From the Guidelines
Metformin can be used in type 1 diabetes as an adjunct therapy to insulin, particularly in overweight or obese patients with poorly controlled type 1 diabetes, as it may help reduce insulin requirements and improve metabolic control. According to the most recent and highest quality study 1, adding metformin to insulin therapy may reduce insulin requirements and improve metabolic control in patients with type 1 diabetes. The study found that metformin reduced insulin requirements by 6.6 units/day and led to small reductions in weight and total and LDL cholesterol. However, it did not improve glycemic control, with an absolute A1C reduction of 0.11%.
Key Considerations
- Metformin is typically prescribed at a starting dose of 500 mg once or twice daily, potentially increasing to 1000 mg twice daily as tolerated.
- It's used alongside insulin therapy, not as a replacement, since people with type 1 diabetes always require insulin.
- Metformin works by decreasing hepatic glucose production, improving insulin sensitivity, and reducing intestinal glucose absorption.
- Common side effects include gastrointestinal symptoms like nausea, diarrhea, and abdominal discomfort, which often improve over time.
- Metformin should be used cautiously in patients with renal impairment and is contraindicated when eGFR falls below 30 ml/min.
Clinical Implications
- While not FDA-approved specifically for type 1 diabetes, some clinicians prescribe metformin off-label when there's evidence of insulin resistance or difficulty achieving glycemic targets despite optimized insulin therapy 1.
- The use of metformin in type 1 diabetes should be individualized, taking into account the patient's specific needs and medical history.
- Clinicians should carefully weigh the potential benefits and risks of metformin therapy in patients with type 1 diabetes, particularly in terms of gastrointestinal adverse events and renal impairment.
From the FDA Drug Label
Metformin hydrochloride tablets are used with diet and exercise to help control high blood sugar (hyperglycemia) in adults with type 2 diabetes. Metformin hydrochloride tablets are not for people with type 1 diabetes. Before taking metformin hydrochloride Tablets, tell your healthcare provider if you: have type 1 diabetes. Metformin hydrochloride tablets should not be used to treat people with type 1 diabetes
Metformin should not be used in people with type 1 diabetes 2, 2.
From the Research
Metformin Use in Type 1 Diabetes
- Metformin is not licensed for use in type 1 diabetes, but it is included in some clinical guidelines as adjuvant therapy for people with type 1 diabetes who are overweight and wish to improve glycaemic control while minimising the dose of insulin 3.
- The REMOVAL study is the largest trial to date that has investigated the longer-term effects of metformin in people with type 1 diabetes 3.
- A systematic review of published clinical trials found that metformin was associated with reductions in insulin-dose requirement, HbA(1c), weight, and total cholesterol in people with type 1 diabetes 4.
- Metformin was well tolerated, albeit with a trend towards increased hypoglycaemia, but it is unclear whether the benefits of metformin are sustained beyond 1 year and whether there are benefits for cardiovascular and other key clinical outcomes 4.
Studies on Metformin
- A study published in 1999 found that metformin can decrease fasting and stimulated plasma insulin levels in patients with polycystic ovary syndrome (PCOS), but it did not examine the use of metformin in type 1 diabetes 5.
- Another study published in 1996 found that metformin does not decrease insulin resistance in PCOS, suggesting that the cellular mechanism of insulin resistance in PCOS is different from other common insulin-resistant states 6.
- A review published in 2021 discussed the use of metformin as first-line therapy for type 2 diabetes, but it did not provide information on the use of metformin in type 1 diabetes 7.