Saxagliptin, metformin XR & Nutrient Depletion
Also searched as Kombiglyze. What the clinical evidence reports, what it may mean, and what to discuss with your pharmacist.
Saxagliptin, metformin XR has been associated with depletion of COENZYME Q10, FOLIC ACID, VITAMIN B12 and THIAMINE. This does not mean a deficiency will occur — it means these are worth knowing about and, if you take Saxagliptin, metformin XR long-term, worth raising with your pharmacist or healthcare provider.
Take more than one medication? Open the checker with Saxagliptin, metformin XR pre-loaded and add the rest to see overlapping nutrient signals.
Reported nutrient depletions with Saxagliptin, metformin XR
Each record below is shown as published in our licensed clinical database, with its evidence rating and citations. Expand a section for food sources and talking points.
COENZYME Q10
Insignificant DepletionANTIDIABETES DRUGS
Some antidiabetes drugs, including metformin and sulfonylureas, appear to inhibit coenzyme Q10 enzyme activity and decrease endogenous levels of coenzyme Q10. However, there is no strong evidence that coenzyme Q10 depletion is the cause of antidiabetes drug-related side effects. Furthermore, taking coenzyme Q10 does not seem to improve fasting glucose levels or glycated hemoglobin in patients with diabetes.
Coenzyme Q10 is a natural compound your cells use to produce energy, and it also acts as an antioxidant. Research shows metformin may mildly interfere with the enzyme activity your body uses to make coenzyme Q10 on its own, which can nudge levels down slightly. That said, this is rated as insignificant depletion, meaning most people on this combination do not need to worry about it or take a supplement. If you are curious whether this applies to you personally, it is worth a quick conversation with your pharmacist or doctor.
What Coenzyme Q10 (CoQ10) does & food sources
CoQ10 helps cells produce energy and acts as an antioxidant; heart and muscle tissue use it heavily.
Common food sources:
- Organ meats and fatty fish
- Whole grains
- Nuts and seeds
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
There is no routine blood test for CoQ10 in everyday practice. If you have new, unexplained muscle symptoms on a medication linked to CoQ10 (statins are the best-known example), talk to your prescriber before changing anything — symptoms have many possible causes and your prescriber has several options.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
CoQ10 is generally well tolerated, but evidence for supplementing (for example, for statin muscle symptoms) is mixed. It may also modestly affect warfarin — check with your pharmacist before combining.
Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Caution: Do not stop a prescribed medication because of this association — discuss any symptoms with your prescriber first.
Learn more about this nutrient: Coenzyme Q10 — uses, safety & interactions
References (4)
- Kishi T, Kishi H, Watanabe T, et al. Bioenergetics in clinical medicine. XI. Studies on coenzyme Q and diabetes mellitus. J Med 1976;7:307-21.
- Moradi M, Haghighatdoost F, Feizi A, Larijani B, Azadbakht L. Effect of coenzyme Q10 supplementation on diabetes biomarkers: a systematic review and meta-analysis of randomized controlled clinical trials. Arch Iran Med. 2016;19(8):588-96. doi: 0161908/AIM
- Stojanovic M, Radenkovic M. A meta-analysis of randomized and placebo-controlled clinical trials suggests that coenzyme Q10 at low dose improves glucose and HbA1c levels. Nutr Res. 2017 Feb;38:1-12. PubMed
- Suksomboon N, Poolsup N, Juanak N. Effects of coenzyme Q10 supplementation on metabolic profile in diabetes: a systematic review and meta-analysis. J Clin Pharm Ther. 2015 Aug;40(4):413-8.
FOLIC ACID
Moderate DepletionMETFORMIN (Glucophage)
Reduced levels of vitamin B12 and, to a lesser extent, folic acid occur in some people with diabetes and can contribute to hyperhomocysteinemia, adding to their already increased risk of cardiovascular disease. The reduced folate levels seen in people with diabetes have been linked to metformin use in some cases, possibly as a result of reduced folic acid absorption. Symptomatic folate deficiency is unlikely to occur with metformin, but people with diabetes may need folic acid supplements to reduce hyperhomocysteinemia. For information on foods that are rich in folate, see our chart.
Folate is a B vitamin your body uses to build healthy cells and keep homocysteine (a chemical in the blood) at safe levels. Metformin, the main workhorse in this combination, appears to interfere with how your gut absorbs folate, which can nudge levels lower over time in some people with diabetes. The rating here is moderate, meaning it is a real enough concern to keep an eye on, especially since people with diabetes can already run lower on folate and may face a higher cardiovascular risk if homocysteine climbs. It is worth asking your doctor or pharmacist whether checking your folate level or adding a supplement makes sense for you personally.
What Folic acid (folate) does & food sources
Folate is needed for cell division, red blood cell formation, and healthy fetal development.
Common food sources:
- Leafy green vegetables
- Beans, lentils, and peas
- Fortified grains and cereals
- Citrus fruits
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
Ask your provider whether folate monitoring or supplementation is appropriate for you — this matters most before and during pregnancy, and with long-term use of certain seizure or arthritis medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
Folate needs are individual. With some medications (for example, methotrexate), folic acid is often prescribed deliberately on a specific schedule — follow your prescriber's instructions rather than adding your own.
Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Caution: High-dose folic acid can mask vitamin B12 deficiency, so the two are often evaluated together.
Learn more about this nutrient: Folic Acid — uses, safety & interactions
References (5)
- Carlsen SM, Folling I, Grill V, et al. Metformin increases total homocysteine levels in non-diabetic male patients with coronary heart disease. Scand J Clin Lab Invest 1997;57:521-7.
- Carpentier JL, Bury J, Luyckx A, et al. Vitamin B12 and folic acid serum levels in diabetics under various therapeutic regimens. Diabete Metab 1976;2:187-90.
- Buysschaert M, Wallemacq PE, Dramais AS, Hermans MP. Hyperhomocysteinemia in type 2 diabetes. Diabetes Care 2000;23:1816-22.
- Aarsand AK, Carlsen SM. Folate administration reduces circulating homocysteine levels in NIDDM patients on long-term metformin treatment. J Int Med 1998;244:169-74. PubMed
- Berchtold P, Dahlqvist A, Gustafson A, Asp NG. Effects of a biguanide (metformin) on vitamin B12 and folic acid absorption and intestinal enzyme activities. Scand J Gastroenterol 1971;6:751-4.
VITAMIN B12
Moderate DepletionMETFORMIN (Glucophage)
Metformin might interfere with intrinsic factor secretion or uptake, affect bowel motility, or cause bacterial overgrowth, resulting in vitamin B12 malabsorption and hyperhomocysteinemia. There are also rare reports of megaloblastic anemia in people who have taken metformin for 5 years or more. Reduced absorption occurs in up to 30% of people taking metformin chronically and appears to be a dose-dependent effect. However, clinically significant deficiency isn't likely to develop if dietary intake of vitamin B12 is adequate, including the intake of a multivitamin or vitamin B12 supplement. The risk of deficiency is higher in those taking a higher metformin dose for 3 years or more and also in older people and vegetarians. Deficiency can be corrected with vitamin B12 supplements even if metformin is continued. Monitor for signs and symptoms of vitamin B12 and folic acid deficiency. Advise people taking metformin chronically to include adequate amounts of vitamin B12 in the diet and to have serum vitamin B12 and homocysteine levels checked annually. For information on foods that are rich in vitamin B12, see our chart.
Vitamin B12 is something your nerves and red blood cells genuinely depend on, so it is worth paying attention to here. The metformin component of this combination can interfere with how your gut absorbs B12, possibly by affecting a protein called intrinsic factor or by changing conditions in your intestines. This is rated a moderate concern, and studies suggest reduced absorption happens in a meaningful number of long-term metformin users, especially at higher doses or after several years of use. If you have been taking this medication for a while, it is a reasonable conversation to have with your pharmacist or doctor about whether checking your B12 level makes sense for you.
What Vitamin B12 does & food sources
Vitamin B12 supports red blood cell formation, nerve function, and DNA synthesis.
Common food sources:
- Meat, poultry, and fish
- Eggs and dairy products
- Fortified cereals and nutritional yeast
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
If you take an associated medication long-term, ask your healthcare provider whether checking a vitamin B12 level (sometimes with methylmalonic acid) is appropriate — especially if you notice fatigue, numbness, tingling, or memory changes.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
B12 status is easy to check and low levels are usually straightforward to address, so testing before supplementing is often the sensible order. High-dose folic acid can mask a B12 deficiency, which is one reason B12 and folate questions are best sorted out together with your provider.
Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Caution: B12 deficiency can look like other conditions — do not self-diagnose from symptoms alone.
Learn more about this nutrient: Vitamin B12 — uses, safety & interactions
References (12)
- Carlsen SM, Folling I, Grill V, et al. Metformin increases total homocysteine levels in non-diabetic male patients with coronary heart disease. Scand J Clin Lab Invest 1997;57:521-7.
- Carpentier JL, Bury J, Luyckx A, et al. Vitamin B12 and folic acid serum levels in diabetics under various therapeutic regimens. Diabete Metab 1976;2:187-90.
- Zapletal C, Heyne S, Golling M, et al. Influence of selenium therapy on liver microcirculation after warm ischemia/reperfusion: an intravital microscopy study. Transplant Proc 2001;33:974-5. PubMed
- Gilligan MA. Metformin and vitamin B12 deficiency (letter). Arch Intern Med 2002;162:484-5. PubMed
- Kim J, Ahn CW, Fang S, Lee HS, Park JS. Association between metformin dose and vitamin B12 deficiency in patients with type 2 diabetes. Medicine (Baltimore). 2019 Nov;98(46):e17918. PubMed
- Kamrul-Hasan AB, Alam MS, Chanda PK, Selim S. Serum Vitamin B12 Levels in Patients with Type 2 Diabetes Mellitus on Metformin Compared to those Never on Metformin: A Cross-sectional Study from Bangladesh. Mymensingh Med J 2021;30(4):913-920.
