Introduction and Objective: While clinical trials have established legacy effects in diabetes management, real-world evidence on how historical glycaemic exposures affect survival and critical time windows is limited. We evaluated the legacy effect of glycaemic exposure on all-cause mortality among newly diagnosed type 2 diabetes (T2D).Methods: This was a retrospective cohort of 52,404 newly diagnosed T2D patients in Hong Kong in 2000-2019. We assessed 10-year mortality hazard functions and estimated the time-varying impact of historical HbA1c exposures using a weighted cumulative exposure model, adjusting for potential confounders.Results: Among 52,404 patients (mean age: 58±11 years; 46% female; mean HbA1c at diagnosis: 9.0%±2.5%), 2,918 died during a median follow-up of 6.3 years. Over a hypothetical 10-year period, a sustained 1% reduction in HbA1c was associated with a 25% lower all-cause mortality risk (adjusted hazard ratio [HR]=0.75; 95% confidence interval [CI]: 0.70-0.79), whereas delaying this reduction until 5 years post-diagnosis resulted in only a 7% lower risk (HR=0.93, 0.87-0.99). The first 2 years post-diagnosis were critical. The risk reductions for achieving 1% HbA1c reduction during specific time frames, years 1-2, 3-4, 5-6, 7-8, and 9-10 after diagnosis, were 14% (HR=0.86,0.84-0.88), 3% (HR=0.97, 0.94-0.98), 1% (HR=0.99, 0.97-1.01), 3% (HR=0.97, 0.95-0.99), and 6% (HR=0.94, 0.90-0.96).Conclusion: In this real-world study, both early and recent HbA1c exposures significantly contributed to mortality risk in newly diagnosed T2D. The first 2 years post-diagnosis were critical, with at least 1% HbA1c reduction within the first 2 years of diagnosis associated with a 14% reduction in the 10-year mortality risk. These findings highlight the importance of initiating and maintaining intensive glycaemic control immediately after diagnosis to maximize long-term survival benefits.
A. Yang: None. X. Zhang: None. M. Shi: None. H. Wu: None. E. Lau: None. J. Yu: None. B. Fan: None. Y. Huang: None. J.N.M. Lui: None. A.P. Kong: Advisory Panel; Abbott. Speaker’s Bureau; Abbott, AstraZeneca, Zuellig Pharma. Advisory Panel; Biomea Fusion. Speaker’s Bureau; Dexcom, Inc. Advisory Panel; Eli Lilly and Company. Other Relationship; Elsevier. Research Support; Sanofi. Advisory Panel; Kyowa Kirin Co., Ltd. A. Luk: Research Support; Roche Pharmaceuticals. Other Relationship; Eli Lilly and Company. Research Support; Merck Sharp & Dohme Corp, AstraZeneca. Other Relationship; Novo Nordisk. Research Support; Amgen Inc. R.C. Ma: Advisory Panel; AstraZeneca. Other Relationship; AstraZeneca, Bayer Pharmaceuticals, Inc. Advisory Panel; Boehringer-Ingelheim. Other Relationship; Boehringer-Ingelheim. Advisory Panel; Eli Lilly and Company. Research Support; Novo Nordisk, Boehringer-Ingelheim, Roche Diagnostics. Advisory Panel; Merck & Co., Inc. J.C. Chan: Consultant; Servier Laboratories, Bayer Pharmaceuticals, Inc, Roche Diabetes Care, Lilly Diabetes. Research Support; AstraZeneca. Other Relationship; Novo Nordisk Foundation. Research Support; Hua Medicine. Speaker’s Bureau; Zuellig Pharma. Research Support; Biolingus. Board Member; Asia Diabetes Foundation. Stock/Shareholder; GemVCare. Other Relationship; KDIGO. Research Support; Applied Therapeutics. Other Relationship; European Association for the Study of Diabetes. Consultant; Sanofi. E. Chow: Speaker’s Bureau; AstraZeneca, Boehringer-Ingelheim, Bayer Pharmaceuticals, Inc. Research Support; Medtronic. Speaker’s Bureau; Zuellig Pharma, Sinocare Inc. Research Support; Hua Medicine. Speaker’s Bureau; Procter & Gamble.
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