Severe hypoglycemia and cardiovascular risk interrelated in type 2 diabetes

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  • Hypoglycemia risk should be considered when setting glycemic targets in type 2 diabetes (T2D).

Why this matters

  • Role of severe hypoglycemic episodes (SHEs) in cardiovascular (CV) events is unclear.

Study design

  • Post hoc analysis from Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) involving 14,671 patients with T2D and CV disease followed for a median of 3 years.
  • Funding: Merck & Co., Inc., Kenilworth, NJ, USA.

Key results

  • SHEs (ie, requiring assistance) did not differ between sitagliptin and placebo (2.2% vs 1.9%, respectively; HR, 1.12; P=.33).
  • Patients with SHEs were older, had longer diabetes duration, lower weight, more impaired kidney function, and were more frequently nonwhite, female, and insulin-treated.
  • Of 303 with SHEs, 22.4% had a major CV event or hospitalization for heart failure (hHF).
  • Of those 68, SHE preceded event in 34, followed event in 38, and did both in 7.
  • After adjustments, associations between SHEs and subsequent CV events lost significance.
  • However, associations between nonfatal CV events and subsequent SHEs remained significant after adjustments, including CV event or unstable angina hospitalization (adjusted HR [aHR], 1.96; P=.001), myocardial infarction (2.31; P=.001), stroke (2.07; P=.046), hHF (2.26; P=.005).


  • Post hoc evaluation.
  • Low SHE rates.
  • Possible confounding from therapy changes after events.