Perioperative Insulin, GIK or GLP-1 Treatment in Diabetes Mellitus (PILGRIM)

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Status: Completed

Conditions: Diabetes Mellitus Type II

Treatments: Drug: GIK infusion; Drug: Liraglutide; Drug: Insulin bolus

Study type: Interventional

Funder types: Other

Identifiers

NCT02036372

NL 41467.018.12

Details and patient eligibility

About

The incidence of diabetes mellitus type II is increasing. More and more patients who need surgery have diabetes mellitus type II. Despite an enormous amount of glucose lowering protocols and the proven negative effects of hyperglycaemia. There is no evidence for the optimal glucose lowering protocol.

This study investigates the optimal intraoperative treatment algorithm to lower glucose in patients with diabetes mellitus type 2 undergoing non-cardiac surgery, comparing intraoperative glucose-insulin-potassium infusion (GIK), insulin bolus regimen (BR) and GLP-1 (liraglutide, LG) treatment.

Full description

Diabetes mellitus is associated with poor outcome after surgery. The prevalence of diabetes in hospitalised patients is up to 40%, meaning that the anaesthesiologist will encounter a diabetes patient in the operating room on a daily basis. Multiple protocols for perioperative glucose regulation have been developed, ranging from intravenous glucose-insulin-potassium infusion to subcutaneous bolus regimens. Despite this abundance of published glucose lowering protocols and the proven negative effects of intraoperative hyperglycaemia in diabetes, there is no evidence regarding the optimal intraoperative glucose lowering treatment. Recently, incretins have been introduced to lower blood glucose. The main hormone of the incretin system is glucagon-like peptide-1 (GLP-1). GLP-1 increases insulin and decreases glucagon secretion in a glucose-dependent manner, resulting in low incidence of hypoglycaemia. This study investigates for the first time the optimal intraoperative treatment algorithm to lower glucose in patients with diabetes mellitus undergoing non-cardiac surgery.

Objective:

This study investigates the optimal intraoperative treatment algorithm to lower glucose in patients with diabetes mellitus type 2 undergoing non-cardiac surgery, comparing intraoperative glucose-insulin-potassium infusion (GIK), insulin bolus regimen (BR) and GLP-1 (liraglutide, LG) treatment.

Enrollment: 150 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Signed informed consent
• known diabetes mellitus type II for > 3 months
• aged 18-75 years
• scheduled for elective non-cardiac surgery

Exclusion criteria

• Daily insulin dosage of > 1 IU/kg body weight

• Oral corticosteroid use
• Planned for day-care (ambulant) surgery
• Planned ICU stay post-operatively
• Planned bowel surgery
• History of chronic pancreatitis or idiopathic acute pancreatitis
• Impaired renal function defined as serum-creatinine ≥ 133 μmol/L for males and ≥ 115 μmol/L for females
• Females of child bearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive measures as required by local law or practice)
• Known or suspected allergy to trial product(s) or related products
• Any condition that the local investigator feels would interfere with trial participation or the evaluation of results

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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150 participants in 3 patient groups

BR (bolus regimen)

Experimental group

Description:

* Day before surgery: half evening dose long acting insulin * Day of surgery: * patients using mealtime and longacting insulin/NPH: withhold mealtime morning dose, stop glucose lowering tablets * patients using only long acting insulin/NPH: half dose of long-acting or NPH insulin, stop glucose lowering tablets * Measure blood glucose every 60 minutes, start 30 min prior to surgery * Give bolus of insulin according to treatment algorithm

Treatment:

Drug: Insulin bolus

LG (Liraglutide)

Experimental group

Description:

* Day before surgery: half dose of long acting and mealtime insulin from start liraglutide * Day of surgery: withhold own insulin, stop oral glucose lowering tablets * Start with 0.6 mg liraglutide subcutaneously (s.c.) the day prior to surgery at 17.00hr. * In case of nausea graded higher than minimal, the patient will be excluded from the study * Otherwise, treatment will be continued with 1.2 mg liraglutide s.c. per day on the day of surgery at 07.00hr. * Measure glucose every 60 minutes, start 30 min prior to surgery * Adjust according to bolus algorithm of BR group

Treatment:

Drug: Insulin bolus

Drug: Liraglutide

GIK (glucose -insulin - potassium) infusion

Active Comparator group

Description:

* Day before surgery: half evening dose long acting insulin * Day of surgery: stop oral glucose lowering tablets and withhold own insulin. * GIK infusion: 500 cc glucose 5% with insulin and 10 mmol KCL per 500 cc. Start at 83 ml/hr. * Calculate the insulin amount in the GIK infusion according to the formula: I= (PG-7)/(200/W)+8 I=Insulin amount, PG=glucose 30 minutes preoperative, W= body weight in kg * Measure blood glucose every 60 minutes, start 30 min prior to surgery * Adjust glucose \> 8 mmol/l according to treatment algorithm

Treatment:

Drug: GIK infusion