Recent research published by the journal, Diabetes Care from the American Diabetes Association (ADA) concludes that metformin can help patients with both type 2 diabetes and chronic kidney disease (CKD).

What is metformin?

Metformin is one of the most prescribed drugs on the planet — and considered the 1st line of defense for patients with type 2 diabetes since the mid-90s. 

In the drug class “biguanides,” metformin has been used as a treatment option for type 2 diabetes since the late 1950s. You might also know it by the brand names Glumetza, Glucophage, Glucophage XR (extended-release), Fortamet, and Riomet. 

Metformin helps people with type 2 diabetes lower blood sugar levels in a few ways:

• Reducing the amount of glucose released by your liver
• Increasing your body’s sensitivity to insulin
• Decreasing your appetite

Unfortunately, metformin also has one of the lowest “patient adherence rates” due to the uncomfortable digestive side-effects. The first few weeks of metformin can include frequent diarrhea and gas. Always taking metformin with a meal and asking your doctor for the “extended-release” version can help these side-effects significantly. 

Metformin is also appreciated for the fact that it does not cause hypoglycemia (low blood sugars), making it a very safe option compared to more intensive treatment options.

What is chronic kidney disease?

Kidney disease — also known as nephropathy — is a very common complication of persistently high blood sugar levels in people with diabetes. Approximately 50 percent of all kidney failure cases in the United States are associated with type 2 diabetes.

Diabetes-related kidney disease is defined by damage occurring largely in the blood vessels and nerve-endings in your kidney, impairing its ability to manage and properly filter waste in your bloodstream.

There are 5 stages of kidney disease, the final stage being “end-stage renal failure” which will lead to death if a patient doesn’t receive serious intervention like a transplant or daily dialysis.

Fortunately, diligent blood sugar management can not only prevent CKD but can also prevent it from worsening after it has already developed. 

This is where metformin comes in as a potentially doubly impactful treatment option to lower blood sugar levels and protect the kidneys from further damage as seen in this most recent study.

How Metformin Prevents Kidney Disease Progression?

For patients at stage 3B or earlier in their kidney disease, metformin showed a dramatic decrease in their risk of progressing to stages 4 and 5, as well as their overall risk of dying.

The study included 10,426 patients from South Korea with both type 2 diabetes and chronic kidney disease. The patients were followed for 7.5 years.

Study Results

Patients treated with metformin:

• 13.8 percent of patients treated died during the study
• 11.4 percent progressed ESRD (end-stage renal disease)

Patients NOT treated with metformin:

• 26.8 percent of patients treated died during the study
• 24.5 percent progressed ESRD (end-stage renal disease)

The patients treated with metformin also had a 35% lower risk of all-cause mortality risk and a 33% lower risk of progressing to ESRD, after only 2.5 years of taking metformin.

“In patients with advanced CKD, if metformin is used carefully while monitoring, it could be suggested as a treatment [for type 2 diabetes] that can slow the progress of kidney disease as well as [having a] cardiovascular benefit,” said lead author Jung Pyo Lee, MD, PhD, of Seoul National University Boramae Medical Center.

Change in Best Practice Treatment?

Until now, the FDA (Food and Drug Administration) has actually cautioned against prescribing higher doses of metformin to patients with kidney disease because of a potential increase in lactic acidosis, which would further stress the kidneys.

This new research suggests that patients in the earlier stages of kidney disease could benefit from metformin without seeing an increase in lactic acid levels.

Only one participant in the entire study (with 10,426  total participants) experienced an “event” related to high levels of lactic acidosis directly related to metformin use

“The findings are reassuring that the risk of lactic acidosis is very low even in stage 4 CKD,” added the study’s authors.

“There is increasing evidence that treatment with metformin in patients with mild to moderate CKD is safe and may also confer a survival benefit,” said expert Samira Bell, MB, a consultant nephrologist at the Renal Unit of Ninewells Hospital in Dundee, UK.

“However, randomized controlled trial evidence is required before the widespread use of metformin in patients with eGFR < 30 mL/min/1.73m2 can be recommended.” 

• For those with very poor kidney function — qualified as an eGFR lower than 30 mL/min/1.73m2 — metformin should still be largely avoided.
• The research found that for patients in the later stages of kidney disease, metformin had little to no impact on the further progression of their condition.
• Given the study’s “observational” nature, experts in the USA, like Katherine R. Tuttle, MD, a professor of medicine at the University of Washington in Seattle, suggest further research is necessary before making any firm conclusions that may affect how patients are treated.

Other Issues

It’s important to note that metformin can come with unwanted side-effects that have the potential to negatively impact a patient’s health if their healthcare team isn’t aware of.

Recent 2019 research found that longterm use of metformin is linked to a deficiency in vitamin B12. The finding is particularly significant because a deficiency in B12 can lead to nerve damage completely unrelated to diabetes. 

• This means patients could develop neuropathy as a result of the medication they were taking to lower blood sugar levels and prevent diabetes complications neuropathy. 
• Low B12 levels can also lead to cognitive impairment issues and anemia.
• All patients taking metformin should have B12 levels measured routinely, suggests the research authors. Healthcare teams should consider prescribing supplemental B12 via injection to start (to bring levels up to a healthy, stable level) and then switch patients to an oral vitamin to sustain B12 levels.