Diabetes Mellitus, Lactic Acidosis
Conditions
Keywords
Lactic acidosis, Contrast media, Angiography, Diabetic, Metformin
Brief summary
The purpose of this study is to determine whether metformin causes lactic acidosis in diabetic patients with preserved kidney function, undergoing coronary angiography or angioplasty with new contrast media. In other words is it necessary to discontinue metformin before these procedures, even when Iodixanol is used as contrast media, which is isosmolar agent and much more safer than urografin which was the main agent in the previous studies that were the base of present guidelines?
Detailed description
Although metformin is not directly nephrotoxic, it has been postulated that can impair gluconeogenesis from lactate, which may lead to lactate accumulation under circumstances such as acute renal failure. In diabetic patients receiving metformin, this condition can be encountered in the setting of acute renal failure following contrast media administration, during coronary angiography i.e. contrast-induced nephropathy. As a result, it has been a part of routine clinical practice to discontinue metformin before angiography to prevent metformin-associated lactic acidosis (MALA). However, there is no general consensus regarding the incidence of MALA and evidence for such intervention is poor. On the other hand, discontinuation of metformin can be associated with detrimental effects on glycemic control and thereby may increase cardiovascular risk in diabetic patients undergoing percutaneous coronary interventions. Consequently, questions have been raised recently regarding the routine discontinuation of metformin, in low-risk patients undergoing coronary angiography. The present study was designed to assess the role of metformin in lactate production in a group of diabetic patients with normal renal function; and to address the questions about significance of routine discontinuation of metformin in low risk patients undergoing coronary angiography. Iodixanol will be the only contrast media in all patients, because of its low nephrotoxicity. Serum blood urea nitrogen and creatinin; as well as arterial blood gases will be evaluated prior to angiography, and repeated 24 and 48 hours after the procedure. Glomerular filtration rate (GFR) is calculated using Cockcroft-Gault formula {GFR= 0.85 (for women)}. Contrast-induced acute kidney injury is defined as a 25-50% or 0.3-0.5 mg/dl net increase in creatinine concentration compared to the baseline values. Metformin-associated lactic acidosis (MALA) is defined as an arterial pH (potential of hydrogen)\<7.35 and plasma lactate concentration \>5 mmol⁄L. In the M (-) group metformin will re-started 48 hours after angiography, albeit in the absence of evidence of lactic acidosis and GFR of \>60 mL/min per 1.73 m2. A written informed consent is taken from all participants and institutional review board has already approved the trial.
Interventions
DRUGMetformin
Incidence of lactic acidosis in diabetic patients receiving contrast media in the presence of metformin.
Sponsors
Shahid Beheshti University of Medical Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Diabetic patients receiving metformin who were scheduled for: * coronary angiography * coronary angioplasty
Exclusion criteria
* Patients who had contraindication for metformin administration, such as: * decompensated heart failure * severe liver disease * severe hypoxemia * GFR\<60 mL/min per 1.73 m2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Lactic Acidosis | 48 hrs | Metformin-associated lactic acidosis (MALA) was defined as an arterial pH \<7.35 and plasma lactate concentration \>5 mmol ⁄ L. |
| Change of Baseline Creatinine 48 hr After Recieving Contrast Media in the Presence or Absence of Metformin Use. | 48 hours from the baseline | — |
Countries
Iran
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| On-metformin Diabetic patients receiving contrast media without discontinuing metformin.
Metformin: Incidence of lactic acidosis in diabetic patients receiving contrast media in the presence of metformin. | 83 |
| Off-metformin Diabetic patients receiving contrast media with discontinuation of metformin. | 79 |
| Total | 162 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 4 |
Baseline characteristics
| Characteristic | On-metformin | Off-metformin | Total |
|---|---|---|---|
| Age, Continuous | 61.57 years | 60.1 years | 60.9 years |
| Sex: Female, Male Female | 43 Participants | 40 Participants | 83 Participants |
| Sex: Female, Male Male | 40 Participants | 39 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 83 | 0 / 79 |
| serious Total, serious adverse events | 0 / 83 | 0 / 79 |
Outcome results
Primary
Change of Baseline Creatinine 48 hr After Recieving Contrast Media in the Presence or Absence of Metformin Use.
Time frame: 48 hours from the baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| On-metformin | Change of Baseline Creatinine 48 hr After Recieving Contrast Media in the Presence or Absence of Metformin Use. | 1.05 mg/dl | Standard Deviation 0.116 |
| Off-metformin | Change of Baseline Creatinine 48 hr After Recieving Contrast Media in the Presence or Absence of Metformin Use. | 0.99 mg/dl | Standard Deviation 0.159 |
Primary
Incidence of Lactic Acidosis
Metformin-associated lactic acidosis (MALA) was defined as an arterial pH \<7.35 and plasma lactate concentration \>5 mmol ⁄ L.
Time frame: 48 hrs
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| On-metformin | Incidence of Lactic Acidosis | 0 participants |
| Off-metformin | Incidence of Lactic Acidosis | 0 participants |