The American Diabetes Association (ADA) recommends metformin monotherapy as the initial pharmacologic treatment for type 2 diabetes without contraindications.1 The ADA considers metformin safe because of its low rates of adverse effects. The main side effects of metformin include gastrointestinal intolerance from bloating, abdominal discomfort, nausea, and diarrhea.2-4
There are no reported cases of patients taking metformin under typical circumstances and experiencing hyperglycemia. Hyperglycemia is not listed by drug manufacturers as a potential adverse reaction of metformin monotherapy.2-4 However, metformin-associated hyperglycemia is a rare complication associated with overdose and the development of acute pancreatitis.5 Exact incidence of hyperglycemia associated with metformin use is difficult to estimate as its occurrence has only been found in case reports.
The first case report of a patient who developed progressive hyperglycemia was published in 2006.5 The patient intentionally overdosed on an estimated 64-85 grams of metformin, developed severe hyperglycemia, and eventually died.
A 2004 analysis examined the incidence of toxic effects in people exposed to metformin using data from the Toxic Exposure Surveillance System (TESS) database of the American Association of Poison Control Centers from 1996-2000.6 Out of 4,072 metformin-related reports, 926 involved clinical symptoms, 18 of which were hyperglycemia (0.44% of reports, 1.9% of symptomatic cases). There were nine fatalities associated with metformin, seven of which were also in patients who experienced hyperglycemia. This analysis was limited by being unable to assess the presence of preexisting diseases or comorbidities, making the relationship between metformin ingestion and the reported symptoms unclear. The authors indicated the hyperglycemia may not have been associated with metformin use as these patients may have had underlying disease states that could have contributed to the development of hyperglycemia.
Symptoms of hypoglycemia include excessive urination (polyuria), excessive thirst (polydipsia), and unexplained weight loss.7
References
- 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2024. Diabetes Care. Jan 1 2024;47(Suppl 1):S158-s178. doi:10.2337/dc24-S009
- Glucophage (metformin hydrochloride) tablets, for oral use & Glucophage XR (metformin hydrochloride) extended-release tablets, for oral use. [Package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2018.
- Riomet (metformin hydrochloride) oral solution. [Package insert]. Cranbury, NJ: Sun Pharmaceutical Industries; 2018.
- Riomet ER (metformin hydrochloride for extended-release oral suspension). [Package insert]. Cranbury, NJ: Sun Pharmaceutical Industries; 2019.
- Suchard JR, Grotsky TA. Fatal metformin overdose presenting with progressive hyperglycemia. Western Journal of Emergency Medicine. June 24, 2022 2008;9(3):160-164.
- Spiller H, Quadrani D. Toxic effects from metformin exposure. The Annals of Pharmacotherapy. 2004 May 2004;38(5)doi:10.1345/aph.1D468
- 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2024. Diabetes Care. Jan 1 2024;47(Suppl 1):S20-s42. doi:10.2337/dc24-S002
