Bruce R. Leslie, MD, MSPH; Leslie E. Gerwin, JD, MPH, MPA; Simeon I. Taylor, MD, PhD
Acknowledgment: The authors thank Dr. Viktor Jörgens for drawing their attention to and translating a portion of the writings of Josef Freiherr von Mering.
Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-1463.
Corresponding Author: Bruce R. Leslie, MD, MSPH, Seventh Doctor Consulting, 213 Carnegie Center #3023, Princeton, NJ 08543; e-mail, email@example.com.
Current Author Addresses: Dr. Leslie: Seventh Doctor Consulting, 213 Carnegie Center #3023, Princeton, NJ 08543.
Prof. Gerwin: Program in Law and Public Affairs, Princeton University, 343 Wallace Hall, Princeton, NJ 08544.
Dr. Taylor: University of Maryland School of Medicine, MSTF 357-B, 655 West Baltimore Street, Baltimore, MD 21201.
Author Contributions: Conception and design: B.R. Leslie, L.E. Gerwin.
Analysis and interpretation of the data: B.R. Leslie, L.E. Gerwin.
Drafting of the article: B.R. Leslie, L.E. Gerwin.
Critical revision of the article for important intellectual content: B.R. Leslie, L.E. Gerwin.
Final approval of the article: B.R. Leslie, L.E. Gerwin, S.I. Taylor.
Collection and assembly of data: B.R. Leslie.
On 15 May 2015, the U.S. Food and Drug Administration (FDA) warned that administration of sodium–glucose cotransporter-2 (SGLT2) inhibitors could lead to ketoacidosis in patients with diabetes mellitus. This announcement came more than 2 years after the FDA's first approval of an SGLT2 inhibitor, although the phenomenon had been known for more than 125 years. Luminaries of diabetes research (including Josef von Mering, Frederick Allen, I. Arthur Mirsky, and George Cahill) had described ketosis and ketoacidosis induced by administration of the phytochemical phlorizin, the prototypical SGLT inhibitor, as well as in patients with familial renal glucosuria, a condition that is considered a natural model of SGLT2 inhibition. Neither government regulators nor manufacturers of SGLT2 inhibitors evinced an awareness of this extensive historical record. The absence of historical inquiry delayed notice of ketoacidosis as an adverse reaction, which could have reduced the burden of illness from these drugs.
Leslie BR, Gerwin LE, Taylor SI. Sodium–Glucose Cotransporter-2 Inhibitors: Lack of a Complete History Delays Diagnosis. Ann Intern Med. 2019;171:421–426. doi: 10.7326/M19-1463
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Published: Ann Intern Med. 2019;171(6):421-426.
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