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Sulfonylurea-related hypoglycemia may lead to negative cardiac effects
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In adults with type 2 diabetes treated with a sulfonylurea, asymptomatic hypoglycemic episodes are common and may be associated with cardiac ectopy, according to findings published in Diabetes Care.
“Patients who are treated with sulfonylureas to generally accepted glycemic targets frequently experience episodes and asyptomatic hypoglycemia,” Timothy L. Middleton, BSc, MBBS, MPhil, of the Diabetes Centre at Royal Prince Alfred Hospital and the department of medicine at the University of Sydney, told Endocrine Today. “These episodes are not necessarily benign from a cardiovascular perspective and this fact should be takin into consideration when making treatment decisions with patients.”
Middleton and colleagues evaluated 30 adults with well-controlled type 2 diabetes (mean HbA1c, 6.9%) treated with sulfonylureas who underwent 48 hours of concurrent continuous glucose monitoring and ambulatory electrocardiography to determine the effect of sulfonylurea-related hypoglycemia on cardiac repolarization and ectopy.
During periods of hypoglycemia (< 3.5 mmol/L for > 20 minutes), ventricular repolarization and QT dynamicity were analyzed and compared with periods of euglycemia and hyperglycemia combined.
Overall, nine participants experienced a total of 15 distinct hypoglycemia episodes during the study period. Gliclazide was the most common sulfonylurea treatment (n = 29), and one participant reported using glimepiride. The median daily dose of sulfonylurea did not differ between participants who experienced hypoglycemia and those who did (median dose, 60 mg).
Participants were asymptomatic in 73% of the hypoglycemic episodes; nine of 10 nocturnal episodes were asymptomatic. More hypoglycemic episodes that occurred during the day were symptomatic (3 of 5 episodes).
Compared with participants without hypoglycemic episodes, participants who experienced hypoglycemic episodes had higher nocturnal QT dynamicity (P = .01) and higher daytime QT dynamicity.
Rates of ventricular and supraventricular ectopy were increased during hypoglycemia.
“The study demonstrates that sulfonylurea-related hypoglycemia is an often under-recognized phenomenon for many patients and this is a phenomenon that may have adverse CV sequalae,” Middleton said. “It is not easy to predict which patients will experience adverse sequalae so when discussing type 2 diabetes treatment options, the potential for sulfonylurea therapy to prolong the QT interval during hypoglycemia and increased QT dynamicity should be taken into account. Perhaps it is time to place more emphasis on treatments with demonstrated CV safety.”
Middleton added that there is a need for larger, more detailed continuous glucose monitoring and holter monitoring studies to corroborate the study findings.
“Appropriate longitudinal follow-up will enable more definitive conclusions to be drawn, including determination of the strength and temporal association of hypoglycemia propensity with increased QT dynamicity, he said. – by Amber Cox
For more information:
Timothy L. Middleton, BSc, MBBS, MPhil, can be reached at timothy.middleton@sswahs.nsw.gov.au
Disclosure: Middleton reports receiving an Australian Diabetes Society-Merck Sharp & Dohme Corp. Travel Scholarship. Please see the full study for a list of all other authors’ relevant financial disclosures.
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