Metformin FDA approval history
Pro Research Analysisby 
Searched over 200M research papers
Metformin FDA Approval Timeline and Initial Restrictions
Metformin was first approved by the U.S. Food and Drug Administration (FDA) in 1994 for the treatment of type 2 diabetes mellitus. At the time of its approval, the FDA placed significant restrictions on its use due to concerns about lactic acidosis, a rare but serious complication associated with a related drug, phenformin, which had been withdrawn from the market in 1977. As a result, metformin was contraindicated in patients with heart failure and those with elevated creatinine levels, reflecting concerns about impaired drug excretion and increased risk of lactic acidosis in these populations 15.
Changes to Metformin Contraindications and Labeling
Over time, evidence accumulated that challenged the initial restrictions. In 2006, the FDA removed heart failure as a contraindication for metformin use after observational studies showed that metformin was safe and might even reduce mortality in patients with heart failure. However, the restriction for patients with elevated creatinine levels remained in place for several more years 15.
In April 2016, the FDA revised its warning regarding metformin use in patients with chronic kidney disease (CKD). The agency shifted from a serum creatinine-based definition of renal impairment to a more inclusive criterion based on estimated glomerular filtration rate (eGFR). This change allowed an estimated one million additional patients with moderate CKD (eGFR 30 to <60 mL/min/1.73 m²) to become eligible for metformin therapy, while severe CKD (eGFR <30 mL/min/1.73 m²) remained a contraindication 15.
Ongoing Safety Monitoring and Recalls
Metformin has remained the preferred initial pharmacological agent for type 2 diabetes, as recommended by the American Diabetes Association, due to its effectiveness, safety profile, and low cost . However, in recent years, the FDA has had to address new safety concerns. Between 2020 and 2022, the FDA recalled hundreds of metformin extended-release products due to the presence of N-nitrosodimethylamine (NDMA), a probable carcinogen, found at levels above the acceptable daily intake. This led to increased scrutiny and ongoing quality assessments of both immediate-release and combination metformin products 34.
New Formulations and Approvals
The FDA continues to approve new formulations of metformin to improve patient adherence and outcomes. For example, in August 2019, the FDA approved an extended-release oral suspension of metformin (Riomet ER), expanding options for patients who may have difficulty swallowing tablets .
Conclusion
Metformin’s FDA approval history reflects a balance between initial caution and evolving evidence. Since its 1994 approval, the FDA has updated metformin’s labeling and contraindications in response to new research, making the drug accessible to more patients while maintaining safety. Ongoing monitoring for impurities and new formulations ensures that metformin remains a cornerstone of type 2 diabetes management 12345.
Sources and full results
Most relevant research papers on this topic