QTc
Prolongation and the Sympathoadrenal Response to Hypoglycaemia in Diabetes: A Systematic Review and Meta‐Analysis
Annina Burgherr, Esther Su Wee Tan, Anika Jacobi, Thomas Pilgrim, Martina Rothenbühler, Benjamin Victor Ineichen, Lilian Witthauer ABSTRACT
Aims
To quantify changes in the heart rate‐corrected QT interval (QTc) and concurrent sympathoadrenal responses during induced and spontaneous hypoglycaemia in people with Type 1 or Type 2 diabetes.
Materials and Methods
PubMed and the Cochrane Library were searched from January 1990 to January 2026, restricted to English‐language publications. Random‐effects meta‐analyses compared hypoglycaemic and euglycaemic states by setting, with subgroup and sensitivity analyses for diabetes type, QT correction method and analytical assumptions.
Results
Across 32 studies, QTc prolongation was 44.0 ms (95% CI: 24.3–63.6) under induced and 16.4 ms (6.7–26.0) under spontaneous hypoglycaemia. Estimates were similar in Type 1 diabetes (27.2 ms, 12.9–41.5) and Type 2 diabetes (27.0 ms, 12.3–41.7). The all‐study summary was 30.2 ms (17.9–42.4; 95% prediction interval −40.9 to 101.3; I 2 = 98.4%). Heart rate rose by 5.0 bpm, systolic blood pressure by 3.1 mmHg, epinephrine by 1.75 nmol/L and norepinephrine by 0.66 nmol/L, while diastolic blood pressure fell by 4.4 mmHg and serum potassium by 0.44 mmol/L, all significantly. Only epinephrine change correlated with QTc change across studies after correction for multiple testing ( ρ = 0.87).
Conclusions
Hypoglycaemia was associated with QTc prolongation during spontaneous episodes and under clamp conditions, in both diabetes types, alongside concurrent sympathoadrenal changes. The direction of the association was robust to all sensitivity analyses; its magnitude varied substantially between studies. Mean hypoglycaemic QTc exceeded 450 ms in six studies. Hypoglycaemia avoidance remains a safety consideration in patients with pre‐existing repolarisation vulnerability or concomitant QT‐prolonging medication.