What is the difference between Glucophage®, Fortamet® and Glumetza®?

Fortamet® and Glumetza® are available as generics, but the actual difference in tolerability may not outweigh the financial burden to patients. While there is limited difference in tolerability and effectiveness, there is a whopping difference in cost.

Metformin is notorious for causing GI discomfort. It is available as Glucophage®, Glumetza® and Fortamet®. You may hear that Fortamet® and Glumetza® are tolerated better due to a difference in drug release. Glumetza® is slowly released in the duodenum, while Fortamet® is released as dissolved drug via a pin-sized hole through a semi-permeable membrane.1

The tolerability of all metformin formulations can be improved when taken with a full meal, not just a snack. The actual variability in GI side effects between extended-release formulations is minimal.2 Patient cost may be significantly different between each formulation. Thirty tablets of metformin ER (generic Glucophage® XR) are about $20 compared to $270 for generic Fortamet® and $1,660 for generic Glumetza®. There is no significant difference in HbA1c control between each formulation when similar doses are used.2

Recommend patients start with generic metformin ER and advise them that the medication should be taken with food. If GI symptoms are intolerable, consider splitting the dose two to three times a day with meals. If symptoms are still intolerable, recommend generic Fortamet® or Glumetza® as a second line option but remind patients and providers of the significant difference in cost.

Refer to the summary handout provided for more information on cost.

Metformin Formulation

Duration of Action

Key Points

Average Wholesale Price

Metformin Immediate Release (IR)

8-12 hours

  • GI Discomfort

500mg tablet
1000mg tablet


Metformin Extended Release (ER)

24 hours

  • Better tolerability than IR

500mg tablet
750mg tablet



24 hours

  • Slow Release of drug to duodenum while tablet remains in stomach
  • Must be taken with high fat, full meal for max absorption

Brand 500mg
Brand 1,000mg


Generic 500mg
Generic 1000mg



24 hours

  • Water is absorbed through semi-permeable membrane and dissolved drug is released through a pin-sized hole
  • Tablet 'membrane' or coating is excreted unchanged (patients may see whole tablet shell in stool)

Brand 500mg
Brand 1,000mg


Generic 500mg
Generic 1,000mg