By Israel Hodish, M.D., Ph.D., co-founder and clinical research lead
Most of the 30 million patients with type 2 diabetes in the United States have used metformin during the early stages of their disease. It is an oral medication used as first-line drug for type 2 diabetes.
What is metformin?
Metformin is a synthetic modification of a molecule from the herb Galega officinalis, which has been used in Europe since the middle ages. Biguanides, the class that metformin belongs to, have been used in modern medicine since the late 1950s in Europe and since the 1990s in the US.
As far as we understand, metformin suppresses glucose production in the liver, which is a major source of glucose in type 2 diabetes. Metformin also concentrates in the intestines and may promote gut hormone secretion, which improves insulin secretion. At the time of diagnosis, most patients respond to metformin and can maintain optimal HbA1c for several years. So far the receptor, or the specific site of activity, has not been identified. This means that we have not found the exact site that the metformin molecule binds to.
Is metformin safe?
Metformin has been used safely and effectively for decades. When metformin was first prescribed in the 1950s, diabetes was an uncommon disease affecting about 1 percent of the population. Over the years, as the prevalence of diabetes has grown tenfold, we have gradually increased the number of people who use metformin, and we have developed confidence in its safety profile.
The most common side effects related to metformin are nausea and diarrhea, which usually improve over time and can be eased by using a lower dose or an extended-release formulation. Metformin can impede the absorption of vitamin B12, but this can be easily overcome with oral vitamins.
The biggest concern with any drug is the possibility of a severe or life-threatening side effect. With metformin, there is one severe side effect called lactic acidosis, but it is extremely rare and hardly seen in patients with reasonable kidney functions. Thus far, metformin has been safely used by tens of millions of people for more than a half century, and therefore we are confident prescribing it to about 10% of the population. This confidence takes time to evolve, which is why we are much more cautious with new medications.
Why do we need to add other medications for diabetes treatment?
Type 2 diabetes is a chronic condition in which insulin secretion progressively declines. Although some medications such as metformin may slow this progression, ultimately within about three years, most patients will need a second-line therapy in addition to metformin because their diabetes will progress and their HbA1c will start to rise again.
After about a decade with type 2 diabetes, most patients will become insulin deficient to the point that they will need insulin injections.
Importantly, the progression of insulin deficiency despite appropriate therapy is not a choice. It is not the patient’s fault. Rather, it is a natural course of progression with type 2 diabetes.
Metformin works for a while, longer in some than others. But eventually, other medications are added to the course of treatment, with the goal of maintaining healthy HbA1c level.