Clinical trial NCT04284722: Perioperative Continuation of Metformin Therapy in Patients With Typ 2 Diabetes Mellitus Undergoing Non-cardiac Surgery
Official title: Perioperative Continuation of Metformin Therapy in Patients With Typ 2 Diabetes Mellitus Undergoing Non-cardiac Surgery
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hyperglycemia
Metformin
Type 2 Diabetes
Hyperlactatemia
Lead sponsor: Kepler University Hospital
Sponsor class: OTHER
First posted: 2020-02-26
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Perioperative Hyperglycemia
timeFrame: 24 hours pre-op until 24 hours post-op
Secondary outcomes:
measure: Perioperative blood glucose control
timeFrame: 24 hours pre-op until 24 hours post-op
measure: Incidence hypoglycemia
timeFrame: 24 hours pre-op until 24 hours post-op
measure: Perioperative lactate levels
timeFrame: 24 hours pre-op until 24 hours post-op
measure: Incidence of hyperlactatemia
timeFrame: 24 hours pre-op until 24 hours post-op
measure: Perioperative renal function
timeFrame: 24 hours pre-op until 24 hours post-op
measure: Hospitalization Duration
timeFrame: up to 4 weeks
measure: Mortality
timeFrame: up to 4 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Kepler University Hospital -Dpt. of Anesthesiology & Intensive Care Medicine
name: Jens Meier, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hulst AH, Polderman JAW, Ouweneel E, Pijl AJ, Hollmann MW, DeVries JH, Preckel B, Hermanides J. Peri-operative continuation of metformin does not improve glycaemic control in patients with type 2 diabetes: A randomized controlled trial. Diabetes Obes Metab. 2018 Mar;20(3):749-752. doi: 10.1111/dom.13118. Epub 2017 Oct 13.
citation: Gasanova I, Meng J, Minhajuddin A, Melikman E, Alexander JC, Joshi GP. Preoperative Continuation Versus Interruption of Oral Hypoglycemics in Type 2 Diabetic Patients Undergoing Ambulatory Surgery: A Randomized Controlled Trial. Anesth Analg. 2018 Oct;127(4):e54-e56. doi: 10.1213/ANE.0000000000003675.
citation: Kuzulugil D, Papeix G, Luu J, Kerridge RK. Recent advances in diabetes treatments and their perioperative implications. Curr Opin Anaesthesiol. 2019 Jun;32(3):398-404. doi: 10.1097/ACO.0000000000000735.
citation: Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev. 2010 Apr 14;2010(4):CD002967. doi: 10.1002/14651858.CD002967.pub4.