. Author manuscript; available in PMC: 2024 Dec 18.

Published in final edited form as: Nat Rev Endocrinol. 2020 Oct 20;16(12):717–730. doi: 10.1038/s41574-020-00425-6

Table 1 |.

Summary of the major findings in guideline-defining trials

Study (year)	Diabetes mellitus type	Intensive glycaemic control target	HbA_1c achieved (%)^a	Microvascular outcomes	Macrovascular events	Mortality	Adverse events	Ref.
DCCT (1993)	T1DM	HbA_1c <6.05%	Mean 7.4 vs 9.1	Sustained retinopathy: RRR 76% (95% CI 62–85%) Microalbuminuria >40 mg/24 h: RRR 34% (95% CI 2–56%) Neuropathy: RRR 69% (95% CI 24–87%)	No significant difference	No significant difference	Hypoglycaemia: 62 per 100 patient-years (intensive) vs 19 per 100 patient-years (conventional) Weight gain: 33% (intensive) vs 9.3% (conventional)	¹³
UKPDS (1998) (SU, basal insuLin)^b	T2DM	FPG <110 mg/dl in the intensive arm vs FPG <270 mg/dlin the control arm	Median 7.0 vs 7.9	Combined microvascular: RRR 25% (95% CI 7–40%)	No significant difference	No significant difference	Weight gain: 3.1 kg (95% CI −0.9 to 7 kg)	²²
UKPDS (1998) (metformin)^b	T2DM	FPG <110 mg/dl in the intensive arm vs FPG <270 mg/dlin the control arm	Median 7.4 vs. 8.0	AnyT2DM-re1ated end point: RRR 32% (95% CI 13–47%) Retinopathy: minimal slowing of progression, but not sustained	Myocardial infarction: RRR 39% (P = 0.01) Composite macrovascular diseases: RRR 30% (95% CI 5–48%)	Any T2DM-related death: RRR 42% (95% CI 9–63%) All-cause mortality: RRR 36% (95% CI 9–55%)	96% increased risk of T2DM-re1ated death; 60% increased risk of mortality with early addition of metformin to sulfonylurea therapy	²³
ACCORD (2008)	T2DM	HbA_1c <6.0%	Median 6.4 vs 7.5	No significant difference	MACE: HR 0.90 (95% CI 0.78–1.04) Non-fatal MI: HR 0.76 (95% CI 0.62–0.92) Death from CV causes: HR 1.35 (95% CI 1.04–1.76)	All-cause mortality: HR 1.22 (95% CI 1.01–1.46)	Increased risk of hypoglycaemia requiring any assistance (16.2% vs. 5.1%) Weight gain: 3.5 kg vs 0.4 kg	²⁵
ADVANCE (2008)	T2DM	HbA_1c <6.5%	Mean 6.5 vs 7.3	Major microvascular events: HR 0.86 (95% CI 0.77–0.97) Renal events: HR 0.79 (95% CI 0.66–0.93) No significant difference in neuropathy or retinopathy	No significant difference	No significant difference	Hypoglycaemia: HR 1.86 (95% CI 1.42–2.4), although hypoglycaemia events were uncommon at 2.7% (intensive) and 1.5% (control)	²⁷
VADT (2009)	T2DM	Absolute HbA_1c reduction of 1.5%	Median 6.9 vs. 8.4	Any increase in albuminuria: 9.1% (intensive) vs. 13.8% (control) (P=0.01)	No significant difference	No significant difference	Any serious AE: 24.1% (intensive) vs 17.6% (control) (P=0.05) Hypoglycaemia significantly increased in the intensive group BMI 33.8 kg/m² vs 32.3 kg/m² (P = 0.01)	³¹

This is a revised summary table; the full table is available as Supplementary Table 1. ACCORD, Action to Control Cardiovascular Risk in Diabetes; ADVANCE, Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; AE, adverse event; BMI, body mass index; CV, cardiovascular; DCCT, Diabetes Control and Complications Trial; FPG, fasting plasma glucose; HbA_1c, glycated haemoglobin; HR, hazard ratio; MACE, major adverse cardiac event (defined as time to first major cardiovascular event: non-fatal myocardial infarction, non-fatal stroke or death from cardiovascular disease); MI, myocardial infarction; RRR, relative risk reduction; SU, sulfonylurea; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; UKPDS, UK Prospective Diabetes Study; VADT, Veterans Affairs Diabetes Trial.

Intensive arm versus control arm.

UKPDS trial results are stratified according to whether the intensive intervention arm used sulfonylurea or basal insulin, or metformin.