Metformin ER at Bedtime in Older Adults with Borderline Renal Function
For an older adult with eGFR ≥ 45 mL/min/1.73 m², metformin extended-release should be taken with the evening meal—not at bedtime—and the current dose can be safely continued with increased monitoring every 3–6 months. 1, 2
Optimal Timing for Metformin ER Administration
Metformin extended-release is specifically designed for once-daily administration with the evening meal, not at bedtime. 2, 3 The extended-release formulation provides therapeutic drug levels throughout the day, with peak plasma concentrations occurring 4–8 hours after administration. 4, 5 Taking it with food—particularly the evening meal—maximizes absorption and minimizes gastrointestinal side effects. 6
- The FDA-approved drug label explicitly states that metformin ER should be administered with a meal, preferably the evening meal. 3, 6
- Taking metformin ER at bedtime (without food) reduces bioavailability and increases the risk of gastrointestinal intolerance. 6
- The GelShield Diffusion System technology used in metformin ER requires food for optimal drug release and absorption. 7, 5
Renal Function Considerations at eGFR ≥ 45 mL/min/1.73 m²
At eGFR ≥ 45 mL/min/1.73 m², standard metformin dosing can be continued without mandatory dose reduction, but monitoring frequency must increase to every 3–6 months. 1, 8
eGFR-Based Management Algorithm:
- eGFR ≥ 60 mL/min/1.73 m²: Continue standard dosing (up to 2000 mg daily); monitor annually. 1, 8
- eGFR 45–59 mL/min/1.73 m²: Continue current dose in most patients; consider dose reduction in those with advanced age, liver disease, or heart failure; monitor every 3–6 months. 1, 9, 8
- eGFR 30–44 mL/min/1.73 m²: Reduce dose by 50% (maximum 1000 mg daily); monitor every 3–6 months. 1, 8
- eGFR < 30 mL/min/1.73 m²: Discontinue immediately (absolute contraindication). 1, 8, 3
Special Considerations for Older Adults
Older adults require heightened vigilance even when eGFR is preserved, due to increased risk of gastrointestinal side effects, reduced appetite, and potential for dehydration. 1
- Metformin can cause gastrointestinal side effects and appetite reduction that may be particularly problematic in older adults. 1
- Monitor for vitamin B12 deficiency in patients on metformin for more than 4 years, as approximately 7% develop subnormal levels. 9, 8
- Temporary discontinuation is necessary during acute illness, hospitalizations, or procedures that may compromise renal function. 1
Critical "Sick Day" Rules
Metformin must be held immediately during any acute illness causing volume depletion, regardless of baseline eGFR. 2, 8
- Stop metformin during sepsis, severe infection, marked dehydration, severe diarrhea, or vomiting. 2, 8
- Hold before iodinated contrast procedures in patients with eGFR 30–60 mL/min/1.73 m², history of liver disease, alcoholism, or heart failure; re-check eGFR 48 hours post-procedure before restarting. 8, 3
- Discontinue during hospitalizations with elevated acute kidney injury risk. 2, 8
Common Pitfalls to Avoid
Do not take metformin ER at bedtime without food—this reduces efficacy and increases side effects. 3, 6 The extended-release formulation requires administration with a meal for optimal absorption and tolerability. 6
Do not rely solely on serum creatinine—always calculate eGFR, especially in elderly or small-statured patients, as creatinine-based cutoffs are outdated and may lead to inappropriate discontinuation. 8
Do not discontinue metformin prematurely at eGFR 45–59 mL/min/1.73 m²—this range is well above the threshold requiring cessation, and population studies show reduced mortality with metformin use in this range compared to other glucose-lowering therapies. 8