From the Guidelines
Metformin extended-release (ER) for adults is typically initiated at 500 mg once daily with the evening meal, which can be gradually increased to minimize gastrointestinal side effects, as recommended by the most recent guidelines 1. The dose can be titrated by adding 500 mg weekly based on glycemic response and tolerability, up to a maximum recommended daily dose of 2000 mg. Some key points to consider when prescribing metformin ER include:
- Most patients are effectively managed on 1000-2000 mg once daily.
- Metformin ER should be taken with food to reduce gastrointestinal side effects and should be swallowed whole, not crushed or chewed.
- Renal function should be assessed before starting therapy, with dosage adjustments needed for patients with reduced kidney function (avoid if eGFR <30 mL/min/1.73m²) 1.
- Metformin ER works by decreasing hepatic glucose production, reducing intestinal glucose absorption, and improving insulin sensitivity.
- The extended-release formulation allows for once-daily dosing, which may improve adherence compared to immediate-release metformin that requires multiple daily doses.
- Patients should be monitored for potential side effects including diarrhea, nausea, abdominal discomfort, and the rare but serious lactic acidosis.
- It is also important to monitor vitamin B12 levels in patients taking metformin for more than 4 years, as metformin use is associated with an increased risk of vitamin B12 deficiency and worsening of symptoms of neuropathy 1.
From the FDA Drug Label
A 24-week, double-blind, randomized study of metformin hydrochloride extended-release tablets, taken twice daily (with breakfast and evening meal), was conducted in patients with type 2 diabetes mellitus who had been treated with metformin hydrochloride tablets 500 mg twice daily for at least 8 weeks prior to study entry The results are shown in Table 11 Table 11:Mean Changes from Baseline *in HbA1c and Fasting Plasma Glucose at Week 24 comparing Metformin Hydrochloride Tablets vs Metformin Hydrochloride Extended-Release Tablets in Patients with Type 2 Diabetes Mellitus †an=68 Metformin Hydrochloride Tablets 500 mg Twice Daily Metformin Hydrochloride Extended – release Tablets 1000 mg Once Daily 1500 mg Once Daily
The dosing for Metformin ER in adults is as follows:
- 1000 mg once daily
- 1500 mg once daily 2
From the Research
Metformin ER Dosing in Adults
- The maximum recommended dose of metformin ER is 2000 mg, while the most effective daily dose is between 1500-2000 mg 3
- Metformin ER can be used in patients with reduced kidney function, and its use has been associated with a decreased likelihood of kidney events or death compared to sulfonylureas 4, 5
- In patients with chronic kidney disease (CKD), metformin use is associated with lower risk for all-cause mortality, cardiovascular events, and major hypoglycemic episodes compared to sulfonylureas 5
- The presence of CKD can affect the dosing of metformin, and dose reduction may be necessary in patients with moderate or worse renal impairment 6
Considerations for Metformin ER Dosing
- The time-to-peak change in HbA1c levels for metformin ER is between 25-39 weeks 3
- Metformin ER is generally well-tolerated, but side effects can include gastrointestinal symptoms, and hypoglycemia is rare 7
- Metformin ER can be used in combination with other anti-diabetic agents, including sulfonylureas, pioglitazone, and insulin 3, 6
- Prescribing metformin ER at the most effective dose rather than the maximum recommended dose may help avoid negative dose-related outcomes 3