- ACRONYMS AND DEFINITIONS
- ER - Extended-release
- IR - Immediate-release
- Met - Metformin
- P = Drugs with pediatric dosing
- METFORMIN
Metformin IR | Glucophage® | Riomet®
Dosage forms
Glucophage® tablet
- 500 mg
- 850 mg
- 1000 mg
Riomet® solution
- 500 mg/5 ml
- Comes in 120 ml and 480 ml bottle
- Comes in cherry and strawberry flavor
Dosing - Adults
Type 2 diabetes
- Starting: 500 mg twice a day or 850 mg once daily
- Maintenance: 850 - 2550 mg/day
- Max: 2550 mg/day
- Doses above 850 mg/day should be given in 2 - 3 divided doses
- Increase dose by 500 mg a week or 850 mg every two weeks
- Take with meals
Dosing - Pediatric
Type 2 diabetes (≥ 10 years old)
- Starting: 500 mg twice a day
- Max: 2000 mg/day
- Increase daily dose by 500 mg at weekly intervals
- Take with meals
Generic / Price
- Glucophage - YES/$
- Riomet - NO/$$$$ (300 ml)
Other
- Gradually increase dose to minimize gastrointestinal side effects
- Store Riomet at room temperature
- See switching between metformin IR and metformin ER for information on changing formulations
Metformin ER (Glucophage XR®)
Dosage forms
Tablet, extended-release
- 500 mg
- 750 mg
Dosing
Type 2 diabetes
- Starting: 500 mg once daily with evening meal
- Maintenance: 500 - 2000 mg/day
- Max: 2000 mg/day
- May be given in 1 - 2 divided doses
- Increase dose in increments of 500 mg at 1 week intervals
- Take with meals
Generic / Price
- YES/$Other
- Do not crush, cut, or chew tablet
- Tablet shell may be seen in stool. This is normal.
- See switching between metformin IR and metformin ER for information on changing formulations
Metformin ER (Fortamet®)
Dosage forms
Tablet, extended-release
- 500 mg
- 1000 mg
Dosing
Type 2 diabetes
- Starting: 1000 mg once daily with evening meal
- Maintenance: 1000 - 2500 mg once daily
- Max: 2500 mg once daily
- Increase dose in increments of 500 mg at 1 week intervals
- Take with evening meal. Take with full glass of water.
Generic / Price
- YES/$$-$$$ (60 tablets)Other
- Do not crush, cut, or chew tablet
- Tablet shell may be seen in stool. This is normal.
- For patients on insulin therapy, a starting dose of 500 mg is recommended
- See switching between metformin IR and metformin ER for information on changing formulations
Metformin ER (Glumetza®)
Dosage forms
Tablet, extended release
- 500 mg
- 1000 mg
Dosing
Type 2 diabetes
- Starting: 500 mg once daily with evening meal
- Maintenance: 500 - 2000 mg once daily
- Max: 2000 mg once daily
- Increase dose in increments of 500 mg at 1 - 2 week intervals
- Take with evening meal
Generic / Price
- YES/$$$$ (#60 tablets)Other
- Do not crush, cut, or chew tablet
- Tablet shell may be seen in stool. This is normal.
- See switching between metformin IR and metformin ER for information on changing formulations
- METFORMIN + DPP-4 INHIBITOR
Janumet® (sitagliptin + metformin)
Dosage forms
Tablet
- Sitagliptin - Metformin
- 50 mg - 500 mg
- 50 mg - 1000 mg
Dosing
Type 2 diabetes
- Starting: 50/500 mg twice daily with meals
- Max: 50/1000 mg twice daily with meals
- Take with meals
Generic / Price
- NO/$$$$Other
- Do not break or cut Janumet
Janumet® XR (sitagliptin + metformin ER)
Dosage forms
Tablet, extended-release
- Sitagliptin - Metformin ER
- 50 mg - 500 mg
- 50 mg - 1000 mg
- 100 mg - 1000 mg
Dosing
Type 2 diabetes
- Starting: 100/1000 mg once daily with evening meal
- Max: 100/2000 mg once daily
- Take with evening meal
Generic / Price
- NO/$$$$Other
- Do not split, crush, or chew tablets
- There have been reports of incompletely dissolved Janumet XR tablets seen in the feces. It is not known whether this material seen in feces contains active drug. If tablet is repeatedly seen in feces, assess adequacy of glycemic control.
