Perioperative Continuation of Metformin Therapy in Patients With Typ 2 Diabetes Mellitus Undergoing Non-cardiac Surgery

Phase 4

• Conditions: Type 2 Diabetes; Hyperlactatemia; Hyperglycemia; Metformin
• Interventions: Drug: Metformin Hydrochloride

• Registration Number: NCT04284722
• Lead Sponsor: Kepler University Hospital

Brief Summary

Evaluation of the effect of peri-operative continuation of oral metformin therapy on the incidence of perioperative hyperglycemia compared to standard preoperative cessation of oral metformin therapy 24h before surgery.

Detailed Description

Surgical procedures cause metabolic stress and can impair glucose control especially in patients with diabetes mellitus, which often results in peri-operative hyperglycemia. Peri-operative hyperglycemia is associated with impaired wound healing, secondary wound infections, endothelial dysfunction, sepsis, prolonged hospital stay and higher mortality.

Metformin is still the first line treatment in patients with type 2 diabetes mellitus.

Historically it has been stopped before surgery due to fear of hypoglycemia and metformin induced lactic acidosis. However recent studies have suggested that perioperative continuation of metformin might be safe and patients could benefit from more stable preoperative blood sugar levels.

Prospective studies evaluating the benefit of continuing oral metformin therapy in the perioperative period are rare.

The investigators plan to conduct a prospective, randomized-controlled, unblinded clinical trial where patients with type II diabetes mellitus and oral metformin therapy undergoing non-cardiac surgery will be randomized in either an interventional group or a control group. In the interventional group patients will be instructed to continue their regular metformin dose even on the day of surgery, in contrast to the control group, where the patients will be instructed to stop taking metformin 24h prior to surgery.

All other oral anti-diabetic drugs will be paused according to the local anesthesia guidelines.

The investigators plan to evaluate whether or not continuation of metformin can reduce the incidence of perioperative hyperglycemia and whether or not it is associated with elevation of blood lactate levels.

Study Timeline

• Status Verified: 2020-02
• Study Start: 2020-02
• Study First Submitted: 2020-02-20
• Study First Submitted QC: 2020-02-25
• Last Update Submitted: 2020-02-25
• Study First Posted: 2020-02-26
• Last Update Posted: 2020-02-26
• Primary Completion: 2021-02
• Study Completion: 2021-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

• Age 18-99 years
• Diabetes Mellitus Typ 2
• Oral metformin therapy
• Non cardiac-surgery
• Informed consent

Exclusion Criteria

• Insulin therapy
• Ambulatory surgery
• Preoperative therapy with glucocorticoids (prednisolon or equivalent ≥ 5mg/day for more than 7 days)
• Planned postoperative ICU-stay
• Advanced renal insufficiency (eGFR < 45ml/kg/min)
• Advanced liver cirrhosis or failure (Child-Pugh B or C)
• Alcohol abuse
• Pregnancy,
• Perioperative administration of contrast dye

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Metformin +	Metformin Hydrochloride	The study intervention involves the self-administration of metformin in the same dosage as the patient's regular dosage according to regular dosing schedule and randomization.

Primary Outcome Measures

Name	Time	Method
Incidence of Perioperative Hyperglycemia	24 hours pre-op until 24 hours post-op	blood glucose \>180mg/dl (10mmol/l) and/or necessity of additive administration of insulin s.c. during the time frame

Secondary Outcome Measures

Name	Time	Method
Mortality	up to 4 weeks	In-Hospital mortality
Incidence hypoglycemia	24 hours pre-op until 24 hours post-op	blood sugar levels \< 70mg/dl (3.9mmol/l)
Perioperative blood glucose control	24 hours pre-op until 24 hours post-op	mean plasma glucose at 4 defined dates: 24h pre-op, intra-op, 2hours post-op and 24h post-op
Perioperative lactate levels	24 hours pre-op until 24 hours post-op	mediane lactate levels at 4 defined dates: 24h pre-op, intra-op, 2 hours post-op and 24h post-op
Incidence of hyperlactatemia	24 hours pre-op until 24 hours post-op	blood lactate values \>4mmol/L at least at one of 4 measurement dates: 24h pre-op, intra-op, 2 hours post-op, 24 hours post-op
Perioperative renal function	24 hours pre-op until 24 hours post-op	median serum-creatinine value at 24h pre-op and 24h post-op
Hospitalization Duration	up to 4 weeks	median time period from day of surgery until discharge from hospital