Table 3.
Results achieved in clinical trials of basal insulin titration in insulin-naïve patients with type 2 diabetes using various basal insulin preparations in addition to well-defined single or combined oral glucose-lowering agents, trying to aim at different glucose-lowering agent treatments
| Oral glucose-lowering agents | Outcome parameter | Fasting plasma glucose | HbA1c | HbA1c <7% (53.0 mmol/mol) |
HbA1c ≤6.5% (47.5 mmol/mol) |
Hypoglycemia | Severe hypoglycemia | Daily insulin dose | Daily insulin dose | Body weight change from baseline |
| Unit | (mmol/L) | (%) (mmol/mol) |
Yes/No (% yes) | Yes/No (% yes) | Yes/No (% yes) | Yes/No (% yes) | (IU/day) | (IU/kg/day) | kg | |
| a. Results in groups defined by oral glucose-lowering agents/combinations employed | ||||||||||
| OGLM 1 | Metformin only | 6.4 (6.3 to 6.5) | 7.1 (7.1 to 7.2) 54.1 (54.1 to 55.2) |
1914/1988 (49.1) | 1013/2889 (26.0) | 1567/2113 (42.6) | 32/3870 (0.8) | 60 (59 to 60) | 0.65 (0.64 to 0.66) | 0.8 (0.7 to 1.0) |
| OGLM 2 | Sulfonylurea only | 7.1 (6.9 to 7.2)* | 7.7 (7.6 to 7.7)* 60.7 (59.6 to 60.7) |
438/881 (33.2)* | 237/3970 (5.6)* | 740/579 (56.1)* | 21/1298 (1.6)* | 36 (35 to 37)* | 0.43 (0.42 to 0.45)* | 2.7 (2.5 to 3.0)* |
| OGLM 3 | Metformin+ sulfonylureas± thiazolidinediones |
6.7 (6.6 to 6.7)*, †, ‡ | 7.2 (7.2 to 7.2)*,† 55.2 (55.2 to 55.2) |
4056/4854 (45.5)*, † | 2196/6714 (24.6)*, † | 4525/3362 (57.4)* | 96/8628 (1.1) | 39 (39 to 40)*, † | 0.43 (0.43 to 0.44)* | 2.1 (1.9 to 2.2)*,† |
| OGLM 4 | Metformin±DPP-4 inhibitors | 6.2 (6.2 to 6.3)*, †, ‡ | 7.0 (7.0 to 7.0)*, †, ‡ 53.0 (53.0 to 53.0) | 1668/1634 (50.5)†, ‡ | 993/2309 (30.1)*, †, ‡ | 1338/1963 (40.5)†,‡ | 27/3168 (0.8)† | 56 (55 to 57), *†, ‡ | 0.59 (0.58 to 0.60)*, †,‡ | 1.4 (1.2 to 1.5)*, †, ‡ |
| Overall significance (p value) | <0.0001 | <0.0001 | <0.0001 | <0.0001 | <0.0001 | 0.0632 | <0.0001 | <0.0001 | <0.0001 | |
| b: Differences between groups defined by oral glucose-lowering agents/combinations employed | ||||||||||
| Comparison | OGLM 1 vs 2 | 0.65 (0.52 to 0.78)§ | 0.53 (0.46 to 0.60)§ 5.8 (5.0 to 6.6) |
-15.8 (-18.8 to -12.8)§ | -8.0 (-10.5 to -5.4)§ | -13.5 (-16.7 to -10.4)§ | -0.8 (-1.4 to 0.1)§ | -§23 (-25 to -22)§ | -0.22 (-0.24 to -0.20)§ | 1.9 (1.63 to 2.19)§ |
| OGLM 1 vs 3 | 0.29 (0.21 to 0.36)§ | 0.05 (0.01 to 0.08)§ 0.5 (0.1 to 0.9) |
-4.0 (-5.9 to -2.1)§ | -10.6 (-12.2 to -9.0)§ | -14.8 (-16.8 to -12.9)§ | -0.3 (-0.7 to 0.1) | -20 (-21 to -19)§ | -0.22 (-0.23 to -0.21)§ | 1.20 (1.03 to 1.37)§ | |
| OGLM 1 vs 4 | -0.16 (-0.25 to -0.06)§ | -0.13 (-0.17 to -0.08)§ 1.4 (-1.9 to -0.9) |
-1.5 (-3.8 to 0.9) | -4.1 (-6.2 to -2.0)§ | -2.0 (-4.4 to 0.3) | 0.0 (-0.5 to 0.4) | -4 (-5 to -2)§ | -0.06 (-0.08 to -0.05)§ | 0.52 (0.33 to 0.71)§ | |
| OGLM 2 vs 3 | -0.37 (-0.49 to -0.24)§ | 0.48 (-0.55 to -0.41)§ 5.2 (-6.0 to -4.5) |
-11.9 (-14.7 to -9.1)§ | -2.6 (-5.0 to -0.4)§ | -1.3 (-4.2 to 1.7) | -0.5 (-1.4 to 0.1) | 3 (2 to 4)§ | 0.00 (-0.01 to 0.00) | -0.71 (-0.98 to -0.44)§ | |
| OGLM 2 vs 4 | -0.81 (-0.95 to -0.67) § | 0.66 (-0.73 to -0.59)§ 7.2 (-8.0 to -6.4) |
-17.3 (-20.5 to -14.3)§ | -12.1 (-14.8 to -9.5)§ | -15.6 (-18.7 to -12.4)§ | -0.7 (-1.7 to 0.0)§ | 20 (18 to 21)§ | 0.16 (0.14 to 0.18)§ | -1.39 (-1.68 to -1.10)§ | |
| OGLM 3 vs 4 | -0.44 (-0.54 to -0.35)§ | 0.18 (-0.22 to -0.14)§ 2.0 (-2.4 to -1.5) |
-5.4 (-7.4 to -3.4)§ | -14.7 (-16.5 to -12.9)§ | -16.8 (-18.8 to -14.8)§ | -0.3 (-0.6 to 0.2) | 17 (15 to 18) § | 0.16 (0.14 to 0.17)§ | -§0.68 (-0.87 to -0.49)§ | |
Continuous variables are presented as means and their 95% CIs, categorical variables are presented as number fulfilling/not fulfilling the criterion and the proportion (percentage) fulfilling the criterion in question. Statistical significance was assessed using one-way analysis of variance (Welch’s test) for continuous variables and χ2 test for larger than 2×2 contingency tables and Fisher’s exact test for 2×2 contingency tables (eg, post hoc tests to identify significant differences between specific titration targets), including the ‘attributable difference’ expressed as a percentage and its 95% CI. For overall comparisons, exact p values are presented.
*Significantly different (p<0.05) vs OGLM 1: metformin.
†Significantly different (p<0.05) vs OGLM 2: sulfonylurea.
‡Significantly different (p<0.05) vs OGLM 3: metformin, sulfonylureas and thiazolidinediones.
§: Significantly different (p< .05)
HbA1c, hemoglobin A1c.