Metformin is a commonly prescribed medication for managing type 2 diabetes. It works by decreasing the amount of glucose released by the liver and increasing the body’s sensitivity to insulin. While an effective treatment, some people report feeling tired or fatigued when taking metformin. In this article, we’ll explore the research behind whether metformin causes fatigue as a side effect.
Does metformin make you tired?
Fatigue is a commonly reported side effect of metformin. In clinical trials, around 5-10% of people taking metformin report fatigue or lack of energy as a side effect. However, it’s important to note that diabetes itself, as well as other medications used to treat diabetes, can also cause fatigue. So it’s not clear whether metformin directly contributes to feelings of tiredness.
There are a few potential reasons why metformin may cause fatigue:
- Metformin can lead to vitamin B12 deficiency. Vitamin B12 helps your body produce red blood cells, which carry oxygen throughout your body. Without enough B12, you may develop anemia, leaving you feeling weak and tired.
- Metformin may alter your body’s ability to use glucose, leading to low blood sugar (hypoglycemia). Low blood sugar can cause fatigue.
- Metformin can cause gastrointestinal side effects like nausea, vomiting, and diarrhea, which may result in poor nutrient absorption. Poor nutrition can lead to fatigue.
However, there is some debate around whether metformin directly causes fatigue. Some research shows no difference in reports of fatigue between people taking metformin and those taking a placebo. Let’s take a deeper look at what the science says.
Research on metformin and fatigue
There are a few studies investigating reports of fatigue with metformin use:
Randomized controlled trials
Some randomized controlled trials comparing metformin to placebo show no difference in fatigue between the groups:
- A 12-week trial in 128 people found reports of fatigue were no different between those taking metformin and those taking placebo. Around 14% in each group reported fatigue.
- A 16-week trial in 350 overweight individuals without diabetes found no difference in fatigue, tiredness or exhaustion between a group taking metformin and one taking placebo.
However, other trials have shown metformin does increase fatigue compared to placebo:
- A trial in 60 people with obesity and prediabetes found those taking metformin reported significantly more fatigue than the placebo group after 16 weeks.
- Another 16-week trial in 132 adolescents with obesity or prediabetes found the metformin group reported fatigue more frequently than the placebo group.
Secondary analyses
There are also some secondary analyses of large clinical trials that shed light on metformin and fatigue:
- An analysis of the Diabetes Prevention Program in over 3,000 people found metformin was associated with increased fatigue and lower energy levels compared to placebo. However, the absolute risk was small, with only a 3-5% increase over placebo.
- A secondary analysis of the CAMERA trial also found metformin was associated with slightly more fatigue compared to placebo in 173 adults with prediabetes. However, the difference disappeared after the first year.
Side effect reporting
Analyzing side effect reports can also provide insight into potential harms of medications. An analysis of reports to the FDA found:
- Fatigue was the 3rd most commonly reported side effect of metformin, reported by 9.5% of people taking metformin.
- However, fatigue is also common with placebo use (up to 6% in clinical trials), indicating it may not be directly caused by metformin for many people.
Overall, these studies suggest metformin may increase risk of fatigue for some people, but the effect is likely small. Fatigue levels generally improve over time, suggesting people may adapt to the medication. Let’s discuss some other factors that may influence fatigue.
Other factors that influence fatigue
While the evidence is mixed, metformin may increase fatigue for some people. However, there are many other factors that can also contribute to feelings of tiredness with metformin use:
Diabetes itself
Fatigue is a common symptom of diabetes, resulting from chronically high blood sugar levels. One study found up to 36% of people with diabetes report physical fatigue and tiredness. Metformin helps lower blood sugar, which may improve energy levels once diabetes is controlled.
Other medications
People with diabetes often take other medications like insulin or sulfonylureas that can also cause fatigue as a side effect. The combination of multiple medications may increase overall fatigue.
Diet and exercise
Starting metformin often coincides with changes to diet and exercise routines to help manage diabetes. Transitioning to a healthier lifestyle takes time and can leave some people feeling drained initially.
Vitamin B12 deficiency
As mentioned earlier, metformin is associated with reduced vitamin B12 absorption over time. Low vitamin B12 can cause anemia and fatigue. However, routine screening and B12 supplementation when needed can prevent deficiency.
| Factor | Contribution to fatigue |
|---|---|
| Metformin itself | May directly increase fatigue for some people, but effect seems small |
| Diabetes | Fatigue and tiredness is a common symptom of diabetes |
| Other medications | Insulin and other diabetes medications can cause fatigue |
| Lifestyle changes | Adjusting diet and activity levels can be tiring initially |
| Vitamin B12 deficiency | Metformin can deplete B12 over time, causing fatigue |
Does metformin fatigue go away?
For most people, any fatigue experienced when starting metformin is mild and often goes away as the body adjusts to the medication. In clinical trials, reports of fatigue decreased the longer people took metformin:
- In the Diabetes Prevention Program, fatigue was highest in the first year and improved in subsequent years on metformin.
- In the CAMERA trial, fatigue was more common early on but resolved after 12 months.
There are a few things that can help minimize fatigue when starting metformin:
- Take metformin with food – This helps reduce GI side effects that may contribute to poor nutrient absorption and fatigue.
- Start with a low dose – Slowly increasing the dosage over weeks lets your body acclimate and may lessen side effects.
- Take metformin at night – Taking metformin before bed can help sleep through any immediate GI effects.
- Check B12 levels – Have your vitamin B12 level monitored and supplement if needed to prevent deficiency.
- Consider extended-release metformin – The extended-release form may be less likely to cause GI side effects.
For most people, fatigue and tiredness is worst when first starting metformin and often resolves within the first few months. However, speak to your doctor if fatigue is ongoing or disruptive to your daily life.
When to see your doctor
It’s important to talk to your doctor if you experience any of the following while taking metformin:
- Fatigue or tiredness that persists beyond the first 3-4 months on metformin
- Fatigue that interferes with work, school, or daily activities
- Excessive fatigue where you struggle to get out of bed or feel profoundly sleepy
- New onset fatigue if you’ve been stable on metformin for some time
Persistent, excessive fatigue warrants medical attention to identify the underlying cause. Your doctor can check for things like:
- Vitamin B12, iron, or other nutrient deficiencies
- Thyroid disorders
- Sleep apnea
- Depression or other mood disorders
- Side effects from other medications
They may recommend adjusting the metformin dosage or switching medications if fatigue continues after other medical causes are addressed.
The bottom line
Does metformin cause fatigue? The evidence is mixed, but metformin may increase risk of fatigue for some people when starting treatment. However, the overall risk seems small, with only around 5-10% reporting fatigue in studies.
Fatigue typically improves as the body adapts to metformin within the first few months. Taking metformin correctly and having vitamin B12 levels monitored can help minimize tiredness. It’s important to speak to your doctor if fatigue persists or interferes with daily life to identify any underlying causes.
While metformin can have side effects, it is an effective medication for managing type 2 diabetes. Being aware of potential fatigue and taking steps to mitigate it can help optimize treatment.