- Al-Fawaeir S, Al-Odat I. Influence of metformin intake on serum vitamin B12 levels in patients with type 2 diabetes mellitus. PLoS One 2022;17(12):e0279740. PubMed
- Callaghan TS, Hadden DR, Tomkin GH. Megaloblastic anemia due to vitamin B12 malabsorption associated with longterm metformin treatment. Br Med J 1980;280:1214-5.
- Andres E, Noel E, Goichot B. Metformin-associated vitamin B12 deficiency (letter). Arch Intern Med 2002;162:2251-2. PubMed
- Bauman WA, Spungen AM, Shaw S, et al. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care 2000;23:1227-31. PubMed
- Bauman WA, Shaw S, Jayatilleke E, et al. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care 2000;23:1227-31. PubMed
- Ting RZ, Szeto CC, Chan MH, et al. Risk factors of vitamin B12 deficiency in patients receiving metformin. Arch Intern Med 2006;166:1975-9. DOI
THIAMINE
Insufficient EvidenceMETFORMIN (Glucophage)
Thiamine is involved in the entrance of glycolytic pyruvate into the mitochondrial Kreb's cycle. Reducing thiamine activity might lead to increased amounts of pyruvate being converted to lactic acid. This effect might be responsible for some of the cases of lactic acidosis associated with metformin. This theoretical effect is based on preclinical animal research with phenformin, a similar drug that was produced prior to metformin. This has not yet been substantiated in humans or with the use of metformin.
Thiamine is a B vitamin your body needs to properly convert food into usable energy, particularly inside your cells' energy centers. Some animal research with older diabetes drugs in the same family as metformin hinted that metformin might interfere with how thiamine works in that energy process, but this has never been confirmed in humans taking metformin itself. The evidence here is genuinely insufficient, so there is no reason to worry right now. That said, if you are curious or have symptoms like unusual fatigue, it is always worth a conversation with your pharmacist or doctor.
What Vitamin B1 (thiamine) does & food sources
Thiamine helps convert food into energy and is essential for nerve and heart function.
Common food sources:
- Whole grains and fortified cereals
- Pork
- Beans and lentils
- Nuts and seeds
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
Ask about thiamine if you take an associated medication (for example, a long-term loop diuretic in heart failure) and have symptoms like fatigue or worsening heart failure control — this is an area your care team can weigh.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
Thiamine is water-soluble and generally low-risk, but supplementing to treat a suspected problem should still be clinician-guided so the real cause is not missed.
Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Learn more about this nutrient: Thiamine — uses, safety & interactions
This tool is educational and is not a substitute for professional medical advice. An association is not a diagnosis and does not mean a deficiency will occur. Always talk to your pharmacist or healthcare provider before starting, stopping, or changing any medication or supplement.
Disclaimer: This checker finds which nutrients might be depleted by prescription or over-the-counter medications. Each nutrient depletion issue is rated based on clinical significance. Use your own professional judgment prior to making clinical decisions.© 2026 Therapeutic Research Center Licensed records refresh weekly · last updated July 3, 2026.
More about Saxagliptin, metformin XR
What drug-induced nutrient depletion means
Some medications can, over time, lower the levels of certain vitamins, minerals, or other nutrients — through reduced absorption, increased loss, or changes in how the body uses them.
Association is not deficiency
An entry here means a depletion has been reported or studied — not that it happens to everyone, or that you are deficient. Dose, duration, diet, and your own health all matter.
Evidence varies by pair
Some drug–nutrient links (like metformin and vitamin B12) are well studied; others rest on limited or preliminary research. Each entry shows the evidence rating from our licensed clinical database.
When to ask about labs
If you take an associated medication long-term, ask your healthcare provider whether monitoring is appropriate for you. Not everyone needs testing — your provider can weigh your dose, duration, and symptoms.
Don't self-supplement blindly
Supplements are not risk-free: some can interact with medications, and some (like potassium or magnesium) can be risky with kidney disease. Talk to your pharmacist before adding anything.
Never stop a medication over this
These medications are prescribed for good reasons, and the benefit usually far outweighs a manageable nutrient consideration. Any change belongs in a conversation with your prescriber.
Food first, usually
For many nutrients, a varied diet covers the gap. Each entry lists common food sources; a supplement is a decision to make with your pharmacist or provider, not a default.
Saxagliptin, metformin XR & nutrients: FAQs
Does Saxagliptin, metformin XR deplete COENZYME Q10?
Should I take a supplement because I take Saxagliptin, metformin XR?
Should I stop taking Saxagliptin, metformin XR?
Where does this information come from?
Questions about Saxagliptin, metformin XR and your nutrition?
Ask a licensed pharmacist — free, no appointment needed.
Sources & How We Checked
Nutrient depletion records for Saxagliptin, metformin XR are evidence-graded and sourced from the Natural Medicines database, and are displayed as published with their citations.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for drug-induced nutrient depletions, supplements, and interactions — the basis for this page.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for medication overviews across the site.
Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.