Intensive glucose lowering reduces vascular, mortality risk in type 2 diabetes
Key takeaways:
- Intensive glucose lowering reduced mortality and cardiovascular death risk significantly among patients with diabetes.
- The effects of intensive glucose lowering were consistent across all subgroups.
Regardless of age at diagnosis or duration of disease, patients with diabetes who underwent intensive glucose lowering had lower risk for vascular events and death, according to a post hoc analysis published in Diabetes Care.
Prior research has shown that patients diagnosed with diabetes at a younger age as well as patients with a longer duration of diabetes are at increased risk for vascular complications and death, according to the researchers, who theorized that these patients would experience greater benefits from intensive glucose control.
“However, randomized comparisons of the effectiveness of intensive glucose lowering on clinical outcomes between patients with younger- and older-onset diabetes, or with shorter and longer diabetes duration, are scarce,” Toshiaki Ohkuma, PhD, visiting research fellow and diabetologist with The George Institute for Global Health at the University of New South Wales in Sydney, New South Wales, Australia, and colleagues wrote.
To answer that question, the researchers performed an post hoc analysis of ADVANCE, a factorial randomized controlled trial which included 11,140 patients (mean age, 65.8 years; 42.5% women) with type 2 diabetes at high risk for cardiovascular events. Patients received either gliclazide intensive blood glucose control, with a target HbA1c of 6.5% or lower, or standard glucose control according to local guidelines.
Researchers classified participants into subgroups based on age at diagnosis (age ≤ 50 years, 50-60 years, ˃ 60 years) and duration of diabetes (≤ 5 years, 5-10 years, ˃10 years).
The primary endpoint was a composite of major macrovascular (death from CV causes, nonfatal myocardial infarction or nonfatal stroke) and microvascular (new or worsening nephropathy or retinopathy) events.
Median follow-up was 5 years.
Of the 11,138 participants included in the analysis, those diagnosed with diabetes at a younger age were more likely to be younger, have a longer diabetes duration and have a history of microvascular disease. Patients with a longer diabetes duration were more likely be older and to have been diagnosed at a younger age.
The researchers found that intensive glucose lowering reduced composite risk for vascular events by 10% (HR = 0.9; 95% CI, 0.82-0.98), with similar results seen across the different age at diagnosis and disease duration subgroups.
Further, the researchers found that intensive glucose lowering reduced all-cause mortality risk by 6% (95% CI, –6 to 17) and CV death risk by 12% (95% CI, –4 to 26). It also lowered risk for major macrovascular events by 6% (95% CI, –6 to 16) and risk for major microvascular events by 14% (95% CI, 3-23), again with similar results among the subgroups.
However, risk for hypoglycemia increased significantly across all subgroups with intensive glucose lowering (HR = 1.86; 95% CI, 1.42-2.44).
Ohkuma and colleagues noted several limitations to this analysis, including that the previous diabetic treatment received by patients in the ADVANCE trial may differ compared with contemporary patients.
“The present findings suggest that a more intensified glucose-lowering approach may be required in younger-onset or longer diabetes duration, although careful consideration of the combination of therapies being used is needed to prevent the occurrence of hypoglycemia,” Ohkuma and colleagues wrote.
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