Would an extended-release (ER) formulation of metformin (biguanide oral hypoglycemic agent) be better tolerated in an 80-year-old female currently taking 1000mg of metformin (biguanide oral hypoglycemic agent) twice daily (BID)?

From the Guidelines

For an 80-year-old female currently taking metformin 1000mg twice daily, switching to metformin extended-release (ER) would likely be more tolerable and potentially work better. I recommend changing to metformin ER 1000mg once daily initially, with the option to increase to 2000mg once daily if needed for glycemic control. Metformin ER is designed to release the medication gradually throughout the day, which typically results in fewer gastrointestinal side effects like nausea, diarrhea, and abdominal discomfort compared to immediate-release formulations, as noted in the 2025 standards of care in diabetes 1. This is particularly beneficial for elderly patients who may be more sensitive to medication side effects. The once-daily dosing of metformin ER also simplifies the medication regimen, which can improve adherence, especially important in older adults who may be taking multiple medications, as discussed in the context of older adults with diabetes 1. The extended-release formulation provides more consistent blood levels of the medication throughout the day, potentially offering more stable glucose control. When making this switch, it's essential to monitor blood glucose levels more frequently initially to ensure adequate glycemic control is maintained with the new formulation. Additionally, considering the patient's age and potential for declining kidney function, it's crucial to monitor eGFR regularly, as recommended in the KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease 1, and adjust the metformin dose accordingly to minimize the risk of lactic acidosis and other complications. Regular monitoring of vitamin B12 levels is also advised, as metformin use is associated with an increased risk of vitamin B12 deficiency, particularly with long-term use 1.

From the FDA Drug Label

Following a single oral dose of metformin hydrochloride extended-release tablets, C max is achieved with a median value of 7 hours and a range of 4 to 8 hours Peak plasma levels are approximately 20% lower compared to the same dose of metformin hydrochloride tablets, however, the extent of absorption (as measured by AUC) is comparable to metformin hydrochloride tablets. The extent of metformin absorption (as measured by AUC) from metformin hydrochloride extended-release tablets at a 2000 mg once-daily dose is similar to the same total daily dose administered as metformin hydrochloride tablets 1000 mg twice daily

The metformin hydrochloride extended-release tablets may be more tolerable for the 80-year-old female patient, as the peak plasma levels are approximately 20% lower compared to the same dose of metformin hydrochloride tablets. However, the extent of absorption is comparable, suggesting that the efficacy may be similar.

• The patient is currently taking 1000mg metformin BID, which is equivalent to a total daily dose of 2000mg.
• The extended-release formulation may provide a more stable and sustained release of the medication, potentially leading to improved tolerability.
• However, it is essential to consult with the patient's healthcare provider to determine the best course of treatment, as individual responses to medication can vary. 2

From the Research

Metformin Formulations and Tolerability

• The extended-release formulation of metformin (MXR) may enhance patient compliance with oral therapy compared to conventional immediate-release metformin (MIR) in type 2 diabetes mellitus (T2DM) 3.
• A study found that patients with T2DM who had been receiving thrice-daily MIR achieved comparable glycemic control when therapy was switched to once- or twice-daily MXR at the same total daily dose 3.
• The MXR formulation was well tolerated with minor gastrointestinal adverse effects, reported by only 3 patients 3.

Gastrointestinal Adverse Events

• Metformin use is associated with a higher risk of gastrointestinal adverse events such as abdominal pain, diarrhea, and nausea compared to control 4.
• The risk of bloating and diarrhea is higher with metformin immediate-release than with metformin extended release formulation 4.
• A review of metformin and the gastrointestinal tract found that metformin has a number of actions within the gut, including increasing intestinal glucose uptake and lactate production, and altering the microbiome 5.

Metformin in Older Adults

• There is no specific evidence in the provided studies regarding the use of metformin in 80-year-old females.
• However, a study on the effect of metformin on kidney function in patients with type 2 diabetes mellitus and moderate chronic kidney disease found that metformin may have an adverse effect on renal function in these patients 6.
• Another study discussed the role of metformin in the management of type 2 diabetes, including its use as a first-line agent, but did not specifically address its use in older adults 7.