- 01Scorecard lab vs safety-check labs
HbA1c shows whether metformin is working. eGFR and vitamin B12 show whether it is still a safe fit, and a great HbA1c says nothing about either. The safety checks can fail silently: B12 drops over years with no early symptoms, and its first signs (numb or tingling feet) look like diabetic nerve damage, so only a blood test tells you where you stand.
Metformin, one of the most widely prescribed drugs for type 2 diabetes, shows up on three lines of your lab report. HbA1c (hemoglobin A1c, a 3-month average of blood sugar) tells you whether metformin is working. eGFR (estimated glomerular filtration rate, a kidney-filtering score worked out from your creatinine) tells you whether your kidneys can clear it safely. Vitamin B12 shows whether your B12 has fallen, which long-term metformin can cause. A good HbA1c says nothing about the other two.
Which lab answers which question
Each of the three labs answers a different question, and each runs on a different schedule. The table sets them side by side so you can see which result to look at for which worry.
| HbA1c | eGFR | Vitamin B12 | |
|---|---|---|---|
| Question it answers | Is metformin lowering my blood sugar? | Can my kidneys clear metformin safely? | Has my B12 fallen on long-term metformin? |
| What moves it | Your average glucose over about 3 months | Kidney function, age, dehydration, some drugs | Years of metformin use, diet, gut absorption, other causes |
| Usual cadence | At least twice a year if at goal; every 3 months after a change or if above goal 8 | Before starting and at least once a year; more often if eGFR is below 60 24 | Periodically on long-term metformin, especially with anemia or nerve symptoms 1 |
| Fasting needed? | No | No (it comes from creatinine on a basic or comprehensive metabolic panel) | No |
| Ordered automatically? | Usually, in diabetes care | Usually, as part of a metabolic panel | Often not; it is a separate order |
HbA1c measures how much of your hemoglobin (the oxygen-carrying protein in red blood cells) has sugar stuck to it, which reflects roughly the last 3 months of blood sugar. The HbA1c page and the blood sugar explainer cover how the test works; this section covers what it means on metformin.
In a pooled analysis of randomized trials, metformin used on its own lowered HbA1c by about 1.1 percentage points on average compared with placebo 6. That is an average across studies, and individual results vary. As an illustration only, someone starting at 8.2% might land somewhere around 7.1% once the effect settles. An HbA1c that has barely moved after 3 months is a result to bring to your prescriber, who will look at how the tablets are being taken, side effects, and whether the plan needs adjusting.
For reference, the ADA puts the prediabetes range at 5.7% to 6.4% and the diabetes threshold at 6.5% and above (a diagnosis needs confirmation) 9. Separate from those bands, a common treatment goal for many adults with diabetes is an HbA1c below 7%, and your prescriber may set a lower or higher goal based on your age and risk of low blood sugar 8. Compare your number with the goal your clinician gave you.
In the US, using metformin for prediabetes is off-label (not an FDA-approved use). The prediabetes page covers how metformin compared with lifestyle change in the Diabetes Prevention Program, where lifestyle change lowered risk more than metformin did.
What your A1c means in daily glucose
Your HbA1c, translated to an average glucose. Nothing leaves your browser.
Metformin taken alone rarely causes hypoglycemia (low blood sugar), because it does not push the pancreas to release insulin 1. That changes when metformin is combined with insulin or a sulfonylurea (an older class of drug that does push insulin release). If you get shaky, sweaty or confused on a combination, tell your prescriber, and treat a low as your care team has shown you. If someone has a low and cannot eat or drink safely, is confused and not improving, has a seizure or passes out, call emergency services (911 in the US). A fasting glucose result gives a single-morning snapshot; HbA1c gives the 3-month view.
Your kidneys clear metformin from the body unchanged. When kidney function falls, metformin can build up, and very high levels raise the risk of lactic acidosis, a rare but dangerous build-up of acid in the blood. For that reason the FDA ties metformin use to eGFR, a kidney score calculated from your serum creatinine, age and sex 2. eGFR is reported in mL/min/1.73 m², a standard unit adjusted for body size; you only need the number. The kidney function explainer and the eGFR page show how it is calculated.
In 2016 the FDA moved the metformin cutoff from creatinine to eGFR. The change allowed many people with mildly reduced kidney function to keep taking metformin who previously would have been told to stop 2.
Example: an eGFR of 42 against the FDA metformin cutoffsmL/min/1.73 m²
KDIGO (Kidney Disease: Improving Global Outcomes, the international kidney guideline group) gives more detailed dosing advice for clinicians than the FDA label 4. The table puts the two side by side.
| eGFR (mL/min/1.73 m²) | FDA label 2 | KDIGO 2022 guideline, for prescribers 4 | How often eGFR is checked 24 |
|---|---|---|---|
| 60 and above | Can be used | Standard dosing | At least once a year |
| 45 to 59 | Can be used | Usually same dose; monitor kidney function more closely | Every 3 to 6 months |
| 30 to 44 | Starting not recommended; reassess benefit if already taking | Guideline advises the prescriber to reduce the dose (often to half) | Every 3 to 6 months |
| Below 30 | Contraindicated (do not use) | Guideline advises discontinuing | Per kidney care plan |
These are guideline thresholds for prescribers. Dose decisions are made by your prescriber, not from this table.
A single low eGFR does not always mean lasting kidney decline; a short-term problem such as dehydration or an acute illness can sometimes pull it down for a while. Prescribers usually look at the trend across two or more results before changing metformin, the principle the trends explainer covers. If your eGFR sits below 60 on repeated tests, the chronic kidney disease page explains the stages.
