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

Type 2 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04284722
• Other study ID #: 1126/2019
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: February 2020
• Est. completion date: April 2021

Study information

• Verified date: February 2020
• Source: Kepler University Hospital
• Contact: Matthias Noitz, MD
• Phone: +43 (0)5 7680 83 - 78171
• Email: matthias.noitz[@]kepleruniklinikum.at
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 400
• Est. completion date: April 2021
• Est. primary completion date: February 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Hyperglycemia
• Hyperlactatemia
• Metformin
• Type 2 Diabetes

Intervention

Drug:
• Metformin Hydrochloride
Perioperative continuation of oral metformin therapy according to the patient's normal dosage and dosage intervals

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Kepler University Hospital

References & Publications (4)

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. — View 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. — View 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. Review. — View 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;(4):CD002967. doi: 10.1002/14651858.CD002967.pub4. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Incidence hypoglycemia	blood sugar levels < 70mg/dl (3.9mmol/l)	24 hours pre-op until 24 hours post-op
Secondary	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
Secondary	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
Secondary	Perioperative renal function	median serum-creatinine value at 24h pre-op and 24h post-op	24 hours pre-op until 24 hours post-op
Secondary	Hospitalization Duration	median time period from day of surgery until discharge from hospital	up to 4 weeks
Secondary	Mortality	In-Hospital mortality	up to 4 weeks