From the Guidelines
Metformin and fenofibrate can generally be used together safely, but patients should be monitored for potential side effects, particularly in those with kidney impairment, as fenofibrate may increase the risk of lactic acidosis when used with metformin 1.
Mechanism of Action
These medications work through different mechanisms - metformin improves insulin sensitivity and reduces glucose production in the liver, while fenofibrate lowers triglycerides and increases HDL cholesterol by activating PPAR-alpha receptors.
Benefits and Risks
When used together, they can effectively manage both diabetes and dyslipidemia in patients with metabolic syndrome or diabetes with high triglycerides. However, this combination may slightly increase the risk of hypoglycemia, muscle pain, and lactic acidosis, particularly in patients with kidney impairment.
Monitoring and Precautions
Patients should start with standard dosing (typically metformin 500-1000mg twice daily and fenofibrate 48-145mg daily depending on the formulation) and have their kidney function monitored regularly, with eGFR evaluated before fenofibrate initiation, within 3 months after initiation, and every 6 months thereafter 1.
- Patients should report any unusual muscle pain, weakness, breathing difficulties, or severe stomach pain immediately.
- Staying well-hydrated and temporarily stopping both medications during severe illness, surgery, or procedures using contrast dye is important to reduce risks of adverse effects.
- Fenofibrate should not be used if moderate or severe renal impairment, defined as eGFR <30 mL/min per 1.73 m2, is present 1.
- If eGFR is between 30 and 59 mL/min per 1.73 m2, the dose of fenofibrate should not exceed 54 mg/day 1.
From the FDA Drug Label
Metformin 850 mg three times daily for 10 days Fenofibrate 54 mg1 three times daily for 10 days ↓9% ↓6% Metformin, 850 mg three times daily for 10 days Metformin ↑3% ↑6%
The interaction between metformin and fenofibrate is as follows:
- Fenofibrate decreases metformin exposure by 9% (AUC) and 6% (Cmax).
- Metformin increases fenofibrate exposure by 3% (AUC) and 6% (Cmax) 2.
From the Research
Metformin and Fenofibrate Interactions
- There are no direct studies on the interactions between metformin and fenofibrate in the provided evidence.
- However, the studies provide information on the risks of lactic acidosis associated with metformin use, particularly in patients with renal impairment 3, 4, 5, 6, 7.
- Metformin is known to be contraindicated in patients with severe renal impairment due to the risk of lactic acidosis 3, 6.
- Fenofibrate, a fibric acid derivative, is used to lower cholesterol and triglyceride levels, but its interaction with metformin is not explicitly mentioned in the provided studies.
- Patients with renal impairment should be closely monitored when taking metformin, and the dose should be adjusted accordingly to minimize the risk of lactic acidosis 3, 4, 6.
- The risk of lactic acidosis associated with metformin use increases with decreasing renal function, particularly at an estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73m2 6.
- Metformin should not be used at an eGFR of less than 30 mL/min/1.73m2, according to US Food and Drug Administration guidelines 6.