**Background:** Type 2 diabetes (T2D) is a complex metabolic disorder affecting 1 in 10 adults globally, with over 50% of cases in the Asia-Pacific region. Hyperglycemia drives microvascular and macrovascular complications and premature mortality. Despite new glucose-lowering drugs (GLDs), glycemic control remains suboptimal worldwide. Cardiovascular outcome trials (CVOTs) have demonstrated cardiorenal benefits of SGLT2 inhibitors and GLP-1 receptor agonists, but these trials enrolled high-risk patients and did not fully address the role of glycemic control. This narrative review, based on a symposium at the IDF Virtual Congress 2021, examines the importance of early glycemic control, the legacy effect, and the need for a balanced treatment approach incorporating both glucocentric and cardiorenal risk reduction, supplemented by real-world evidence from Asia.
**Methods:** This is a narrative review of published literature, including landmark trials (UKPDS, ADVANCE, ACCORD, VADT, VERIFY, J-DOIT3, LEADER, REWIND), meta-analyses, and real-world data from the Joint Asia Diabetes Evaluation (JADE) Register. The JADE Register is a web-based portal that has enrolled over 120,000 patients from 11 Asian countries/areas since 2007. A retrospective cross-sectional analysis of 62,512 patients with T2D (enrolled 2007–2019) was used to examine sulfonylurea (SU) usage patterns and associated outcomes. The review does not include new human or animal studies.
**Key Results:** The UKPDS showed that intensive glycemic control (HbA1c 7.0% vs. 7.9%) reduced microvascular complications by 25% (p=0.0099) and myocardial infarction by 16% (p=0.052) over 10 years. The legacy effect persisted post-trial: 10-year follow-up showed continued risk reduction for microvascular complications (24%, p=0.001) and emergent reductions in myocardial infarction (15%, p=0.01) and all-cause mortality (13%, p=0.007). In UKPDS 88, a 1% lower HbA1c from diagnosis was associated with an 18.8% risk reduction in all-cause mortality 10–15 years later, whereas delaying this reduction by 10 years yielded only a 2.7% reduction. The ADVANCE study (37% Asian) found intensive control (HbA1c 6.5% vs. 7.3%) reduced the composite of macrovascular and microvascular events by 10%, driven by a 21% reduction in kidney disease. The VERIFY study showed early combination therapy (vildagliptin + metformin) reduced the risk of glycemic deterioration by 49% (HR 0.51; 95% CI 0.45–0.58; p<0.0001) versus metformin monotherapy. Meta-analyses of CVOTs reported that SGLT2 inhibitors reduced MACE by 10% (HR 0.90; 95% CI 0.85–0.95) and GLP-1 receptor agonists by 14% (HR 0.86; 95% CI 0.79–0.94; p=0.006). In the JADE Register, among 62,512 patients, 60% were treated with SUs; gliclazide was the most common SU in several Asian countries. Gliclazide users were 9% more likely to achieve HbA1c <7.0% and had a 19% lower risk of self-reported hypoglycemia compared with other SUs (adjusted for covariables).
**Clinical Implications:** Early and intensive glycemic control is critical for long-term prevention of complications and mortality in T2D, supporting a glucocentric approach. However, cardiorenal risk reduction with newer agents (SGLT2 inhibitors, GLP-1 receptor agonists) is also important, especially in high-risk patients. Given the high prevalence of T2D and resource limitations, affordable older drugs like metformin and sulfonylureas (particularly gliclazide) remain essential, as they are effective, safe, and endorsed by the WHO. Real-world data from Asia confirm that SUs are widely used and that gliclazide offers advantages in glycemic control and hypoglycemia risk. Treatment should be individualized based on patient age, weight, comorbidities, duration of diabetes, and affordability, as recommended by international and regional guidelines (ADA/EASD, IDF, Japanese, Chinese, Korean). The review emphasizes the need for systematic data collection and personalized care to improve outcomes.