Table 1.
Microvascular Outcomes in the Intention-to-Treat Analysis.*
| Outcome | Glargine (N =1263) | Glimepiride (N = 1254) | Liraglutide (N = 1262) | Sitagliptin (N = 1268) | Total (N = 5047) |
|---|---|---|---|---|---|
| Moderately increased albuminuria level † | |||||
| No. of participants/no. at risk (%) | 136/1066(12.8) | 135/1046 (12.9) | 121/1040(11.6) | 115/1070(10.7) | 507/4222 (12.0) |
| Rate (95% Cl) — events/100 participant-yr | 2.76 (2.32–3.26) | 2.78 (2.33–3.29) | 2.46 (2.05–2.95) | 2.30 (1.90–2.76) | 2.57 (2.35–2.81) |
| Pairwise hazard ratio (95% Cl) | |||||
| Glargine | 1.00 (0.78–1.26) | 1.12 (0.88–1.43) | 1.20 (0.94–1.54) | ||
| Glimepiride | 1.12 (0.88–1.44) | 1.21 (0.94–1.55) | |||
| Liraglutide | 1.07 (0.83–1.39) | ||||
| Sitagliptin | |||||
| Hazard ratio (95% Cl) in one agent as compared with the others combined | 1.10 (0.91–1.34) | 1.11 (0.91–1.35) | 0.95 (0.77–1.16) | 0.86 (0.70–1.06) | |
| Severely increased albuminuria level ‡ | |||||
| No. of participants/no. at risk (%) | 59/1240(4.8) | 64/1220 (5.2) | 70/1229 (5.7) | 66/1246 (5.3) | 259/4935 (5.2) |
| Rate (95% Cl) — events/100 participant-yr | 0.97 (0.74–1.26) | 1.08 (0.83–1.38) | 1.17 (0.91–1.48) | 1.09 (0.85–1.39) | 1.08 (0.95–1.22) |
| Pairwise hazard ratio (95% Cl) | |||||
| Glargine | 0.90 (0.63–1.28) | 0.83 (0.59–1.18) | 0.89 (0.63–1.26) | ||
| Glimepiride | 0.92 (0.66–1.29) | 0.99 (0.70–1.39) | |||
| Liraglutide | 1.07 (0.76–1.50) | ||||
| Sitagliptin | |||||
| Hazard ratio (95% Cl) in one agent as compared with the others combined | 0.87 (0.65–1.17) | 1.00 (0.76–1.33) | 1.12 (0.85–1.47) | 1.02 (0.77–1.35) | |
| Renal impairment § | |||||
| No. of participants/no. at risk (%) | 144/1174 (12.3) | 151/1198 (12.6) | 170/1184 (14.4) | 145/1208 (12.0) | 610/4764 (12.8) |
| Rate (95% Cl) — events/100 participant-yr | 2.78 (2.35–3.28) | 2.88 (2.44–3.38) | 3.26 (2.79–3.78) | 2.73 (2.31–3.22) | 2.91 (2.69–3.15) |
| Pairwise hazard ratio (95% Cl) | |||||
| Glargine | 0.96 (0.76–1.20) | 0.85 (0.69–1.07) | 1.02 (0.81–1.28) | ||
| Glimepiride | 0.89 (0.72–1.11) | 1.07 (0.85–1.34) | |||
| Liraglutide | 1.19(0.95–1.49) | ||||
| Sitagliptin | |||||
| Hazard ratio (95% Cl) in one agent as compared with the others combined | 0.94 (0.78–1.13) | 1.00 (0.83–1.20) | 1.16 (0.97–1.38) | 0.92 (0.76–1.11) | |
| Diabetic peripheral neuropathy | |||||
| No. of participants/no. at risk (%) | 393/751 (52.3) | 427/728 (58.7) | 382/704 (54.3) | 405/723 (56.0) | 1607/2906 (55.3) |
| Rate (95% Cl) — events/100 participant-yr | 15.57 (14.07–17.19) | 18.22 (16.53–20.04) | 16.06 (14.49–17.75) | 16.87 (15.27–18.60) | 16.66 (15.85–17.49) |
| Pairwise hazard ratio (95% Cl) | |||||
| Glargine | 0.85 (0.74–0.97) | 0.96 (0.84–1.11) | 0.92 (0.80–1.06) | ||
| Glimepiride | 1.14 (0.99–1.31) | 1.08 (0.95–1.24) | |||
| Liraglutide | 0.95 (0.83–1.10) | ||||
| Sitagliptin | |||||
| Hazard ratio (95% Cl) in one agent as compared with the others combined | 0.91 (0.81–1.02) | 1.13 (1.01–1.27) | 0.96 (0.85–1.07) | 1.02 (0.91–1.14) |
The number of participants at risk excludes the prevalent cases at baseline that were not counted in either the numerator or denominator of the calculation of the rate. Pairwise hazard ratios were calculated from an analysis of the differences in the hazards among any of the four treatment groups, on the basis of a Cox proportional-hazards model, with treatment group as the only predictor variable. The 95% confidence intervals (CIs) were not corrected for multiple comparisons.
A moderately increased albuminuria level was defined as a confirmed urinary albumin:creatinine ratio of at least 30, as measured in milligrams of albumin to grams of creatinine.
A severely increased albuminuria level was defined as a urinary albumin:creatinine ratio of at least 300, as measured in milligrams of albumin to grams of creatinine.
Impaired renal function was defined as an estimated glomerular filtration rate of less than 60 ml per minute per 1.73 m2. Participants in whom incident end-stage kidney disease (as defined by dialysis, transplantation, or death from kidney disease) developed during the trial were considered to have had an outcome event in the categories of albuminuria (moderately increased albuminuria and severely increased albuminuria) and renal impairment.