What are the differences between Glucophage (Metformin) ER and regular Glucophage (Metformin) in terms of efficacy and dosing for patients with type 2 diabetes?

From the Guidelines

Glucophage ER and regular Glucophage are equally effective in controlling blood glucose levels in type 2 diabetes patients, but the extended-release formulation may offer improved tolerability and reduced gastrointestinal side effects. The primary difference between the two formulations lies in their release mechanisms, which affects dosing frequency and side effect profiles. Regular Metformin is typically taken 2-3 times daily with meals, while Metformin ER (Extended Release) is usually taken once daily with the evening meal. Both formulations have the same maximum daily dose of 2000-2500mg and work by decreasing hepatic glucose production, reducing intestinal glucose absorption, and improving insulin sensitivity 1.

The extended-release formulation gradually releases medication throughout the day, which can reduce gastrointestinal side effects like nausea, diarrhea, and abdominal discomfort that are common with regular Metformin. This improved tolerability may enhance medication adherence. For patients new to Metformin, starting with a low dose (500mg) and gradually increasing can minimize side effects with either formulation. Patients with renal impairment require dose adjustments for both formulations. The extended-release version may be particularly beneficial for patients with compliance issues or those experiencing significant gastrointestinal side effects on regular Metformin.

Key considerations in choosing between Glucophage ER and regular Glucophage include:

• Efficacy: Both formulations are equally effective in controlling blood glucose levels.
• Tolerability: The extended-release formulation may offer improved tolerability and reduced gastrointestinal side effects.
• Dosing frequency: Regular Metformin is taken 2-3 times daily, while Metformin ER is taken once daily.
• Renal impairment: Patients with renal impairment require dose adjustments for both formulations.
• Compliance: The extended-release version may be beneficial for patients with compliance issues.

According to the most recent and highest quality study, Metformin is the preferred initial pharmacologic agent for the treatment of type 2 diabetes, and it is available in an immediate-release form for twice-daily dosing or as an extended-release form that can be given once daily 1. The principal side effects of metformin are gastrointestinal intolerance due to bloating, abdominal discomfort, and diarrhea; these can be mitigated by gradual dose titration. The drug is cleared by renal filtration, and very high circulating levels have been associated with lactic acidosis, although this complication is very rare.

In terms of specific recommendations, the American Diabetes Association recommends a patient-centered approach to choosing appropriate pharmacologic treatment of blood glucose, considering factors such as comorbidities, hypoglycemia risk, effects on body weight, side effects, cost, and patient preferences 1. Metformin is effective and safe, is inexpensive, and may reduce the risk of cardiovascular events and death.

Overall, the choice between Glucophage ER and regular Glucophage should be based on individual patient needs and preferences, taking into account factors such as tolerability, dosing frequency, and renal impairment. The extended-release formulation may offer improved tolerability and reduced gastrointestinal side effects, making it a suitable option for patients with compliance issues or those experiencing significant gastrointestinal side effects on regular Metformin.

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 A 24-week, double-blind, randomized study of metformin hydrochloride extended-release tablets, taken once daily, 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: 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

The answer to whether Glucophage ER gives better control than regular Glucophage is that there is no significant difference in terms of efficacy between the two formulations, as the extent of absorption (as measured by AUC) is comparable.

• Key points:
  • The peak plasma levels are approximately 20% lower for Glucophage ER compared to regular Glucophage.
  • The extent of absorption (as measured by AUC) is similar between Glucophage ER and regular Glucophage.
  • A 24-week study showed similar changes in HbA1c and Fasting Plasma Glucose between Glucophage ER and regular Glucophage 2. The dosage of Glucophage ER is once daily, while regular Glucophage is typically taken twice daily. In summary, Glucophage ER and regular Glucophage have similar efficacy, but the ER formulation offers the convenience of once-daily dosing. 2 2

From the Research

Efficacy of Glucophage ER vs Regular Glucophage

• The efficacy of Glucophage ER (Metformin ER) and regular Glucophage (Metformin) in controlling blood sugar levels in patients with type 2 diabetes has been compared in several studies 3, 4, 5.
• A study published in 2005 found that patients with type 2 diabetes who were switched from regular Glucophage to Glucophage ER achieved comparable glycemic control when the total daily dose was the same 3.
• Another study published in 2017 found that Metformin ER was as effective as Metformin IR in maintaining glycemic control at equivalent doses, and that the side effect profile was better for Metformin ER 4.
• A review of the literature published in 2015 found that Metformin is the first-line treatment for type 2 diabetes, and that other glucose-lowering drugs should be chosen based on their adverse effect profiles 6.

Dosing and Tolerability

• Glucophage ER allows for once-daily dosing, which can improve patient adherence and tolerability compared to regular Glucophage, which is typically taken twice or three times a day 7, 5.
• A study published in 2004 found that patients who were switched from regular Glucophage to Glucophage ER experienced fewer gastrointestinal side effects, such as diarrhea and nausea 7.
• Another study published in 2011 found that extended-release metformin improved gastrointestinal tolerability and allowed for once-daily dosing, making it a convenient option for patients with type 2 diabetes 5.

Side Effect Profile

• The side effect profile of Glucophage ER and regular Glucophage has been compared in several studies, with Glucophage ER generally having a better tolerability profile 7, 4, 5.
• A study published in 2017 found that the incidence of side effects, such as diarrhea, dyspepsia, and flatulence, was lower with Metformin ER compared to Metformin IR 4.
• Another study published in 2004 found that patients who were switched from regular Glucophage to Glucophage ER experienced a significant reduction in gastrointestinal side effects 7.