Author, year of publication	Study design	Participant inclusion criteria	Interventions	Key baseline characteristics	Duration	Primary objective/s
Bolli et al. [20]	Post-hoc, patient-level, pooled analysis of EDITION 2, 3 and JP2 trials	See appendix 1 for individual trial criteria	Gla-300 (n = 958) vs Gla-100 (n = 946)	Gla-300 vs Gla-100 (mean): Age 58 vs 58 years BMI 32.8 vs 32.8 kg/m2 HbA1c 8.3 vs 8.4 % Duration of diabetes 11.7 vs 11.4 years	6 months	Confirmed or severe hypoglycemia ≤3.9 mmol/L (≤70 mg/dL) examined across various nocturnal windows: The percentage of participants with at least one event was lower with Gla-300 than Gla-100 in all windows examined
Bonadonna et al. [21]	Patient-level, pooled analysis of EDITION 1, 2 and 3 trials	See appendix 1 for individual trial criteria	Gla-300 (n = 1247) vs Gla-100 (n = 1249)	Gla-300 vs Gla-100 (mean): Age: 59 vs 59 years BMI 34.7 vs 34.8 kg/m2 HbA1c 8.31 vs 8.32 % Duration of diabetes 12.7 vs 12.6 years	6 months	Annualized hypoglycemia rate confirmed ≤3.9 mmol/L (≤70 mg/dL) or severe as a function of HbA1c at month 6 using a negative binomial regression model: Participants on Gla-300 had a lower rate of hypoglycemia regardless of HbA1c at month 6
Diez-Fernandez et al. [22]	Systematic review and meta-analysis	RCTs comparing Gla-300 and Gla-100 reporting the rate ratio or number of events of nocturnal hypoglycemia and HbA1c levels in T1DM or T2DM	Gla-300 (n = 1998) vs Gla-100 (n = 1979)	Not reported—see appendix 1 for individual T2DM studies	Variable (up to 12 months)	Incidence rate ratio (RR) of nocturnal hypoglycemia: Nocturnal events ≤3.9 mmol/L (≤70 mg/dL) were lower with Gla-300 RR=0.81 (95% CI 0.69 to 0.95) and nocturnal events <3.0 mmol/L (<54 mg/dL) were lower with Gla-300 RR=0.75 (95% CI 0.63 to 0.91)
Zhou et al. [40]	Systematic review and meta-analysis	RCTs in T2DM comparing IDeg with insulin glargine (Gla-300 or Gla-100)	IDeg (n = 9619) vs Gla-300 or Gla-100 (n = 7075)	Refer to publication for individual trial breakdown of baseline characteristics	Variable (24–104 weeks)	Efficacy (HbA1c change from baseline) and safety of IDeg compared with pooled insulin glargine: Insulin glargine led to a greater mean reduction in HbA1c than IDeg mean difference 0.07% (95% CI 0.01 to 0.13) P= 0.019
Bonadonna et al. [41]	Post-hoc, patient-level, meta-analysis of EDITION 1 and 2	See appendix 1 for individual trial criteria	Gla-300 (n = 808) vs Gla (n = 810)	Gla-300 vs Gla-100 (range): Age 57 to 61 years BMI 35.2 to 36.2 kg/m2 HbA1c 8.1 to 8.3 % Duration of disease 10.6 to 17.8 years Dose of basal insulin 0.63 to 0.68 U/kg/day	6 months	Assess the impact of duration of prior basal insulin therapy outcomes with Gla-300 vs Gla-100 for 6 months: HbA1c change from baseline to month 6 was comparable groups with a lower risk of ≥1 confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemic events, at night or any time (24 h) with Gla-300, regardless of duration of prior basal insulin therapy
Ritzel et al. [65]	Patient-level pooled meta-analysis of EDITION 1, 2 and 3 at 12 months	See appendix 1 for individual trial criteria	Gla-300 (n = 1247) vs Gla-100 (n = 1249)	Gla-300 vs Gla-100 (mean): Age 59 vs 59 years BMI 34.7 vs 34.8 kg/m2 HbA1c 8.31 vs 8.32 % Duration of diabetes 12.7 vs 12.6 years	12 months	HbA1c change from baseline to month 12: LS mean change was −0.91% (SE 0.03) for Gla-300 and −0.080 (SE 0.03) for Gla-100 with treatment difference of −0.1% (95% CI −0.18 to −0.02) P= 0.0174
