From the Guidelines
Metformin carries a black box warning for lactic acidosis, a rare but serious metabolic complication that can occur due to metformin accumulation, particularly in patients with kidney dysfunction, as indicated in the most recent guidelines 1. Lisinopril does not have a black box warning. Crestor (rosuvastatin) also does not have a black box warning. Rybelsus (semaglutide) carries a black box warning regarding thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), observed in rodent studies, though it's unknown if this applies to humans, as noted in previous studies 1. This warning contraindicates Rybelsus in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Patients should be informed about the risk of thyroid tumors and instructed to report symptoms like a mass in the neck, difficulty swallowing, shortness of breath, or persistent hoarseness. These warnings are important safety information that helps guide appropriate medication use and monitoring, particularly in high-risk patients. For metformin, renal function should be regularly monitored, while for Rybelsus, thyroid monitoring may be warranted in certain patients. Key considerations for metformin use include its contraindication in patients with advanced renal insufficiency and the need for caution in those with impaired hepatic function or heart failure due to the increased risk of lactic acidosis, as emphasized in the latest standards of care 1. Regular monitoring for gastrointestinal side effects is also recommended for those taking metformin long-term. In contrast, lisinopril and Crestor do not have black box warnings, highlighting the importance of understanding the specific safety profiles of each medication to optimize patient care and minimize risks.
From the Research
Black Box Warnings for Metformin, Lisinopril, Crestor, and Rybelsus
- Metformin: The primary black box warning for metformin is the risk of lactic acidosis, a rare but serious complication that can occur due to accumulation of the drug in the body, particularly in patients with renal impairment 2, 3, 4, 5, 6.
- Lisinopril: There is no direct evidence of a black box warning specific to lisinopril in the provided studies. However, it is mentioned that the use of angiotensin-converting enzyme inhibitors like lisinopril can increase the risk of kidney dysfunction, particularly when used in conjunction with metformin 5.
- Crestor (Rosuvastatin): There is no evidence of a black box warning for Crestor in the provided studies.
- Rybelsus (Semaglutide): There is no evidence of a black box warning for Rybelsus in the provided studies.
Key Points Regarding Metformin-Associated Lactic Acidosis
- Metformin-associated lactic acidosis is a rare but serious complication that can occur due to accumulation of the drug in the body, particularly in patients with renal impairment 2, 3, 4, 5, 6.
- The risk of lactic acidosis is increased in patients with pre-existing renal disease, as well as in patients who experience acute kidney injury or other conditions that compromise renal function 2, 3, 4, 5, 6.
- Prolonged dialysis may be necessary to treat metformin-associated lactic acidosis, particularly in patients with severe renal impairment 5.
- Patients receiving metformin should be counseled to stop the medication and seek medical care in the event of illness or other conditions that may compromise renal function 5.