Estimate your kidney filtration (eGFR)
From your creatinine. Nothing leaves your browser.
Metformin is the reason to check vitamin B12 even when you feel fine. Long-term metformin reduces how much B12 the gut absorbs, and the body's B12 stores last for years, so blood levels drift down slowly with no early symptoms 73. By the time low B12 causes trouble, the usual first sign is numbness, tingling or burning in the feet, which is also the classic sign of diabetic neuropathy (nerve damage from high blood sugar) 1. Without a B12 result, the two causes are hard to tell apart. Low B12 also has causes other than metformin, which your prescriber can look into.
Two randomized trials put numbers on the effect. In the HOME trial, a Dutch study that added metformin or placebo to insulin in people with type 2 diabetes, those who took metformin for just over 4 years had B12 levels about 19% lower than those on placebo 5. The Diabetes Prevention Program Outcomes Study (DPPOS) followed adults with prediabetes for up to 13 years. Low B12 was more common on metformin than placebo at 5 years, and each year of metformin use raised the risk of B12 deficiency by about 13% 3.
Long-term use of metformin in DPPOS was associated with biochemical B12 deficiency and anemia. Routine testing of vitamin B12 levels in metformin-treated patients should be considered.Aroda VR et al., Journal of Clinical Endocrinology and Metabolism, 2016 3
Biochemical deficiency means a low level on a blood test, whether or not symptoms have appeared. The ADA now advises periodic B12 measurement in people taking metformin long term, especially anyone with anemia or peripheral neuropathy (nerve damage in the feet and hands) 1. The guidance sets no fixed interval, so agree the cadence with your prescriber.
| Serum vitamin B12 | Category used in DPPOS 3 | What usually happens next |
|---|---|---|
| Above 298 pg/mL | Normal | No B12 follow-up needed for now; recheck on your prescriber's schedule |
| 204 to 298 pg/mL | Borderline (low-normal) | Often clarified with a methylmalonic acid (MMA) test; ask when B12 should be rechecked |
| 203 pg/mL or below | Deficient | Prescriber looks at cause and treatment, and often a full blood count for anemia |
Example: a vitamin B12 of 250 pg/mL against the DPPOS cutoffspg/mL
Labs use slightly different cutoffs (the reference ranges explainer covers why), and some report B12 in pmol/L instead of pg/mL; the lab units explainer shows how to convert. The vitamin B12 biomarker page covers what else can push the number up or down.
When serum B12 is borderline: the MMA test
Serum B12 measures B12 in the blood, which does not always match what the cells have. Methylmalonic acid (MMA) is a waste product that builds up when cells run short of B12, so a raised MMA alongside a borderline B12 points to a real shortage 7. MMA is a separate order and is often sent to a specialist outside lab, so results can take a few days. Reduced kidney function can also raise MMA, so your prescriber reads MMA alongside your eGFR, which matters for people on metformin 7.
Low B12 can also show up on a full blood count as anemia with larger-than-usual red blood cells (a high MCV, mean corpuscular volume). The CBC explainer shows where to find MCV, and the B12 deficiency page covers symptoms and causes.
Reading your follow-up results
- 1Date the HbA1cCheck when your last metformin change happened. An HbA1c drawn less than about 3 months after a change still partly reflects the old plan.
- 2Place the eGFR in its bandFind your eGFR on the FDA bands: 45 and above, 30 to 44, or below 30. Then look at the previous result; one dip is less telling than a steady decline. If you are in the 30 to 59 range, ask your prescriber whether your metformin dose should change and when eGFR should be rechecked.
- 3Look for a B12 resultIf you have taken metformin for several years and there is no B12 on your recent reports, ask whether it should be added. If B12 is borderline, ask about MMA and when to recheck.
- 4Bring the three togetherTake all three numbers, with dates, to your prescriber. Any decision about dose, stopping or a supplement is theirs to make with you.
For the bigger picture on blood sugar labs, see the blood sugar topic, and for the kidney side, the kidney topic. For a general method that works on any result, see how to read any lab result. If your prescriber recommends a B12 supplement, the vitamin B12 supplement page explains the forms and evidence. Many people on metformin also take a statin; the statins page covers those labs.
Link · US Food and Drug AdministrationFDA revises warnings on metformin in reduced kidney functionThe 2016 safety communication that set the eGFR cutoffs of 45 and 30 and the contrast-scan guidance.fda.govCitations
- American Diabetes Association Professional Practice Committee. 9. Pharmacologic approaches to glycemic treatment: Standards of Care in Diabetes 2025. Diabetes Care. 2025;48(Suppl 1):S181-S206
- US FDA. Drug Safety Communication: FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function (April 2016)
- Aroda VR et al. Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016;101:1754-1761
- Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2022;102(5S):S1-S127
- de Jager J et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ. 2010;340:c2181
- Hirst JA, Farmer AJ, Ali R, Roberts NW, Stevens RJ. Quantifying the effect of metformin treatment and dose on glycemic control. Diabetes Care. 2012;35:446-454
- NIH Office of Dietary Supplements. Vitamin B12: Fact Sheet for Health Professionals
- American Diabetes Association Professional Practice Committee. 6. Glycemic goals and hypoglycemia: Standards of Care in Diabetes 2025. Diabetes Care. 2025;48(Suppl 1)
- American Diabetes Association Professional Practice Committee. 2. Diagnosis and classification of diabetes: Standards of Care in Diabetes 2025. Diabetes Care. 2025;48(Suppl 1)
Educational context only, not medical advice or a diagnosis. Always discuss your results with a clinician.