Jentadueto® (linagliptin + metformin)
Dosage forms
Tablet
- Linagliptin - Metformin
- 2.5 mg - 500 mg
- 2.5 mg - 850 mg
- 2.5 mg - 1000 mg
Dosing
Type 2 diabetes
- Starting: 2.5/500 mg twice daily
- Max: 2.5/1000 mg twice daily
- Take with meals
Generic / Price
- NO/$$$$Jentadueto® XR (linagliptin + metformin ER)
Dosage forms
Tablet, extended-release
- Linagliptin - Metformin ER
- 2.5 mg - 1000 mg
- 5 mg - 1000 mg
Dosing
Type 2 diabetes
- Starting: 5/1000 mg once daily with a meal
- Max: 5/2000 mg once daily
- Take with a meal
Generic / Price
- NO/$$$$Other
- Do not split, chew, crush, or dissolve tablet
- Incompletely dissolved tablets have been reported with other metformin ER products. If a tablet is seen in the feces, assess adequacy of glycemic control.
Kazano® (alogliptin + metformin)
Dosage forms
Tablet
- Alogliptin - Metformin
- 12.5 mg - 500 mg
- 12.5 mg - 1000 mg
Dosing
Type 2 diabetes
- Dosing: 12.5/500 - 12.5/1000 mg twice daily
- Max: 12.5/1000 mg twice daily
- Take with food
Generic / Price
- NO/$$$$Other
- Do not split tablets
Kombiglyze™ XR (saxagliptin + metformin ER)
Dosage forms
Tablet, extended-release
- Saxagliptin - Metformin ER
- 5 mg - 500 mg
- 5 mg - 1000 mg
- 2.5 mg - 1000 mg
Dosing
Type 2 diabetes
- Starting: 5/500 mg once daily with evening meal
- Max: saxagliptin 5 mg/day; metformin 2000 mg/day
- Take with evening meal
Generic / Price
- NO/$$$$Other
- Do not crush, cut, or chew tablets
- Occasionally, the inactive ingredients of Kombiglyze XR will be eliminated in the feces as a soft, hydrated mass that may resemble the original tablet
- METFORMIN + GLITAZONE
Actoplus met® (pioglitazone + metformin)
Dosage forms
Tablet
- Pioglitazone - Metformin
- 15 mg - 500 mg
- 15 mg - 850 mg
Dosing
Type 2 diabetes
- Starting: 15/500 mg twice daily or 15/850 mg once daily
- Max: pioglitazone 45 mg/day | metformin 2550 mg/day
- Titrate to effect
- May be given in one or two divided doses
- Take with food to decrease GI upset
Generic / Price
- YES/$$Actoplus met XR® (pioglitazone + metformin ER)
Dosage forms
Tablet, extended-release
- Pioglitazone - Metformin ER
- 15 mg - 1000 mg
- 30 mg - 1000 mg
Dosing
Type 2 diabetes
- Starting: 15/1000 - 30/1000 mg once daily
- Max: pioglitazone 45 mg/day | metformin ER 2000 mg/day
- Titrate to effect
- May be given in one or two divided doses
- Take with food to decrease GI upset
Generic / Price
- NO/$$$$Other
- Swallow whole. Do not crush, cut, or chew tablet.
- Inactive ingredients may occasionally be eliminated in the feces as a soft mass that may resemble the original tablet
Avandamet® (rosiglitazone + metformin)
Dosage forms
Tablet
- Rosiglitazone - Metformin
- 2 mg - 500 mg
- 2 mg - 1000 mg
- 4 mg - 500 mg
- 4 mg - 1000 mg
Dosing
Type 2 diabetes
- Starting: 2/500 mg twice daily
- Max: rosiglitazone 8 mg/day | metformin 2000 mg/day
- Titrate to effect
- Take with food to decrease GI upset
Generic / Price
- NO/$$$$- METFORMIN + MEGLITINIDE
PrandiMet® (repaglinide + metformin)
Dosage forms
Tablet
- Repaglinide - Metformin
- 1 mg - 500 mg
- 2 mg - 500 mg
Dosing
Type 2 diabetes
- Starting: 1/500 mg twice daily with meals
- Max: repaglinide 10 mg/day; metformin 2500 mg/day
- May be given two to three times a day
- No more than 4 mg repaglinide or 1000 mg metformin should be taken per meal
- Ideally taken 15 minutes prior to a meal, but can vary from 0 - 30 minutes
Generic / Price
- YES/$$$$Other
- If meal is skipped, do not take dose
- METFORMIN + SULFONYLUREA
Glucovance® (glyburide + metformin)
Dosage forms
Tablet
- Glyburide - Metformin
- 1.25 mg - 250 mg
- 2.5 mg - 500 mg
- 5 mg - 500 mg
Dosing
Type 2 diabetes
- Starting: 1.25/250 mg once or twice daily with meals
- Max: glyburide 20 mg/day; metformin 2000 mg/day
- Increase dose in increments of 1.25/250 mg/day at intervals of 2 weeks
- Take with meals
