Metformin comes in tablet and oral solution forms and in immediate-release and extended-release formulations.1-4 Manufacturers recommend taking metformin with food to avoid gastrointestinal side effects. All formulations of metformin are taken orally. Manufacturers recommend against cutting, crushing, or chewing extended-release tablets as crushing of extended-release medications can lead to loss of the controlled release which can inadvertently lead to toxicity.5
Metformin is available in strengths ranging from 500-1,000 mg.1-4 Dosages should be individualized to the patient and any up-titrations should be carefully monitored by a physician or a healthcare provider.
Immediate-release tablets and oral solution can be taken once, twice, or three times a day depending on dosage and tolerance.1-4 Manufacturers recommend dividing the dose to twice a day for dosages 850 mg and above and dividing to three times a day for dosages 2,000 mg and above. Divided doses can minimize gastrointestinal side effects.
Extended-release tablets and oral solution is recommended to be taken once a day with the evening meal.1,3,4
Oral solutions are typically administered in a marked cup or oral syringe that is issued with the prescription. The efficacy of oral solution medications depends on accurate measurement of the dosage, so it is recommended that patients use some kind of marked measuring device to ensure that they take the correct dose.6,7
Pharmacology
Metformin immediate-release tablets and oral solution reaches maximum bioavailability within 1.79-3.32 hours.1,2 Metformin extended-release tablets and oral solution reaches maximum bioavailability within 4-8 hours.1,3,
The plasma elimination half-life for all forms of metformin is approximately 6.2 hours, and the elimination half-life in blood is approximately 17.6 hours. Plasma elimination half-life is the time at which the total amount of the drug bound to plasma proteins is reduced by 50%, and blood elimination half-life is the time at which the total amount of drug bound to blood cells is reduced by 50%.8 In order to be metabolized and eliminated, metformin must be unbound from both blood and plasma.
|
Formulation
|
Tmax (h)
|
Plasma T1/2 (h)
|
Blood T1/2 (h)
|
Available Strengths (mg)
|
Maximum Dose (mg)
|
|
Immediate-release tablet
|
1.79-3.32
|
6.2
|
17.6
|
500, 850, 1,000
|
2,550
|
|
Immediate-release oral solution
|
2.2
|
6.2
|
17.6
|
500 mg/5 mL, 850 mg/8.5 mL
|
2,550
|
|
Extended-release tablet
|
4-8
|
6.2
|
17.6
|
500, 750, 1,000
|
2,000
|
|
Extended-release oral solution
|
3.5-6.5
|
6.2
|
17.6
|
500 mg/5 mL
|
2,000
|
The presence of food in the gastrointestinal tract changes the way that metformin is absorbed, however, the clinical relevance of this is unknown.1-4,9 The effect of food on absorption of metformin are outlined below:
- Immediate-release tablets: decreases absorption by 40% and delays peak absorption by 35 minutes
- Extended-release tablets: increases absorption by 50% but does not impact the speed of absorption
- Immediate-release oral solution: increases absorption by 13-16% and delays peak absorption by 1.4 hours
- Extended-release oral solution: decreases absorption by 20% and delays peak absorption by one hour
References
- Glucophage (metformin hydrochloride) tablets, for oral use & Glucophage XR (metformin hydrochloride) extended-release tablets, for oral use. [Package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2018.
- Riomet (metformin hydrochloride) oral solution. [Package insert]. Cranbury, NJ: Sun Pharmaceutical Industries; 2018.
- Riomet ER (metformin hydrochloride for extended-release oral suspension). [Package insert]. Cranbury, NJ: Sun Pharmaceutical Industries; 2019.
- Glumetza (metformin hydrochloride) extended-release tablets, for oral use. [Package insert]. Bridgewater, NJ: Valeant Pharmaceuticals; 2018.
- Nokhodchi A, Raja S, Patel P, Asare-Addo K. The role of oral controlled release matrix tablets in drug delivery systems. Bioimpacts. 2012;2(4):175-87. doi:10.5681/bi.2012.027
- Neves I, Proença L, Auxtero MD. Reproducibility and accuracy of measurement of oral liquid pharmaceutical forms, using a dosing spoon. Annals of Medicine. 2019 May 28 51(Suppl 1):86. doi:10.1080/07853890.2018.1561800
- Yin HS, Parker RM, Sanders LM, et al. Liquid Medication Errors and Dosing Tools: A Randomized Controlled Experiment. Pediatrics. Oct 2016;138(4)doi:10.1542/peds.2016-0357
- Benet LZ, Zia-Amirhosseini P. Basic principles of pharmacokinetics. Toxicol Pathol. Mar-Apr 1995;23(2):115-23. doi:10.1177/019262339502300203
- Sambol N, Brookes L, Chiang J, et al. Food intake and dosage level, but not tablet vs solution dosage form, affect the absorption of metformin HC1 in man. British Journal of Clinical Pharmacology. 1996;42(4):510-512. doi:https://doi.org/10.1111/j.1365-2125.1996.tb00017.x
