Comparing Extended-Release Metformin Products

DavidW asked

I read the explanation about the difference in release mechanisms for Glucophage XR vs Fortanet vs Glumetza. Is there any advantage or disadvantage of one to the other? How or why would a physician choose one over another? There must be some difference in actual results or effects to warrant the creation of a different mechanism? I'm a third-year medical student with pre-diabetes, and I can't seem to find this answer.

Answer

There are, unfortunately, no studies directly comparing the different extended-release metformin products in terms of their tolerability, effectiveness in reducing blood sugar or outcomes (e.g. reduction in heart attack risk, etc...)

There are, however, numerous studies that compare immediate-release metformin products to extended-release ones. Most show that extended-release products are far better tolerated in terms of the incidence of side effects like nausea, diarrhea, vomiting, etc...^[1]

In terms of which extended-release metformin is the most effective, this is difficult, if not impossible to answer due to the lack of comparative studies. Choice of the product will mostly be based on prescriber preference, patient preference, cost, and availability.

Extended-Release Metformin Products

There are 3 different extended-release metformin products, they are:

• Glucophage XR
• Fortamet
• Glumetza

All of these products release the active ingredient (metformin) slowly over time, but via different mechanisms and have slightly different pharmacokinetic profiles (e.g. rate and extent of absorption).

Glucophage XR

Glucophage XR tablets utilize a 'dual hydrophilic polymer system'.

These tablets swell when they come into contact with gastric juices and form a gel layer. Metformin is then slowly released via diffusion through this newly-formed gel matrix.

Peak drug concentrations in clinical trials are reached about 7 hours after dosing. It should be taken with food to increase overall absorption.^[2]

Fortamet

Fortamet tablets utilize 'single-composition osmotic technology (SCOT)'. Osmotic technology tablets utilize osmotic pressure to release a drug at a consistent rate over time.

The tablet has a small opening on one end where water enters, causing the drug layer in the tablet to dissolve. The entering water also increases the osmotic pressure, and the drug is pumped out the tablet opening at a constant rate.

Peak drug concentrations are reached approximately 6 hours after dosing and like Glucophage XR, it should be taken with food.^[3]

Glumetza

Glumetza tablets use gastric-retentive technology, which protects them from dissolving in the stomach. These tablets release metformin after being emptied from the stomach, in the upper gastrointestinal tract.

Peak concentrations are reached around 7 hours after dosing and are recommended to be taken after a meal for best absorption.^[4]

Choosing An Extended-Release Metformin

Extended-release metformin products are thought to have an advantage over immediate-release ones in terms of their side effect profile since the active ingredient (metformin) is released over time instead of all at once.

Not only do they have a lower incidence of nausea, diarrhea, stomach cramping and vomiting than immediate-release tablets, but studies also show that they are taken more consistently by patients (i.e. better adherence), which presumably would lead to better blood sugar control.^[5]

In terms of which extended-release metformin products is best, again, there are no comparative studies. The choice will likely depend on the:

• The dose are you taking (e.g. Glucophage XR is the only extended-release product available in a 750 mg dose. Fortamet and Glumetza are only available in doses of 500 mg and 1000 mg)
• Which is covered by your insurance (per your formulary)
• Whether or not you need a generic product (Glucophage XR and Fortamet both have generics but Glumetza does not)
• Patient preference
• Prescriber preference

We can certainly go through the clinical trials for each drug to see how they affected certain values like blood glucose and HbA1C, but picking information from trials that aren't under identical conditions is not an effective comparison.

For example, patient characteristics (e.g. gender, length of time with diabetes) doses used, how doses were adjusted, concurrent medications and length of therapy are all different in clinical trials for each extended-release drug.

In trials, all three drugs did show statistically significant decreases in fasting blood glucose, HbA1c, and body weight but, as discussed above, we can't make a definitive determination on which is 'better.'

Additional Information

It is important to remember that the FDA doesn't approve drug products (in general) based on their value or usefulness within a particular class of medication.

Perhaps the best example of this is the prescription drug Duexis, which contains famotidine and ibuprofen, both of which are available as single ingredients in over the counter products. While you can get each of those drugs for a few dollars, prescription Duexis costs over $2000 for 90 tablets.

In addition to drugs that don't seem to have much medical value and yet, are approved by the FDA, there are many 'me-too' drugs and ones with the same active ingredient but different release mechanisms simply because they can be marketed as unique drug products. Metformin products are a good example of this, as are drugs that contain amphetamines, opioids, and albuterol (e.g. Proventil, Ventolin and Proair).

Product choice in situations where there are many similar options comes down to many of the factors discussed above (e.g. cost, patient/prescriber preference).