Generic / Price
- YES/$Metaglip® (glipizide + metformin)
Dosage forms
Tablet
- Glipizide - Metformin
- 2.5 mg - 250 mg
- 2.5 mg - 500 mg
- 5 mg - 500 mg
Dosing
Type 2 diabetes
- Starting: 2.5/250 - 2.5/500 mg once or twice daily with meals
- Max: glipizide 20 mg/day; metformin 2000 mg/day
- Increase dose in increments of 2.5/250 mg/day at intervals of 2 weeks
- Take with meals
Generic / Price
- YES/$- METFORMIN + SGLT2 INHIBITOR
Invokamet® (canagliflozin + metformin)
Dosage forms
Tablet
- Canagliflozin - Metformin
- 50 mg - 500 mg
- 50 mg - 1000 mg
- 150 mg - 500 mg
- 150 mg - 1000 mg
Dosing
Type 2 diabetes
- Starting: 50/500 mg twice daily
- Maintenance: 50/500 - 150/1000 mg twice daily
- Max: 150/1000 mg twice daily
- Take with food
Generic / Price
- NO/$$$$Invokamet® XR (canagliflozin + metformin ER)
Dosage forms
Tablet, extended-release
- Canagliflozin - Metformin ER
- 50 mg - 500 mg
- 50 mg - 1000 mg
- 150 mg - 500 mg
- 150 mg - 1000 mg
Dosing
Type 2 diabetes
- Starting: 50/500 mg once daily
- Maintenance: 50/500 - 300/2000 mg once daily
- Max: 300/2000 mg once daily
- Take with morning meal
Generic / Price
- NO/$$$$Other
- Swallow tablets whole. Do not crush, cut, or chew.
Segluromet® (ertugliflozin + metformin)
Dosage forms
Tablet
- Ertugliflozin - Metformin
- 2.5 mg - 500 mg
- 2.5 mg - 1000 mg
- 7.5 mg - 500 mg
- 7.5 mg - 1000 mg
Dosing
Type 2 diabetes
- Dosing: 2.5/500 mg - 7.5/1000 mg twice a day
- Max: 7.5/1000 mg twice a day
- Individualize starting dose based on patient's current regimen
- Take with meals
Generic / Price
- NO/$$$$Synjardy® (empagliflozin + metformin)
Dosage forms
Tablet
- Empagliflozin - Metformin
- 5 mg - 500 mg
- 5 mg - 1000 mg
- 12.5 mg - 500 mg
- 12.5 mg - 1000 mg
Dosing
Type 2 diabetes
- Starting: 5/500 mg twice daily
- Maintenance: 5/500 - 12.5/1000 mg twice daily
- Max: 12.5/1000 mg twice daily
- Take with meals
Generic / Price
- NO/$$$$Synjardy® XR (empagliflozin + metformin ER)
Dosage forms
Tablet, extended-release
- Empagliflozin - Metformin ER
- 5 mg - 1000 mg
- 10 mg - 1000 mg
- 12.5 mg - 1000 mg
- 25 mg - 1000 mg
Dosing
Type 2 diabetes
- Starting: 5/1000 mg once daily
- Maintenance: 5/1000 - 25/2000 mg once daily
- Max: 25/2000 mg once daily
- Take with morning meal
Generic / Price
- NO/$$$$Other
- Swallow tablets whole. Do not crush, cut, or chew.
Xigduo™ XR (dapagliflozin + metformin ER)
Dosage forms
Tablet, extended-release
- Dapagliflozin - Metformin ER
- 5 mg - 500 mg
- 5 mg - 1000 mg
- 10 mg - 500 mg
- 10 mg - 1000 mg
Dosing
Type 2 diabetes
- Starting: 5/500 mg once daily
- Maintenance: 5/500 - 10/2000 mg once daily
- Max: 10/2000 mg once daily
- Take with food in the morning
Generic / Price
- NO/$$$$Other
- Swallow tablets whole. Do not crush, cut, or chew.
- Inactive ingredients may be eliminated in the feces as a soft, hydrated mass that may resemble the original tablet
Trijardy® XR (empagliflozin + linagliptin + metformin ER)
Dosage forms
Tablet, extended-release
- Empagliflozin - Linagliptin - Metformin ER
- 5 mg - 2.5 mg - 1000 mg
- 10 mg - 5 mg - 1000 mg
- 12.5 mg - 2.5 mg - 1000 mg
- 25 mg - 5 mg - 1000 mg
Dosing
Type 2 diabetes
- Starting:
- For patients switching from metformin with or without linagliptin, use a dosage that gives a similar total daily dose of metformin and a total daily dose of empagliflozin 10 mg and linagliptin 5 mg
- For patients switching from metformin and any regimen containing empagliflozin with or without linagliptin, use a dosage that gives a similar total daily dose of metformin, the same total daily dose of empagliflozin, and linagliptin 5 mg
- Max: Empagliflozin 25 mg/day | Linagliptin 5 mg/day | Metformin ER 2000 mg/day
- Take once daily with a meal in the morning
Generic / Price
- NO/$$$$Other
- Swallow tablets whole. Do not crush, cut, dissolve, or chew.
