Table 2.
Overview of Gla-300 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 |
|---|---|---|---|---|---|---|---|
| Danne et al. [2020] [19] | Noninferiority, open-label, two-arm, parallel-group, phase 3b trial. | 463 | 26 weeks | • Gla-300 • Gla-100 |
-0.40% [0.06%] for both groups | Severe: 6.0% with Gla-300 and 8.8% with Gla-100 Any hyperglycemia with ketosis was 6.4% with Gla-300 and 11.8% with Gla-100. |
• Gla-300 provided similar glycemic control and better safety to Gla-100 in children >6 yrs and adolescents with T1DM. |
| Miura et al. (2020) [20] | Multicenter, crossover trial | 46 | 4 weeks | • IDeg-100-first/Gla-300-second group or the Gla-300-first/IDeg-100-second group | The mean glycemic value was lower for IDeg-100 than Gla-300 | - | • IDeg-100 and Gla-300 have comparable glucose-stabilizing effects in individuals with T1DM. • The TAR (>180 mg/dL [10.0 mmol/L]) and TBR (<70 mg/dL [3.9 mmol/L]) were shorter and longer, respectively, for IDeg-100 than Gla-300 |
| Rea et al. (2019) [21] | Multicenter, phase 4 | 123 | 28 weeks | • Switching from BD basal insulin to OD • Gla-300 |
No significant reduction in HbA1c from baseline to week-24 (P = 0.873) | Reduction from run-into the last 4 weeks on treatment in the proportion of individuals with at least one hypoglycemic event (P = 0.025), as well as decreased numbers of hypoglycemic events/pt-year of any type, symptomatic, and confirmed ≤ 70 mg/dL (P = 0.036, 0.007, and 0.049, respectively). | • Switching from a BD basal insulin to an OD Gla-300 brought significant reduction in SMBG and 8-point SMBG and a reduced incidence of hypoglycemia and increased satisfaction. |
| Mathieu et al. (2019) [22] | Prospective, multicenter, open-label, phase 4 OPTIMIZE study | 94 | 28 weeks | • Switching from Basal Insulin BD to Gla-300 OD plus prandial insulin | -0.27 (0.15, 0.40) | No change in hypoglycemic event rates (103.1 to 110.3 per pt/year) | • Better overall treatment satisfaction and improvement in HbA1c, without increase in the rate of hypoglycemia, was achieved on switching from BD to OD Gla-300 plus prandial insulin. |
| Pettus et al. (2019) [23] | Multicenter, randomized controlled phase 4 study | 638 | 16 weeks | • Gla-300 • Gla-100 |
0.59% (SD, 0.77) reduction; 0.62% (SD, 0.73) reduction |
Nocturnal hypoglycemia: 70.8% vs. 68.3% | • TIR and glycemic variability were similar for Gla-300 and Gla-100 recipients in the mITT population of relatively well-controlled individuals with T1DM. • In individuals with HbA1c <7.5%, Gla-300 provided improvements in TIR compared with Gla-100. |
| Bergenstal et al. (2017) [24] | Exploratory, open-label, parallel-group, two-period crossover study |
59 | 16 weeks | • Gla-100 • Gla-300 |
-0.22% -0.44% |
Confirmed: 9.0 vs. 4.0 events/participants-year | • Less increase in CGM-based glucose levels, smoother average 24-h glucose profiles, and reduced nocturnal hypoglycemia were observed with Gla-300. |
| Heise et al. (2017) [25] | Double-blind, crossover, randomized study | 71 | 8 months | • IDeg-100 • Gla-300 |
- | 35.6% individuals (50 episodes) 25.9% individuals (30 episodes) |
• IDeg-100 has a more stable glucose lowering effect allowing for tighter glycemic control and a lower risk of hypoglycemia. |
| Matsuhisa et al. (2016) [26] | Multicenter, open-label, phase III study (EDITION JP 1) |
243 | 6 months | • Gla-100 • Gla-300 |
0.43% 0.30% |
Severe: 9.9% vs. 5.7% | • Less hypoglycemia was observed with Gla-300 than with Gla-100, particularly during the night, while glycemic control did not differ. |
| Jinnouchi et al. (2015) [27] | Exploratory, single-center, 2-sequence, 2-period, open-label crossover study | 20 | 8.4 weeks | • Gla-300 followed by Gla-100 and • Gla-100 followed by Gla-300 |
- | Gla-300 vs. Gla-100 Participants experiencing ≥1 hypoglycemic event of any kind (85% vs. 100%) Total number of hypoglycemic events (126 vs. 192) Nocturnal hypoglycemia events (6 vs. 20) |
• No between-treatment difference was observed in glucose variability with Gla-300 vs. Gla-100 (Measured by CGM). • A trend for less hypoglycemia with Gla-300, particularly at night, vs. Gla-100. |
| Terauchi Y, et al. (2016) [28] | Multicenter, open-label, phase III study | 241 | 6 months | • Gla-100 • Gla-300 |
7.52% 7.56% |
Nocturnal confirmed (≤3.9 mmol/l) or severe hypoglycemia risk was 38% lower with Gla-300 vs. Gla-100 | • Japanese people with T1DM using basal insulin plus OAD(s) experienced less hypoglycemia with Gla-300 than with Gla-100, while glycemic control did not differ. |
| Home et al. (2015) [29] | Multicenter, randomized, four-arm, parallel-group, phase IIIa study (EDITION 4) |
549 | 6 months | • Gla-100 • Gla-300 |
-0.44% -0.42% |
72.5 events/patients-year 78.4 events/patients-year |
• Gla-300 has a lower risk of hypoglycemia after transfer from other insulins, regardless of injection time, and causes less weight gain. |
| Real-world evidence | |||||||
| Oriot P, et al. (2018) [30] | A retrospective, observational, single-center study |
116 | 11 months | • Switched from once- or twice-daily injections of Gla-100 to once-daily of Gla-300 | HbA1c reduction (from 8.0 ± 1.0% to 7.9 ± 1.0%; P = 0.03). | Nocturnal hypoglycemic events: [22.2% vs. 12.2%; relative risk 0.46 (95% CI 0.30 – 0.68); P < 0.0001]; Individuals with nocturnal hypoglycemia per period [30% vs. 16%; relative risk 0.53 (95% CI 0.31–0.86); P < 0.01]. |
• Gla-300 was more effective than Gla-100 in lowering the hypoglycemia risk post 12-months of treatment in people with T1DM |
| Alarcon PP, et al. (2018) [31] | Descriptive real-world study | 247 | 12-months | • Switch from Gla-100 to Gla-300 | No changes in HbA1c, but the proportion of people with HbA1c <7.5% increased at 6-months (33.5 vs. 40.5%; P < 0.05) and remained stable during one-year of follow-up. | Significant reduction in hypoglycemic events after one year of treatment in individuals with previous hypoglycemic events. | • Gla-300 is a potential basal insulin alternative to treat T1DM, improving metabolic control in individuals with HbA1c levels >7.5 and decreasing hypoglycemic events in individuals with history of hypoglycemia without increasing body weight. |
Abbreviations: BD, twice-daily; CGM, continuous glucose monitoring; Gla-100, glargine 100 U/mL; Gla-300, glargine 300 U/mL; HbA1c, glycated hemoglobin; OADs, oral antidiabetic agents; OD, once-daily; SMBG, self-monitoring of blood glucose; TAR, time above range; TBR, time below range; TIR, time-in-range; T1DM, type 1 diabetes mellitus.