total of 112 patients (56 per group) will be enrolled and randomized using the SNOSE (Sequentially Numbered Opaque Sealed Envelope) method into either the insulin glargine or insulin degludec group. Both groups will receive the same rapid-acting bolus insulin (insulin aspart).
Insulin Protocol
The insulin regimen is based on body weight and baseline blood glucose levels:
0.5 units/kg/day for blood glucose <140 mg/dL 0.8 units/kg/day for blood glucose 141-200 mg/dL
1 unit/kg/day for blood glucose >200 mg/dL
Patients already on basal-bolus insulin at home receive 130% of their prior total daily dose.
The total insulin dose is divided into:
Basal insulin (40%) using either insulin glargine or insulin degludec administered at 10 AM, 10 PM, or both depending on glycemic profile.
Bolus insulin (60%) using insulin aspart distributed as:
15% before breakfast 20% before lunch 10% before evening snack 15% before dinner
Correctional insulin doses are added or reduced according to pre-meal glucose levels. For glucose above 200 mg/dL, additional insulin is administered incrementally, while doses are reduced for glucose below 100 mg/dL. Separate lower correction scales are used for patients with chronic liver disease (CLD) or chronic kidney disease (CKD) to minimize hypoglycemia risk.
Blood glucose monitoring is performed using both capillary blood glucose (CBG) testing and continuous glucose monitoring (CGM) before meals, at 10 AM and/or 10 PM, and occasionally at 2 AM. Insulin doses are adjusted daily according to hospital protocol.
Hypoglycemia is defined as blood glucose below 70 mg/dL. Mild hypoglycemia is greater than or equal to 54 mg/dl and below 70 mg/dl; and severe hypoglycemia will be defined as <54 mg/dl or hypoglycemia with severe symptoms and requiring third party assistance. It will be managed according to standardized hospital treatment protocols with repeat glucose monitoring every 15 minutes until recovery.
The study duration is 18 months, and outcomes assessed include mean glucose levels, time in range, glycemic variability, and hypoglycemic events over the first five days of steroid therapy.
Inclusion Criteria: