medwireNews: An analysis of TECOS data highlights a bidirectional relationship between severe hypoglycemic events and adverse cardiovascular (CV) outcomes in patients with type 2 diabetes.
Rather than being a cause of major adverse cardiovascular events (MACE), severe hypoglycemia “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,” Eberhard Standl (Helmholtz Centre, Neuherberg, Germany) and co-authors remark.
They found that severe hypoglycemic events were uncommon among the 14,671 TECOS participants who had type 2 diabetes and established CV disease and occurred at a similar rate between the sitagliptin and placebo groups, at 2.2% versus 1.9%, or 0.78 versus 0.70 events per 100 patient–years.
Among the 303 participants with severe hypoglycemic events, 68 (22.4%) also had a MACE (CV death, nonfatal myocardial infarction [MI], nonfatal stroke, or hospitalization for unstable angina) or were hospitalized for heart failure (HF). Of these, 34 had a severe hypoglycaemic event first and 38 had a cardiac event first, while seven had a hypoglycaemic event both before and after a cardiac event and three reported both events on the same day.
The researchers report that severe hypoglycemic events were associated with significantly increased risks for all-cause death (HR=1.83), CV death (HR=1.72), and MACE (hazard ratio [HR]=1.55) after adjustment for age, sex, race, smoking status, and weight.
However, further adjustment for baseline variables that were significantly associated with CV events rendered these associations nonsignificant.
Conversely, hospitalization for HF (HR=3.68), nonfatal myocardial infarction (HR=3.02), nonfatal stroke (HR=2.77), and nonfatal CV events or hospitalization for unstable angina (HR=2.48) were associated with a significantly increased risk for severe hypoglycemic events that remained significant after further adjustment for the wider range of baseline variables.
Standl et al note that patients with severe hypoglycemia were older, more frequently women, non-White, and insulin treated, with longer diabetes duration, lower body weight, and lower estimated glomerular filtration rate (eGFR), than those without it.
And patients with severe hypoglycemic events who also experienced CV events had higher baseline rates of previous MI and HF, and more frequent use of cardiovascular drugs, and insulin together with a lower eGFR, than those who did not.
These between-group differences in baseline characteristics “again [allude] to a common particularly frail type 2 diabetes phenotype of patients susceptible to both [severe hypoglycemic events] and CV events or hospitalization for heart failure,” say the researchers.
“[W]hile it remains important to seek to minimize the risk of [severe hypoglycemic events] in people with type 2 diabetes, the focus on attaining good glycemic control to minimize the risk of diabetes complications should not be unduly compromised,” Standl et al write in Diabetes Care.
They add: “A precision medicine approach is required to delineate those with a frail phenotype who need special consideration from those likely to benefit from more aggressive glycemic targets.”
By Laura Cowen
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