A bidirectional relationship between severe hypoglycemic events (SHEs) and cardiovascular (CV) outcomes suggests a common “frail” type 2 diabetes phenotype of patients who are susceptible to both of these events, according to a study published in Diabetes Care.1

While previous trials have demonstrated an association between SHEs and subsequent CV events in patients with type 2 diabetes,2-6 researchers sought to determine whether CV events are associated with subsequent SHE risk in this same population.1

Using data from the TECOS trial (Trial Evaluating Cardiovascular Outcomes With Sitagliptin; ClinicalTrials.gov identifier: NCT00790205) in 14,671 participants with type 2 diabetes and CV disease, post hoc analyses were conducted to evaluate time-dependent associations between SHEs and a composite CV end point (fatal/nonfatal myocardial infarction or stroke, hospitalization for unstable angina, and hospitalization for heart failure [hHF]).

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Participants received either sitagliptin 100 mg daily (or 50 mg daily if baseline estimated glomerular filtration rate (eGFR) was ³30 and <50 ml/min/1.73 m2) or matching placebo and were followed for a median of 3 years.

The researchers found that SHEs were uncommon and unassociated with sitagliptin therapy and that patients with SHEs were older with a longer duration of diabetes, lower body weight, and a lower eGFR. These patients were also more likely to be women, non-white, receiving insulin therapy, and more often had micro- or macroalbuminuria.

SHEs were associated with an increased risk for the composite CV end point, all-cause death, and CV death, and nonfatal myocardial infarction, nonfatal stroke, and hHF were associated with an increased risk for SHEs.

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The investigators concluded that “SHEs, rather than being causative of [major adverse cardiovascular events], hHF, or all-cause death events, may simply be indicative of patients with a frail type 2 diabetes phenotype who are at high risk of both outcomes likely due to a multitude of coexisting risk factors.”1

Disclosure: The TECOS trial was funded by Merck Sharp & Dohme Corp.


  1. Standl E, Stevens SR, Armstrong PW, et al; TECOS Study Group. Increased risk of severe hypoglycemic events before and after cardiovascular outcomes in TECOS suggests an at-risk type 2 diabetes frail patient phenotype [published online January 8, 2018]. Diabetes Care. doi:10.2337/dc17-1778
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