From the Guidelines
Metformin remains the first-line treatment for Type 2 Diabetes (T2D) in adults without kidney disease, as it is effective in lowering blood glucose, has minimal hypoglycemia risk, and offers cardiovascular benefits. The typical starting dose is 500 mg once or twice daily with meals, gradually increasing to a target dose of 1000-2000 mg daily divided into two doses to minimize gastrointestinal side effects 1. Metformin works by decreasing hepatic glucose production, reducing intestinal glucose absorption, and improving insulin sensitivity. It is inexpensive compared to newer diabetes medications and has extensive safety data. Common side effects include diarrhea, nausea, and abdominal discomfort, which often improve with time or dose adjustment. Metformin should be temporarily held during acute illness, surgery, or procedures requiring contrast dye. For patients with an eGFR below 45 mL/min/1.73m², dose adjustment or alternative medications should be considered, and metformin is contraindicated when eGFR falls below 30 mL/min/1.73m² 1.
Some key points to consider when prescribing metformin include:
- Monitoring eGFR while taking metformin
- Reassessing the benefits and risks of continuing treatment when eGFR falls to < 45 mL/min/1.73 m²
- Temporarily discontinuing metformin at the time of or before iodinated contrast imaging procedures in patients with eGFR 30–60 mL/min/1.73 m²
- Considering SGLT2 inhibitors and GLP-1 RAs for patients with type 2 diabetes and CKD who require another drug added to metformin to attain target A1C or cannot use or tolerate metformin 1.
Overall, metformin is a well-established and effective treatment for Type 2 Diabetes, and its use should be considered in adults without kidney disease, with careful monitoring and dose adjustment as needed.
From the Research
Metformin as First-Line Treatment for Type 2 Diabetes
- Metformin is still considered the first-line treatment for Type 2 Diabetes (T2D) in adults without impaired renal function, due to its safety, low cost, and potential cardiovascular benefits 2.
- The use of metformin in patients with mild to moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-60 mL/min/1.73m2) is supported by large-scale cohort studies, which provide evidence for its safe use in these patients 2.
Alternative First-Line Therapies
- Recent studies have suggested that glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) may be considered as alternative first-line therapies for select patients with high cardiovascular risks, renal disease, or weight loss requirements 3.
- These newer agents have been shown to have cardioprotective and renoprotective benefits, and their use as monotherapy may be non-inferior or superior to metformin in certain patients 3, 4.
Considerations for Metformin Use
- Metformin remains the first-line anti-diabetic agent due to its cost-effectiveness and pleiotropic action, which produces cardiovascular benefits 4, 5.
- However, metformin-associated lactic acidosis is a hindrance to its use in patients with kidney failure, and its use in patients with severe renal impairment (eGFR < 30 mL/min/1.73m2) is generally not recommended 2, 6.
- The decision to use metformin or alternative therapies should be based on individual patient factors, including renal function, cardiovascular risk, and cost considerations 3, 5.