Biguanides are a class of oral medications derived from the French lilac plant, Galega officinalis. Now synthetically produced, they are among the most prescribed medications for managing metabolic conditions. The most widely used biguanide is metformin.
Other biguanides like phenformin and buformin were developed in the mid-20th century but were removed from the market due to safety concerns. Metformin demonstrated a more favorable safety profile and became the principal drug in its class. It is available in different formulations to suit patient needs.
How Biguanides Work
The primary action of biguanides is to reduce the amount of glucose produced and released by the liver, a process known as hepatic gluconeogenesis. By signaling the liver to slow production, biguanides help lower overall blood glucose levels.
Another way these medications work is by increasing the body’s sensitivity to insulin. This allows skeletal muscle and fat cells to more effectively absorb and use glucose from the bloodstream for energy. This action improves how existing insulin functions without increasing the body’s insulin output.
A third mechanism involves the intestines, where biguanides slightly decrease the amount of glucose absorbed from food during digestion. While this contributes to their overall effect, it is less impactful than their actions on the liver and insulin sensitivity.
Primary Medical Applications
The most common use for biguanides is managing Type 2 diabetes. Metformin is recommended as a first-line treatment because it effectively lowers blood sugar levels without causing weight gain and can reduce A1C levels by about 1%.
Beyond diabetes, biguanides are prescribed off-label for Polycystic Ovary Syndrome (PCOS). In individuals with PCOS, the medication helps lower insulin levels, which can decrease androgen and luteinizing hormone levels. This hormonal regulation can help restore more regular menstrual cycles.
Another application is managing prediabetes, where blood sugar levels are higher than normal but not yet high enough for a Type 2 diabetes diagnosis. Studies show that metformin can delay or prevent the progression from prediabetes to diabetes, especially when combined with lifestyle changes.
Common Side Effects and Safety Considerations
The most common side effects of biguanides are gastrointestinal. Up to 30% of people taking metformin experience issues like diarrhea, nausea, bloating, gas, and an upset stomach. These symptoms are most noticeable when starting the medication and tend to decrease over time. Taking the drug with meals or using an extended-release formula can minimize this discomfort.
Long-term use of biguanides can interfere with the absorption of Vitamin B12 from the intestines, leading to a deficiency over time that may cause fatigue or weakness. Regular monitoring of Vitamin B12 levels is recommended for individuals on high doses or long-term therapy.
A rare but serious risk is lactic acidosis, where lactic acid builds up in the bloodstream. This complication affects about 1 in 30,000 people taking metformin, with symptoms including muscle pain, weakness, and difficulty breathing. The risk is higher in individuals with severe kidney or liver disease, heart failure, or alcohol use disorder, which is why kidney function is assessed before starting the medication.