- Incompletely dissolved tablets may be seen in the feces. Patients should report this finding to their healthcare provider, and the provider should assess their glycemic control.
- Kidney disease dosing
- When metformin was first marketed, there was concern that it may cause lactic acidosis like phenformin, a previous biguanide (see lactic acidosis). The original prescribing information stated that it was contraindicated in patients with a serum creatinine ≥ 1.5 mg/dl in males and ≥ 1.4 mg/dl in females.
- After marketing, metformin was so widely prescribed that it was inevitably taken by many patients with kidney disease. Despite this, an increase in lactic acidosis cases was not observed.
- In 2016, the FDA loosened its recommendations on prescribing metformin in patients with kidney disease. Other professional societies have also published less stringent guidelines. Dosing guidance in renal disease from 3 organizations is detailed below.
- FDA recommendations for prescribing metformin in kidney disease
- Obtain a GFR before prescribing metformin and at least annually thereafter. Check more frequently in patients at risk for kidney disease (e.g. elderly).
- Metformin is contraindicated in patients with a GFR < 30 ml/min
- Starting metformin in patients with a GFR of 30 - 45 ml/min is not recommended
- If GFR falls to 30 - 45 ml/min in a patient taking metformin, assess the risk/benefit of continuing metformin
- Canadian Diabetes Association recommendations
- Use metformin with caution in patients with GFR 30 - 60 ml/min
- Metformin is not to be used in patients with GFR < 30 ml/min
- Australian Diabetes Society recommendations
- Use metformin with caution in patients with GFR 30 - 45 ml/min
- Metformin is not to be used in patients with GFR < 30 ml/min [16]
- Liver disease dosing
- Metformin's prescribing information states that it should be avoided in patients with clinical or laboratory evidence of liver disease because significant hepatic impairment increases the risk of lactic acidosis. Many diabetics have fatty liver disease, and metformin has been used safely in this population for years. Metformin has even been studied as a treatment for this condition.
- Patients with cirrhosis should avoid metformin. Metformin appears to be safe in patients with milder forms of liver disease. [21, 23]
- DRUG INTERACTIONS
- NOTE: The drug interactions presented here are NOT all-inclusive. Other interactions may exist. Drug interaction checkers provide the most efficient and practical way to check for interactions among multiple medications. A free interaction checker is available from Drugs.com (see Drugs.com interactions checker).
- Metformin
- Alcohol - alcohol may potentiate the effect of metformin on lactate metabolism. Patients should not drink excessively while taking metformin.
- Colesevelam (Welchol™) - colesevelam has been shown to increase levels of metformin extended-release. Monitor for side effects when combining.
- Carbonic anhydrase inhibitors - carbonic anhydrase inhibitors cause a decrease in serum bicarbonate and induce nonanion gap, hyperchloremic metabolic acidosis. This may increase the risk of lactic acidosis.
- Examples of drugs that inhibit carbonic anhydrase include:
- Topiramate (Topamax®)
- Acetazolamide (Diamox®)
- Zonisamide (Zonegran®)
- Dichlorphenamide
- Cephalexin (Keflex®) - cephalexin may increase blood levels of metformin. The significance of this interaction is unclear.
- OCT2/MATE inhibitors - metformin is an OCT2 substrate. OCT2/MATE inhibitors may increase systemic exposure to metformin thus increasing the risk for lactic acidosis.
- Metabolism and clearance
- Metformin does not undergo liver metabolism
- OCT2 - substrate
- CONVERTING BETWEEN METFORMIN IR AND METFORMIN ER
- Overview
- The maximum recommended daily dose of extended-release metformin products is lower than that of immediate-release products
- When switching from immediate-release to extended-release formulations, the dose should remain the same as long as it does not exceed the maximum recommended daily dose of the extended-release product
| Maximum daily dose for metformin formulations | |
|---|---|
| Drug | Maximum daily dose |
| Metformin IR (Glucophage®) | 2550 mg |
| Metformin ER (Glucophage XR®) | 2000 mg |
| Fortamet® | 2500 mg |
| Glumetza® | 2000 mg |
- PRICE ($) INFO
Pricing legend
- $ = 0 - $50
- $$ = $51 - $100
- $$$ = $101 - $150
- $$$$ = > $151
- Pricing based on one month of therapy at standard dosing in an adult
- Pricing based on information from GoodRX.com®
- Pricing may vary by region and availability
- BIBLIOGRAPHY
- Manufacturer's package insert
- 2 - PMID 21617112
- 3 - PMID 12651978
- 4 - PMID 11045142