TABLE 1.

Overview of Published Clinical Trials of Novel Insulin Formulations

StudyDesignTreatmentEnrolled PopulationOutcomes
Gla-300
EDITION 1 (34) (n = 807)Phase 3, MC, OL, 24-week, randomizedGla-300 QD evening + mealtime insulin vs. Gla-100 QD evening + mealtime insulinType 2 diabetes patients insufficiently controlled with basal + mealtime insulin, aged 60 years, duration of diabetes 15.8 years, A1C 8.15%, BMI 36.6 kg/m2Change in A1C: LS mean change −0.83% (SE 0.06) in both groups
Nocturnal hypoglycemia*: 44.6 and 57.5% for Gla-300 and Gla-100, respectively; RR 0.78 (95% CI 0.68–0.89)
Change in body weight: +0.9 kg for both treatment groups
EDITION 1 extension (35) (n = 714)24-week extension to 1 yearGla-300 QD evening + mealtime insulin vs. Gla-100 QD evening + mealtime insulinType 2 diabetes patients insufficiently controlled with basal + mealtime insulin, aged 60 years, duration of diabetes 15.8 years, A1C 8.15%, BMI 36.6 kg/m2Endpoint A1C: LS mean difference −0.17% (95% CI −0.30 to −0.05) for Gla-300 vs. Gla-100
Nocturnal hypoglycemia*: 54.5 and 64.7% for Gla-300 and Gla-100, respectively; RR 0.84 (95% CI 0.75–0.94)
Change in body weight: +1.17 and +1.40 kg for Gla-300 and Gla-100, respectively; LS mean difference −0.23 kg (95% CI −0.74 to 0.27)
EDITION 2 (36) (n = 811)Phase 3, MC, OL, 24-week, randomizedGla-300 QD evening vs. Gla-100 QD eveningAdult type 2 diabetes patients insufficiently controlled with basal insulin + OADs, aged 58.2 years, duration of diabetes 12.6 years, A1C 8.24%, BMI 34.8 kg/m2Change in A1C: LS mean change −0.57% (SE 0.09) and −0.56% (SE 0.09) for Gla-300 and Gla-100, respectively
LS mean difference −0.01% (95% CI −0.14 to 0.12)
Nocturnal hypoglycemia*: 28.3 and 39.9% for Gla-300 and Gla-100, respectively; RR 0.71 (95% CI 0.58–0.86)
Change in body weight: 0.08 and 0.66 kg for Gla-300 and Gla-100, respectively (P = 0.015)
EDITION 2 extension (37) (n = 811)24-week extension to 1 yearGla-300 QD evening vs. Gla-100 QD eveningAdult type 2 diabetes patients insufficiently controlled with basal insulin plus OADs, aged 58.2 years, duration of diabetes 12.6 years, A1C 8.24%, BMI 34.8 kg/m2Change in A1C: improvements maintained at 12 months
Nocturnal hypoglycemia*: incidence RR 0.84 (95% CI 0.71–0.99) for Gla-300 vs. Gla-100
Change in body weight: +0.42 and +1.14 kg for Gla-300 and Gla-100, respectively (P = 0.0091)
EDITION 3 (38) (n = 878)Phase 3, MC, OL, 24-week, randomizedGla-300 QD evening vs. Gla-100 QD eveningAdult insulin-naive type 2 diabetes patients, aged 57.7 years, duration of diabetes 9.8 years, A1C 8.5%, BMI 33.0 kg/m2Reduction in A1C: LS mean change −1.42% (SE 0.05) and −1.46% (SE 0.05) for Gla-300 and Gla-100, respectively
Nocturnal hypoglycemia*: RR 0.76 (95% CI 0.59–0.99)
Change in body weight: +0.4 and +0.7 kg for Gla-300 and Gla-100, respectively
EDITION 4 (39) (n = 549)Phase 3, MC, OL, 24-week, randomizedGla-300 QD morning or evening + mealtime insulin vs. Gla-100 QD morning or evening + mealtime insulinAdult type 1 diabetes patients, duration of diabetes 21.0 years, A1C 8.12%, BMI 27.6 kg/m2Change in A1C: LS mean change −0.40% (SE 0.05) and −0.44% (SE 0.05) for Gla-300 and Gla-100, respectively
Nocturnal hypoglycemia*: 8.0 and 8.9 events per patient-year for Gla-300 and Gla-100, respectively; rate ratio 0.90 (95% CI 0.71–1.14)
Change in body weight: difference −0.56 kg (95% CI −1.09 to −0.03; P = 0.037)
EDITION meta-analysis (40) (n = 2,496)Meta-analysis of three phase 3, MC, OL, 24-week, randomized trialsGla-300 QD evening vs. Gla-100 QD eveningHeterogeneous adult type 2 diabetes population, aged 58.6 years, duration of diabetes 12.6 years, A1C 8.3%, BMI 43.8 kg/m2Change in A1C: LS mean change −1.02% (SE 0.06) in both groups
Nocturnal hypoglycemia*: 30.0 and 39.8% for Gla-300 and Gla-100, respectively; RR 0.75 (95% CI 0.68–0.83)
Change in body weight: difference −0.26 kg (95% CI −0.55 to −0.01; P = 0.039)
Basal insulin peglispro
Rosenstock et al. (41) (n = 137)Phase 2, OL, CO, 8-week, randomizedBIL QD pre-breakfast + mealtime insulin vs. Gla-100 QD pre-breakfast + mealtime insulinType 1 diabetes patients, aged 38.2 years, duration of diabetes 18 years, A1C 7.75%, BMI 27.3 kg/m2Endpoint A1C: 7.07% (SE 0.07) and 7.22% (SE 0.08) for BIL and Gla-100, respectively
