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Early, sustained glucose control lowers CVD risk in newly diagnosed type 2 diabetes

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December 5, 2017

Patients with type 2 diabetes who achieve early and sustained HbA1c control between 6.5% and 7% were substantially less likely to experience a cardiovascular event vs. patients who maintain either aggressive or poor glycemic control, according to findings published in Current Medical Research and Opinion.

Results from several landmark trials have demonstrated possible differences in CVD risk reduction between patients with type 2 diabetes who have good glycemic control early on vs. those with poor control for a longer duration, Carlos I. Alatorre, director of research at Eli Lilly, and colleagues wrote in the study background. Additionally, they noted aggressive glucose control, typically defined as HbA1c 6.5% or less, was shown to increase macrovascular risk in patients with a longer diabetes duration and those with poor control at the time of the intensive therapy initiation.

“These observations suggest that interventions designed to reduce CVD and mortality risk may be different in patients with early diabetes disease than those with more established disease,” Alatorre and colleagues wrote. “However, studies investigating the association of factors with CV event risk early in the diabetes disease process are largely lacking, particularly those evaluating a broad set of factors in patients from real-world clinical practice with early and sustained glycemic control.”

In a nested, case-control study, researchers analyzed data from 11,426 patients with newly diagnosed type 2 diabetes, using data from the Clinical Practice Research Database from 1990 to 2012. Included patients attained an HbA1c of 8% or lower no later than 1 year after their diabetes diagnosis and maintained that level throughout the exposure period. Cases were identified by first occurrence of stroke, myocardial infarction, ischemic heart disease, unstable angina or death from any cause within 5 years after an HbA1c of 8% or lower was first reached after their diabetes diagnosis. Controls were sampled from the at-risk population; they were CV event-free at the time an incident case occurred and were randomly matched 4:1 to cases using index date, exposure time, age, sex and HbA1c at index.

Total observation period included 1 year before diabetes diagnosis (pre-diagnosis period), followed by up to 1 year from diabetes diagnosis to the index date (pre-index period) and up to 5 years of exposure after the index date (exposure period).

Within the 11,426-patient case cohort, 5,261 experienced a CV event, and 6,165 died. Among cases with a CV event, 2,127 (40%) experienced stroke, 1,525 (29%) ischemic heart disease, 1,160 (22%) MI and 449 (9%) unstable angina.

Researchers observed a U-shaped association between HbA1c values during the exposure period and the risk for CV events. Compared with patients with mean HbA1c between 6.5% and 7%, patients with HbA1c 6% or less had an HR of 1.3 (P = .0003), patients with mean HbA1c between 6% and 6.5% had an HR of 1.12 (P = .0263), patients with mean HbA1c between 7% and 7.5% had an HR of 1.68 (P < .0001) and patients with mean HbA1c between 7.5% and 8% had an HR of 10.52 (P < .0001).

Researchers also found that baseline use of antiplatelet medications was associated with increased risk for stroke (HR = 1.82; 95% CI, 1.6-2.06), MI (HR = 1.67; 95% CI, 1.38-2.03) and ischemic heart disease (HR = 1.85; 95% CI, 1.57-2.17).

“Sustained glycemic intervention from early in the disease process is associated with a reduced risk of CV events in patients newly diagnosed with [type 2 diabetes],” the researchers wrote. “In particular, maintaining HbA1c between 6.5% and 7% appears to confer the most optimal cardioprotective effects in real-world clinical practice vs. higher glycemia or overly aggressive glycemic control. These findings confirm the importance of early, adequate and sustained glycemic intervention in routine clinical practice for people with diabetes and are particularly valuable to help improve patient outcomes and reduce the significant burden of illness and societal impact of diabetes.” – by Regina Schaffer

Disclosures: Eli Lilly and Company funded this study.