BACKGROUND AND PURPOSE:

• The 20-year UK Prospective Diabetes Study (UKPDS) found that individuals who underwent an intensive glycemic control strategy with sulfonylurea or insulin therapy or metformin therapy had better outcomes than those who controlled glycemic levels through diet alone
  • A 10-year follow-up highlighted the long-term benefits of intensive therapy
• Adler et al. (The Lancet, 2024) determined whether the benefits of intensive glycemic control would wane after another 14 years of follow-up

METHODS:

• Extended follow-up of randomized controlled trial
• Participants
  • Individuals with diabetes
• Original intervention (over 20 year period)
  • Intensive glycemic control (sulfonylurea or insulin, or metformin if BMI >27 kg/m2)
  • Conventional glycemic control (primarily diet)
• Study design
  • This study reports on an additional 14 years of follow-up after the initial 10-year post-trial monitoring period
  • Kaplan–Meier time-to-event and log-rank analyses were used
• Primary outcomes
  • Aggregate clinical outcomes
    • Any diabetes-related endpoint | Diabetes-related death | Death from any cause | Myocardial infarction | Stroke | Peripheral vascular disease | Microvascular disease

RESULTS:

• 1489 participants (of 3277 individuals surviving at the start of the initial 10-year follow-up)
  • Mean age at baseline: 50.2 (SD, 8.0) years | Mean age in 2021: 79.9 (IQR, 12.3 to 26.8)
  • Female: 41.3%
• For up to 24 years after trial end, the glycemic and metformin legacy effects showed no sign of waning
• Those allocated to early intensive glycemic control with sulfonylurea or insulin therapy had overall lower risks of
  • Death from any cause: Relative Risk (RR) 0.90 (95% CI, 0.83 to 0.98) | P=0.015
  • Myocardial infarction: RR 0.83 (95% CI, 0.74 to 0.94) | P=0.002
  • Microvascular disease: RR 0.76 (95% CI, 0.64 to 0.89) | P<0.0001
• Early intensive glycemic control with metformin therapy led to overall risk reductions for
  • Death from any cause: RR 0.80 (95% CI, 0.68 to 0.95) | P=0.010
  • Myocardial infarction: RR 0.69 (95% CI, 0.54 to 0.88) | P=0.003
• There were no significant differences in risk of stroke or peripheral vascular disease during or after the trial
  • There was no risk reduction for microvascular disease with metformin therapy

CONCLUSION:

• For patients with type 2 diabetes, early intensive glycemic control confers near life-long risk reduction in all-cause mortality, microvascular complications and myocardial infarction
• The authors state

The legacy benefits from early intensive glycaemic control with sulfonylurea or insulin led to overall relative risk reductions from baseline of 10% for death, 17% for myocardial infarction, and 26% for microvascular complications

Early intensive glycaemic control with metformin led to numerically larger overall relative risk reductions than with sulfonylurea or insulin, from baseline of 20% for death and 31% for myocardial infarction

Achieving near-normal glycaemia immediately after type 2 diabetes is diagnosed appears to be essential to minimise the lifetime risk of diabetes-related complications to the greatest extent possible

Learn More – Primary Sources:

Post-trial monitoring of a randomised controlled trial of intensive glycaemic control in type 2 diabetes extended from 10 years to 24 years (UKPDS 91)