Weakness is reported on the metformin label, but that does not establish the cause or urgency of a new symptom. Two things on the same label make the question worth reading carefully: unusual sleepiness is one of the early signs of lactic acidosis, and long-term use can lower vitamin B12 [1]. Metformin is approved to improve blood sugar in type 2 diabetes; any other use is off-label.
Weakness was reported by 9% on metformin vs 6% on placebo
That figure comes from a clinical trial of metformin tablets that the label summarizes, with 141 people on metformin and 145 on placebo [1]. Weakness, which the label calls asthenia, was a little more common on the drug. So was headache.
| Effect | Metformin | Placebo | Where on the label |
|---|---|---|---|
| Weakness (asthenia), immediate-release | 9% | 6% | Table 1 |
| Headache, immediate-release | 6% | 5% | Table 1 |
| Lightheadedness, immediate-release | 1% to 5% | Less often | Section 6.1 list |
| Dizziness and headache, extended-release | 1% to 5% each | Less often | Section 6.1 list |
| Low blood sugar | 1% to 5% (immediate-release); higher with insulin or a sulfonylurea | Less often | Section 6.1; warning 5.3 |
| New low vitamin B12 | About 7% in 29-week trials | Not given | Warning 5.2 |
Metformin hydrochloride tablets and extended-release tablets prescribing information, September 2026 version.
Why metformin can make you tired
The label lists weakness as an adverse reaction without establishing one cause. It separately warns about vitamin B12 reductions, lactic acidosis and low blood sugar with insulin or a sulfonylurea [1].
Stomach side effects are the most common by far. In the same trial, diarrhea affected 53% on metformin vs 12% on placebo, and nausea or vomiting 26% vs 8% [1]. Those rates do not establish that stomach upset caused a particular episode of weakness. Persistent symptoms and fluid loss need clinical assessment rather than assuming they explain the fatigue.
Metformin can lower vitamin B12 over the long term
About 7% of people with previously normal levels developed low vitamin B12 in 29-week trials, according to the label. It says the drop "may be associated with anemia but appears to be rapidly reversible" with stopping metformin or taking B12 [1].
Longer data come from the Diabetes Prevention Program Outcomes Study, funded by the National Institutes of Health, which followed people for up to 13 years [2]. Low or borderline-low B12 was found in 19.1% on metformin vs 9.5% on placebo at 5 years, and 20.3% vs 15.6% at 13 years. Each year of use was associated with about 13% higher odds of B12 deficiency, an association rather than proof that every extra year has that effect for every person. The comparison began as randomized treatment, followed by open-label metformin; it was not 13 years of continuously blinded placebo-controlled treatment.
| Measure | Metformin | Placebo | When |
|---|---|---|---|
| Low B12 (203 pg/mL or less) | 4.3% | 2.3% | 5 years |
| Low B12 (203 pg/mL or less) | 7.4% | 5.4% | 13 years (difference not significant) |
| Low or borderline-low B12 (298 pg/mL or less) | 19.1% | 9.5% | 5 years |
| Low or borderline-low B12 (298 pg/mL or less) | 20.3% | 15.6% | 13 years |
Aroda 2016, Journal of Clinical Endocrinology and Metabolism; NIH-funded.
The study found anemia more common on metformin, though not linked to B12 status, and nerve problems (neuropathy) more common in metformin users with low B12 [2]. The label's monitoring rule is direct: "Measure hematologic parameters on an annual basis and vitamin B12 at 2 to 3 year intervals" [1]. If you've been on metformin for years and feel run down, ask whether your B12 and blood count are due.
When sleepiness is a warning sign
Unusual sleepiness can be one warning symptom of lactic acidosis; muscle pain, trouble breathing and stomach symptoms are others. You do not need every symptom to seek help. It's the subject of metformin's boxed warning, which says its onset "is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain" [1]. It is rare, but it has caused deaths.
| Pattern | Possible cause per the label | What to do |
|---|---|---|
| New or persistent weakness | Weakness is reported, but timing alone does not establish the cause | Tell your prescriber; very marked weakness or unusual sleepiness follows the urgent Medication Guide warning |
| Fatigue during long-term use | Low B12 or anemia may need assessment; symptoms alone do not diagnose either | Ask the clinician whether blood count and B12 testing are due |
| Shaky, sweaty or confused, if you also take insulin or a sulfonylurea | Low blood sugar | Follow your low-blood-sugar plan; tell your prescriber |
| Unusual sleepiness, marked weakness, muscle pain, trouble breathing, stomach pain or feeling cold | Lactic acidosis (rare) | Stop and get medical help right away, as the Medication Guide says |
The label lists what raises the risk of lactic acidosis: kidney problems, some drugs such as topiramate, age 65 or older, contrast imaging tests, surgery and other procedures, low-oxygen states such as acute heart failure, heavy drinking, liver problems and mitochondrial diseases [1]. Dehydration from fever, vomiting or diarrhea is on the Medication Guide's list too.
Headache was reported by 6% vs 5% on placebo
That's a small difference [1]. Headache is also one of the classic signs of low blood sugar, which matters mainly if you take insulin or a sulfonylurea alongside metformin. The label says metformin "may increase the risk of hypoglycemia when combined with insulin and/or an insulin secretagogue" [1].
Insomnia isn't listed on the metformin label
A search of the current label finds no mention of insomnia [1]. If you're sleeping badly since starting it, tell your prescriber, but absence from the label cannot establish whether metformin caused an individual sleep change.
Does metformin tiredness go away?
The label doesn't say how long weakness lasts. It does show that extended-release tablets had lower stomach side effect rates in their trials: diarrhea in 10% vs 3% on placebo, against 53% vs 12% for immediate-release [1]. Those were different trials, so the numbers aren't a direct comparison. Whether a different form or schedule suits you is your prescriber's call.
Taking metformin for longevity doesn't change the label's risks
Metformin for aging is off-label, and people taking it that way face the same label risks, including the B12 effect over years. The evidence for that use is covered in metformin for longevity. How people get a prescription is in getting metformin prescribed online, and how it compares with a GLP-1 is in metformin vs Ozempic. If you're on a GLP-1 instead, see does Wegovy make you tired.