LS mean difference −0.18% (95% CI −0.25 to −0.10; P <0.001)
Endpoint daily mean BG: 144.2 and 151.7 mg/dL for BIL and Gla-100, respectively
LS mean difference −9.9 mg/dL (90% CI −14.6 to −5.2; P <0.001)
Nocturnal hypoglycemia*: 0.88 (SE 1.22) and 1.13 (SE 1.42) events/month for BIL and Gla-100, respectively (P = 0.012)
Change in body weight: −1.2 and +0.7 kg for BIL and Gla-100, respectively (P <0.001)
Bergenstal et al. (42) (n = 288)Phase 2, OL, 12-week, randomizedBIL QD pre-breakfast vs. Gla-100 QD pre-breakfastType 2 diabetes patients previously treated with insulin glargine or NPH insulin, aged 60 years, duration of diabetes 12 years, A1C 7.75%, BMI 32.1 kg/m2Endpoint A1C: 7.0% (SE 0.1) and 7.2% (SE 0.1) for BIL and Gla-100, respectively (P = 0.279)
Change in daily mean BG: −27.4 mg/dL (SE 2.5) and −19.6 mg/dL (SE 3.1) for BIL and Gla-100, respectively
LS mean difference −8.8 mg/dL (95% CI −15.0 to −2.7; P = 0.017)
Change in body weight: −0.6 (SE 0.2) and +0.3 kg (SE 0.2) for BIL and Gla-100, respectively
LS mean difference −0.8 kg (95% CI −1.3 to −0.4; P = 0.001)
Nocturnal hypoglycemia*: BIL had a 48% reduction in nocturnal hypoglycemia after adjusting for baseline hypoglycemia (P = 0.021)
Insulin degludec
BEGIN Basal-Bolus Type 2 (43) (n = 992)Phase 3, OL, MC, 52-week, treat-to-target, randomizedIDeg QD vs. Gla-100 QDType 2 diabetes patients previously treated with any insulin ± OADs, aged 58.9 years, duration of diabetes 13.5 years, A1C 8.3%, FPG 165.8 mg/dLChange in A1C: −1.1 and −1.2% for IDeg and Gla-100, respectively
Mean difference −0.08% (95% CI −0.05 to 0.21)
Nocturnal hypoglycemia*: 1.4 and 1.8 events/PYE for IDeg and Gla-100, respectively
Mean difference 0.75 (95% CI 0.58–0·99; P = 0.0399)
Overall confirmed hypoglycemia: 11.1 and 13.6 events/PYE for IDeg and Gla-100, respectively; estimated rate ratio 0.82 (95% CI 0.69–0.99; P = 0.0359)
BEGIN FLEX (44) (n = 687)Phase 3, OL, MC, 26-week, treat-to-target, randomizedIDeg QD flexible timing vs. IDeg QD evening meal vs. Gla-100 QDType 2 diabetes patient who were insulin-naive patients or previously treated with basal insulin ± OADs, aged 56.4 years, duration of diabetes 10.6 years, A1C 8.4%, BMI 29.6 kg/m2Change in A1C: −1.28, −1.07, and −1.26% for IDeg flexible, IDeg evening, and Gla-100, respectively
Treatment difference for IDeg flexible vs. Gla-100: 0.04% (95% CI −0.12 to 0.20)
Nocturnal hypoglycemia*: rate ratio 0.77 (95% CI 0.44–1.35; P = NS) for IDeg flexible vs. Gla-100
Change in body weight: +1.5 and +1.3 kg for IDeg flexible and Gla-100, respectively
Treatment difference +0.27 kg (95% CI –0.25 to 0.79; P = NS)
BEGIN: FLEX T1 (45) (n = 490)Phase 3, OL, MC, 26-week, treat-to-target, randomizedIDeg QD flexible timing vs. IDeg QD evening meal vs. Gla-100 QD + insulin aspart at mealtimesType 1 diabetes patients previously treated with basal-bolus therapy, aged 43.7 years, duration of diabetes 18.5 years, A1C 7.7%, weight 80.5 kgChange in A1C: −0.40, −0.41, and −0.58% for IDeg flexible, IDeg, and Gla-100, respectively
Nocturnal hypoglycemia*: 40% lower rate with IDeg flexible vs. Gla-100 (P = 0.001)
Change in body weight: +1.3 and +1.9 kg for IDeg flexible and Gla-100, respectively (P = NS)
BEGIN Once Long (46) (n = 1,030)Phase 3, OL, 52-week, randomizedIDeg QD + metformin vs. Gla-100 QD + metforminInsulin-naive type 2 diabetes patients, aged 59 years, duration of diabetes 9 years, A1C 8.2%, BMI 31.3 kg/m2Change in A1C: −1.06 and −1.19% for IDeg and Gla-100, respectively
Treatment difference 0.09% (95% CI –0.04 to 0.22)
Nocturnal hypoglycemia*: 0.25 and 0.39 events/PYE for IDeg and Gla-100, respectively (P = 0.038)
Change in body weight: +2.4 and +2.1 kg for IDeg and Gla-100, respectively (P = 0.28)
  • * Nocturnal hypoglycemia reported as confirmed or severe nocturnal hypoglycemia (≤3.9 mmol/L [≤70 mg/dL]).

  • BG, blood glucose; BIL, basal insulin peglispro LY2605541; CO, crossover; FPG, fasting plasma glucose; IDeg, insulin degludec; LS, least square; MC, multicenter; NS, not significant; OAD, oral antidiabetes drug; OL, open-label; PYE, patient-year of exposure; QD, once daily; RR, relative risk; SE, standard error.