Acid-base and electrolyte disorders associated with the use of antidiabetic drugs

ABSTRACT

Introduction: The use of antidiabetic drugs is expected to substantially increase since diabetes mellitus incidence rises. Currently used antidiabetic drugs have a positive safety profile, but they are associated with certain acid-base and electrolyte abnormalities. The aim of the review is to present the current data regarding the antidiabetic drugs-associated acid-base and electrolyte abnormalities.

Areas covered: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been linked with the scarce, but serious, complication of euglycemic diabetic ketoacidosis, as well as with an increase in serum potassium, magnesium and phosphorus levels. Metformin use has been associated with the development of lactic acidosis, although many studies have doubt the direct link with this serious complication. Additionally, metformin in some studies has been linked with a decrease in serum magnesium levels. Insulin administration is associated with a reduction in serum potassium, magnesium and phosphorus concentration, along with reduced renal magnesium excretion. Pioglitazone is associated with an increase in serum magnesium levels. Current data regarding the pathophysiological mechanisms, precipitants, risk factors and presentation of the above abnormalities are discussed in the present review.

Expert opinion: Clinicians should choose appropriately between antidiabetic drugs based not only on their hypoglycemic efficacy and effects on cardiovascular risk but also based on the patient’s specific risk to develop acid-base or electrolyte derangements.

KEYWORDS:

• SGLT2 inhibitors
• metformin
• pioglitazone
• insulin
• diabetic ketoacidosis
• lactic acidosis
• electrolytes
• potassium
• magnesium
• phosphorus

Article highlights

• Metformin use has been associated with the development of lactic acidosis, although many studies have doubt the direct link with this serious complication.

• Metformin should be at least temporarily discontinued in patients who develop precipitating factors of metabolic acidosis.

• Pioglitazone is associated with a small increase in serum magnesium levels.

• Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been linked with the scarce complication of euglycemic diabetic ketoacidosis.

• SGLT2 inhibitors induce an increase in serum potassium, magnesium and phosphorus levels.

• Insulin administration is associated with a reduction in serum potassium, magnesium and phosphorus concentration.

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Declaration of interest

G Liamis has given talks and attended conferences sponsored by Bristol-Myers Squibb, Pfizer, Eli Lilly, Abbot, Amgen, Astra Zeneca, Novartis, Vianex, Teva and MSD. T Filippatos has given talks and attended conferences sponsored by Bristol-Myers Squibb, Pfizer, Eli Lilly, Abbott, Amgen, Astra Zeneca, Novartis, Vianex, Teva and MSD. M Elisaf reports personal fees from Astra Zeneca, grants and personal fees from MSD, personal fees from Pfizer, Abbott, Sanofi, Boheringer Ingelheim, Eli Lilly, GlaxoSmithKline. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.