Twigg et al. [35]	Post-hoc, patient-level meta-analysis of EDITION 1, 2 and 3 at 6 months	See appendix 1 for individual trial criteria	Gla-300 (n = 1247) vs Gla-100 (n = 1249)	Gla-300 vs Gla-100 (mean): Age 59 vs 59 years BMI 34.7 vs 34.8 kg/m2 HbA1c 8.31 vs 8.32 % Duration of diabetes 12.7 vs 12.6 years	6 months	Association of patient baseline characteristics with glycemic control and hypoglycemia: HbA1c reductions were comparable between Gla-300 and Gla-100 regardless of patients baseline characteristics
Zhang et al. [38]	Systematic review and meta-analysis	RCTs comparing IDeg with Glargine in T1DM and T2DM with at least 16 weeks follow up	18 RCTs including 16791 participants on either IDeg or Gla-100	Refer to publication for individual trial breakdown of baseline characteristics	Variable (16–104 weeks)	Efficacy and hypoglycemia: No significant difference in HbA1c changes with estimated treatment difference of 0.03% (95% CI −0.00 to 0.06) P= 0.06 IDeg showed reduced hypoglycemia vs Gla-100 across multiple measures including severe hypoglycemia in T2DM (estimated RR 0.65 (95% CI 0.52 to 0.89) P= 0.005
Ritzel et al. [31]	Patient-level pooled meta-analysis of EDITION 1, 2 and 3 at 6 months	See appendix 1 for individual trial criteria	Gla-300 (n = 1247) vs Gla-100 (n = 1249)	Gla-300 vs Gla-100 (mean): Age 59 vs 59 years BMI 34.7 vs 34.8 kg/m2 HbA1c 8.31 vs 8.32 % Duration of diabetes 12.7 vs 12.6 years	6 months	HbA1c change from baseline to month 6: LS mean change was −1.02% (SE 0.03) for both groups with LS mean difference of 0.00% (95% CI −0.08 to 0.07)
Vora et al. [36]	Meta-analysis of BEGIN phase IIIa program	6 phase IIIa treat to target RCTs of the BEGIN program, including T1DM and T2DM	IDeg (n = 2848) vs Gla-100 (n = 1205)	See appendix 1 for individual trial baseline characteristics	Variable (26–52 weeks)	HbA1c change from baseline: IDeg non-inferior to Gla-100 in basal bolus regimens with an estimated mean difference of 0.08% (95% CI −0.05 to 0.21) and insulin naïve 0.08% (95% CI −0.01 to 0.16)
Monami and Mannucci [27]	Meta-analysis of IDeg	RCTs with a duration of at least 16 weeks comparing IDeg with other insulins +/− OADs and prandial insulin, including T1DM and T2DM	IDeg (n = 1517) vs comparators (Gla-100 n = 526; Biasp 30 n = 62)	Range across 5 RCTs: Age 43–59 years BMI 26.3–32.1 kg/m2 HbA1c 7.7–8.7 % Duration of diabetes 7–21 years	Variable (16–52 weeks)	Change in HbA1c and hypoglycemia outcomes: In T2DM: mean difference in HbA1c change between IDeg and Gla-100 was 0.02% (95% CI −0.10 to 0.14) P= 0.72; confirmed hypoglycemia was lower with IDeg OR 0.95 (95% CI 0.93 to 0.97) p <0.001 and no difference in nocturnal hypoglycemia OR 0.95 (95% CI 0.30 to 3.05) P= 0.94
Ratner et al. [29]	Pre-planned patient-level, meta-analysis of BEGIN phase IIIa program	7 phase IIIa treat to target RCTs of the BEGIN program, including T1DM and T2DM	IDeg (n = 2899) vs Gla-100 (n = 1431)	See appendix 1 for individual trial baseline characteristics	Variable (26–52 weeks)	Overall confirmed hypoglycemia <3.1 mmol/L (≤54 mg/dL): In T2DM: overall confirmed hypoglycaemia was lower with IDeg vs Gla-100, treatment difference ERR: 0.83 (95% CI 0.74 to 0.94)