Is metformin (biguanide) used in the treatment of type 1 diabetes mellitus (T1DM)?

Metformin in Type 1 Diabetes Mellitus

Metformin is not FDA-approved for type 1 diabetes and does not improve glycemic control (A1C), but may be considered as adjunctive therapy to insulin in overweight/obese patients with type 1 diabetes who have high insulin requirements, primarily to reduce insulin doses and body weight. 1

FDA-Approved Indication

• Metformin is explicitly NOT approved for type 1 diabetes mellitus - the FDA label clearly states "Metformin hydrochloride tablets are not for people with type 1 diabetes" 1
• Metformin is approved only for type 2 diabetes as an adjunct to diet and exercise 1

Efficacy Evidence in Type 1 Diabetes

Glycemic Control

• Metformin does NOT significantly improve A1C in type 1 diabetes - the absolute A1C reduction is only 0.11% (p=0.42), which is not clinically meaningful 2
• The 2019 ADA guidelines confirm that adding metformin to adults with type 1 diabetes caused small reductions in body weight and lipid levels but did not improve A1C 3
• The 2025 ADA guidelines reiterate that metformin was associated with small reductions in body weight, insulin dose, and lipid levels but did not sustainably improve A1C 3

Insulin Requirements

• Metformin reduces daily insulin requirements by approximately 6.6 units/day (p<0.001) when added to insulin therapy 2
• This insulin dose reduction occurs without worsening glycemic control 4, 5

Weight Effects

• Metformin produces small but significant weight reductions (approximately 3 kg) in patients with type 1 diabetes 2, 4, 5
• Weight loss is one of the primary benefits when considering metformin as adjunctive therapy 3

Lipid Effects

• Metformin provides modest improvements in lipid profiles, including reductions in total cholesterol and LDL cholesterol 2, 5

Clinical Approach When Considering Metformin

Step 1: Optimize Insulin Therapy First

• Insulin remains the essential and mainstay therapy for type 1 diabetes - this is non-negotiable 2
• Use multiple daily injections (3-4 injections/day) or continuous subcutaneous insulin infusion (pump therapy) 2
• Match insulin dosing to carbohydrate intake, premeal blood glucose, and anticipated physical activity 2

Step 2: Identify Appropriate Candidates

• Consider metformin only in overweight or obese patients with type 1 diabetes who have high insulin requirements despite optimized insulin therapy 2
• Metformin may be most beneficial in patients with poorly controlled type 1 diabetes despite optimized insulin therapy 2

Step 3: Assess for Contraindications

• Do NOT use metformin if the patient has kidney problems (eGFR <30 mL/min/1.73 m²) 3, 1
• Do NOT use in patients with diabetic ketoacidosis 1
• Avoid in patients with liver problems, congestive heart failure requiring treatment, or those who drink alcohol excessively 1

Step 4: Monitor and Adjust

• Reduce insulin doses as needed when starting metformin, particularly prandial insulin, to prevent hypoglycemia 2
• Monitor for hypoglycemia, as some studies show increased frequency of hypoglycemic events with metformin addition 4
• Assess efficacy based on changes in insulin requirements, weight, and lipid parameters rather than expecting significant A1C improvements 2
• Continue metformin only if benefits (reduced insulin requirements, weight loss, improved lipids) outweigh side effects 2

Important Safety Considerations

Lactic Acidosis Risk

• Metformin carries a rare but serious risk of lactic acidosis, particularly in patients with kidney dysfunction 1
• The risk increases with dehydration, surgery, contrast dye procedures, heart attack, severe infection, or stroke 1

Vitamin B12 Deficiency

• Long-term metformin use may be associated with vitamin B12 deficiency 3, 2
• Periodic monitoring of vitamin B12 levels should be considered, especially in patients with anemia or peripheral neuropathy 3, 2

Gastrointestinal Side Effects

• Metformin increases the risk of gastrointestinal adverse effects (bloating, abdominal discomfort, diarrhea) compared to placebo 3, 2, 5
• Taking metformin with meals helps lessen gastrointestinal side effects 1

Current Guideline Status

• The 2019 and 2025 ADA Standards of Care acknowledge that metformin has been studied in type 1 diabetes but emphasize it is not approved for this indication 3
• Metformin is recommended as the preferred initial pharmacologic agent for type 2 diabetes, NOT type 1 diabetes 3
• The evidence for adjunctive agents beyond pramlintide in type 1 diabetes continues to be evaluated through the regulatory process, but these agents (including metformin) are not approved in the context of type 1 diabetes 3

Bottom Line

Metformin should NOT be routinely used in type 1 diabetes given the lack of FDA approval and absence of meaningful A1C improvement. However, in carefully selected overweight/obese patients with type 1 diabetes who have high insulin requirements despite optimized insulin therapy, metformin may be considered off-label as adjunctive therapy to reduce insulin doses and body weight, with close monitoring for side effects and appropriate dose adjustments of insulin to prevent hypoglycemia.