A Systematic Review and Expert Evaluation of Perioperative SGLT2 Inhibitor-Associated Ketoacidosis Case Reports

The use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in the perioperative setting may lead to SGLT2i-associated postoperative ketoacidosis (SAPKA) in patients with type 2 diabetes (T2D). Therefore, cessation of this drug is recommended before surgery. We aimed to study reported cases to assess the causality of SGLT2i, identify common characteristics, potential risk factors, treatment and outcomes of SAPKA.

We conducted a systematic literature search to identify case reports of patients with metabolic acidosis and the presence of ketones who used SGLT2i in the perioperative setting. Case reports were summarised for common characteristics, assessed for quality and distributed to a panel of diabetes experts, who evaluated the likelihood of SAPKA using a questionnaire.

Ninety-three papers containing 128 case reports fulfilled the inclusion criteria. The expert panel found SAPKA to be 'likely' in 53 (41%), 'possible' in 38 (30%) and 'unlikely' in 27 (21%) cases; 10 cases (8%) could not be validated due to insufficient data or implausible timing. SAPKA was therefore considered likely or possible in 71% (91/128) of cases. Common factors identified in the SAPKA reports included a diagnosis of T2D mellitus (n = 115), impaired perioperative intake (n = 30) and insufficient insulin supplementation (n = 10). Treatment with insulin was effective, and ketoacidosis resolved in all surviving patients, although significant morbidity, including ICU admission, was reported in a substantial proportion of cases.

Confirming a SAPKA diagnosis is challenging due to the variable reporting quality and numerous confounding factors present during the perioperative period. Clinicians should remain aware of SAPKA given the increasing prevalence of SGLT2i use. Focusing on early recognition and treatment represents a potential alternative strategy to routine preoperative SGLT2i discontinuation, though this requires further prospective evaluation.

This systematic review presents an overview and discussion of the many, to date, case reports of ketoacidosis thought to be associated with perioperative SGLT2 inhibitor treatment.