Table 1.
Overview of Gla-100 clinical trials in T1DM.
| References | Study Design | Sample Size | Trial Duration | Treatment | HbA1c Change from Baseline (Recorded in the same Order the Treatments have been Mentioned) | Frequency of Hypoglycemia (Recorded in the same Order the Treatments have been Mentioned) | Comment |
|---|---|---|---|---|---|---|---|
| Rossetti et al. (2003) [7] | - | 51 | 3 months | • NPH (four times/day) • Gla-100 (at dinner or bedtime) |
0.1% -0.4% -0.4% |
Symptomatic: 12.2 vs. 8.1 vs. 7.7 Nocturnal: 3.6 vs. 1.7 vs. 2.0 |
• Both result in good glycemic control • Gla-100 decreased the HbA1c level and frequency of hypoglycemia more vs. NPH |
| Fulcher et al. (2005) [8] | Multicenter, randomized, single-blind, controlled, parallel group study |
125 | 30 weeks | • Pre-prandial insulin lispro + Gla-100 • Pre-prandial insulin lispro + NPH at bedtime |
–1.04% –0.50% |
Mild: 10.78 vs. 10.34 events/100 patient days Severe: 0.87 vs. 0.99 events/100 patient days |
• Gla-100 is superior to NPH for improving HbA1c and FPG levels |
| Raskin et al. (2000) [9] | Phase III multicenter randomized open-label |
619 | 16 weeks | • Gla-100 • NPH |
-0.1% -0.1% |
Nocturnal: 59.3% vs. 59.0% Severe: 5.2% vs. 4.6% |
• Insulin Gla-100 once a day appears to be as safe and at least as effective as using NPH insulin once or twice a day |
| Rosenstock et al. (2000) [10] | Multi-center partially double-blind randomized parallel group controlled trial |
315 | 4 weeks | • Gla-100 + 30 μg/mL zinc • Gla-100 + 80 μg/mL zinc • NPH |
-0.4% -0.4% -0.4% |
93.2% 97.6% 100.0% |
• Gla-100 is safe and more effective in lowering fasting • Plasma glucose levels than NPH |
| Home et al. (2005) [11] | Randomized, multicenter, open-label, controlled, parallel group |
585 | 16 weeks | • Gla-100 • NPH |
0.21% 0.10% |
Nocturnal: 61.0% vs. 61.1% Severe: 10.6% vs. 15.0% |
• Gla-100 provided a level of glycemic control at least as effective as NPH |
| Porcellati et al. (2004) [12] | - | 121 | 1 year | • NPH four times/day • Gla-100 once daily at dinner time |
- | Mild: 13.2 ± 0.6 episodes/patient-month 7.2 ± 0.5 episodes/patient-month No episodes of severe hypoglycemia |
• Gla-100 appears more suitable than NPH as basal insulin |
| Herwig et al. (2007) [13] | Open, prospective investigation | 142 | 11 months | • Gla-100 • NPH/semilente |
No statistically significant between-treatment differences in HbA1c levels (P = 0.23) |
0.07 ± 0.32 events/patient-year 0.54 ±1.10 events/patient-year |
• Gla-100 is associated with equivalent glycemic control, less severe hypoglycemia and improved QoL compared with NPH/semilente insulin |
| Ratner et al. (2000) [14] | Multicenter randomized parallel-group study |
534 | 28 weeks | • Gla-100 (bedtime) • NPH (OD or BD) |
-0.16% (baseline 7.7%) -0.21% (baseline 7.7%) |
Nocturnal: 18.2% vs. 21.7% | • Lower FPG levels with fewer episodes of hypoglycemia with Gla-100 compared with OD or BD NPH |
| Witthaus et al. (2001) [15] | Randomized, controlled, open-label study |
517 | 28 weeks | • Gla-100 • NPH |
- | Significant difference in favor of insulin Gla-100 | • Significantly improved treatment satisfaction throughout the study |
| Bolli et al. (2009) [16] | Parallel, open-label, multicenter study of individuals switched from NPH |
175 | 4-week run-in, 24 weeks treatment |
• Lispro + Gla-100 (dinner time) • Lispro + NPH (bd) |
-0.56% -0.56% |
Total: 0.26 vs. 0.21 episodes/patient/month Nocturnal: -0.19 vs. -0.10 |
• Lower FPG, lower BG variability and reduced nocturnal hypoglycemia with Gla-100 • Greater satisfaction and lower cost with Gla-100 |
| Chatterjee et al. (2007) [17] | Open-label, single-center, two-period crossover study using a BBT regimen |
53 | 36 weeks | • Aspart + Gla-100 • Aspart + NPH (bd) |
-0.46% -0.26% |
NR | • Lower HbA1c and mean FPG (–54 mg/dL, P = 0.002), and greater satisfaction with Gla-100 compared with NPH (DTSQ, P = 0.001) |
| Derosa G, et al. (2015) [18] | Multicenter, randomized, double-blind trial | 49 | - | • Gla-100, Detemir or Lispro protamine | - | Ten symptomatic hypoglycemia events occurred during CGMS: one in insulin lispro protamine group, five in Gla-100 group, four in detemir group. |
• Mean BG was significantly higher with insulin detemir compared to Gla-100 (157.68 ± 61.36 vs. 149.04 ± 53.77, P < 0.05) • Glycemic variability parameter of M-value obtained with Gla-100 was lower compared to detemir between 17-18 (P < 0.01) • The SD of 24-hour blood glucose value was significantly lower with Gla-100 (P < 0.05) than with insulin detemir • Glycemic variability parameter of MODD value at 10-11 was lower with Gla-100 compared to detemir (P < 0.05) |
Abbreviations: BBT, basal bolus therapy; BD, twice daily; BG, blood glucose; CGM, continuous glucose monitoring; DTSQ, diabetes treatment satisfaction questionnaire; FPG, fasting plasma glucose; Gla-100, glargine 100 U/mL; HbA1c, glycated hemoglobin; MODD, mean of daily difference; NPH, neutral protamine Hagedorn; NR, not reported; OD, once daily; QoL, quality of life; SD, standard deviation.