Written by Peter Liu
Spoon Feed
More intensive glucose-lowering targets (HbA1c <6.5) may benefit patients with type 2 diabetes (T2DM), irrespective of age at diagnosis or duration of T2DM.
Intensive glycemic targets for a wide range of patients with T2DM
Glycemic targets are at the core of all important decisions regarding T2DM. Intensifying glycemic targets reduces microvascular complications (retinopathy, nephropathy, and peripheral neuropathy). However, overly intense glycemic targets result in increased mortality (i.e. ACCORD trial). In the middle (HbA1c between 6-7), intensifying blood sugar control probably also lowers some macrovascular complications, particularly nonfatal MI, at the cost of many severe hypoglycemic episodes per prevented MI.
This post-hoc analysis of the ADVANCE RCT investigated whether the effects of intensive glycemic targets differed by age at T2DM diagnosis or by T2DM duration. In ADVANCE, 11,138 participants were randomized to intensive glucose lower with addition of gliclazide (HbA1c target 6.5) or routine care. With an average follow-up period of five years, this post-hoc analysis demonstrated that intensive glucose lowering reduced major vascular events by 10% (HR 0.90, 95%CI 0.82–0.98) consistently across subgroups defined by age at diagnosis and diabetes duration (P for heterogeneity >0.4), mostly due to prevention of nephropathy. These results suggest that intensive glucose goals should be considered irrespective of age at diagnosis or duration of disease. However, such a broad statement requires more support than this study is able to give. The study does not appear to be powered to show differences among its subgroups of age and age of diabetes onset. Also, estimates of other hazards including stroke, all-cause death, and severe hypoglycemia seem to favor intensive glycemic targets in patients with shorter diabetes duration, while hazard of severe hypoglycemia strongly favors standard glucose control.
How does this change my practice?
These findings will prompt me to consider intensive glycemic targets in a wider subgroup of my patients with T2DM (HbA1c targets less 7). However, treatment requires careful consideration and discussion if the long-term benefits are worth the short-term risks.
Source
Intensive Glucose Lowering and Its Effects on Vascular Events and Death According to Age at Diagnosis and Duration of Diabetes: The ADVANCE Trial. Diabetes Care. 2024 Dec 11:dc241516. doi: 10.2337/dc24-1516. Epub ahead of print. PMID: 39661106
