- Jason Chu, MD
Jason Chu, MD
- Assistant Professor of Medicine
- Icahn School of Medicine at Mount Sinai
- Andrew Stolbach, MD
Andrew Stolbach, MD
- Assistant Professor, Department of Emergency Medicine
- Johns Hopkins University
- Section Editor
- Stephen J Traub, MD
Stephen J Traub, MD
- Section Editor — Toxicology
- Associate Professor of Emergency Medicine
- Mayo Medical School
- Deputy Editor
- Jonathan Grayzel, MD, FAAEM
Jonathan Grayzel, MD, FAAEM
- Senior Deputy Editor — UpToDate
- Deputy Editor — Adult and Pediatric Emergency Medicine
- Deputy Editor — Primary Care Sports Medicine (Adolescents and Adults)
- Assistant Professor of Emergency Medicine
- University of Massachusetts Medical School
In normal individuals, fasting plasma glucose levels range from about 60 to 100 mg/dL (3.3 to 5.6 mmol/L) . In patients with diabetes mellitus, insulin deficiency or insulin resistance leads to a state of hyperglycemia. Galega officinalis (goat's rue or French lilac) was used to treat diabetes in medieval Europe. The active ingredient, guanidine, was used to synthesize other antidiabetic agents in the 1920s , and the biguanide hypoglycemic agents phenformin and metformin became available for clinical use in the 1950s.
Biguanides are antihyperglycemic agents, not hypoglycemic agents; they promote euglycemia but alone are unlikely to cause hypoglycemia. Biguanides are used both as monotherapy and in combination with other oral hypoglycemic agents. They can exacerbate hypoglycemia caused by other types of antidiabetic medicines [3,4].
The major toxicity from acute or chronic biguanide use is lactic acidosis. The high rate of severe lactic acidosis from phenformin led to the withdrawal of this drug from the US market in 1976, although it remains available in several countries. Metformin is the principal biguanide in clinical use.
The management of metformin toxicity is reviewed here. A summary table to facilitate emergent management is provided (table 1). General issues relating to hypoglycemia, the therapeutic use of biguanides, and the general clinical management of drug intoxication are presented separately. (See "Physiologic response to hypoglycemia in normal subjects and patients with diabetes mellitus" and "Hypoglycemia in adults without diabetes mellitus: Diagnostic approach" and "Metformin in the treatment of adults with type 2 diabetes mellitus" and "General approach to drug poisoning in adults".)
Metformin decreases insulin resistance, decreases hepatic glucose output, and enhances peripheral glucose uptake . Proposed mechanisms of action include enhanced suppression of gluconeogenesis by insulin, reduced glucagon-stimulated gluconeogenesis, and increased uptake of glucose by muscle and adipose cells . The net effects of these changes in diabetic patients are to decrease fasting and post-prandial blood glucose by 20 to 40 percent, decrease hemoglobin A1C, decrease body weight slightly, decrease low density lipoprotein (LDL), and increase high density lipoprotein (HDL) . (See "Metformin in the treatment of adults with type 2 diabetes mellitus".)
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- Lactic acidosis
- HISTORY AND PHYSICAL EXAMINATION
- LABORATORY EVALUATION
- Studies to obtain
- Metformin concentration
- MANAGEMENT OF OVERDOSE
- Airway, breathing, circulation
- Gastrointestinal decontamination
- Sodium bicarbonate
- Extracorporeal removal
- PEDIATRIC CONSIDERATIONS
- ADDITIONAL RESOURCES
- SUMMARY AND RECOMMENDATIONS