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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Hyperglycemia, Metformin, Type 2 Diabetes, Hyperlactatemia

Intervention / Treatment
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* Drug: Metformin Hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metformin +<br>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. | Drug: Metformin Hydrochloride<br>* Perioperative continuation of oral metformin therapy according to the patient's normal dosage and dosage intervals<br>* Other names: Group A;|
| No Intervention: Metformin -<br>The control group involves no intervention, which means cessation of oral metformin therapy 24 hours prior to surgery according to the local guidelines of the anesthesia department and the national anesthesiology guidelines. | |

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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