Adults with type 2 diabetes and cardiovascular disease who experience a severe hypoglycemic episode are at increased risk for a nonfatal CV event or hospitalization for unstable angina, nonfatal myocardial infarction, nonfatal stroke or heart failure, study data show.
“Our findings seem to suggest a new perspective in dealing with severe hypoglycemic events complicating blood glucose-lowering therapy,” Eberhard Standl, MD, PhD, professor of medicine at the Munich Diabetes Research Group e.V. at Helmholtz Centre in Germany, told Endocrine Today. “Whilst 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. 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.”
Standl and colleagues evaluated data from the TECOS trial on 14,671 adults with type 2 diabetes and CVD to determine whether CV events are associated with subsequent risk for severe hypoglycemic events. Median follow-up was 3 years. Participants in TECOS were randomly assigned to placebo or sitagliptin (Januvia, Merck).
Among participants with severe hypoglycemic events (n = 303), mean age at study randomization was 67 years, 63.7% were men, 58.1% were white and mean duration of diabetes was 14 years. Among participants without severe hypoglycemic events (n = 14,368), mean age at study randomization was 65 years, 70.9% were men, 68.1% were white and mean duration of diabetes was 10 years.
Overall, severe hypoglycemic events were uncommon, with 2.1% of participants reporting one or more event. No difference was observed in incidence of severe hypoglycemic events between participants assigned to sitagliptin or placebo.
A 4-point major adverse CV event or hospitalization for heart failure occurred in 68 (22.4%) participants with a severe hypoglycemia event. Among them, 34 had a prior severe hypoglycemic event and subsequent major adverse CV or hospitalization for heart failure event; 38 had a 4-point major adverse CV or hospitalization for heart failure event with a subsequent severe hypoglycemic event; and seven had a severe hypoglycemic event before and after a 4-point major adverse CV or hospitalization for heart failure event.
Subsequent 4-point major adverse CV event (HR = 1.57; 95% CI, 1.07-2.31), all-cause death (HR = 1.91; 95% CI, 1.27-2.88) and CV death (HR = 1.81; 95% CI, 1.08-3.02) were all associated with severe hypoglycemic events in unadjusted analyses; the associations remained significant after adjustment for selected demographic factors, but not after further adjustment for baseline variable associated with CV events.
After adjustment for clinical factors, nonfatal CV event or hospitalization for unstable angina (HR = 2.48; 95% CI, 1.65-3.75), nonfatal MI (HR = 3.02; 95% CI, 1.83-4.96), nonfatal stroke (HR = 2.77; 95% CI, 1.36-5.63) and heart failure (HR = 3.68; 95% CI, 2.13-6.36) were all associated with severe hypoglycemic events.
“Substantially greater risk of severe (assistance requiring) hypoglycemic events was uncovered after (non-fatal) CV events as a novel finding, in addition to the previously noted greater risk of CV events after severe hypoglycemic events in our post hoc analysis evaluating the TECOS cohort of 14,671 patients with type 2 diabetes and established CVD,” Standl said. “This bidirectional association suggests a common at-risk type 2 diabetes frail patient phenotype who is vulnerable to both severe hypoglycemic events and CV events.” – by Amber Cox
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Eberhard Standl, MD, PhD, can be reached at email@example.com.
Disclosures: Standl reports he receives personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Merck Serono-EXCEMED, Novartis, Novo Nordisk, Sanofi and the University of Oxford Diabetes Trials Unit. Please see the study for all other authors’ relevant financial disclosures.