Glargine-300: An updated literature review on randomized controlled trials and real-world studies

Table 1 Efficacy and safety of Gla-300 vs Gla-100 across the EDITION Phase 3 Clinical Trial Program

Study (ref.) / Registry	Diabetes type	Population	n (Gla-300 vs Gla-100)	Mean baseline A1C (%)	LS mean change in A1C from baseline to Month 6 (%)		TEAEs (%)		Serious TEAEs (%)
					Gla-300	Gla-100	Gla-300	Gla-100	Gla-300	Gla-100
EDITION 1[15], NCT01499082	T2DM	(1) Basal insulin users (≥ 42 U/d); (2) T2DM not adequately controlled; and (3) Basal insulin (evening) + mealtime insulin	807 (404 vs 403)	8.2	-0.83	-0.83	NA	NA	6.4	5.2
					Difference: -0.00%, (95%CI: -0.11 to 0.11)
EDITION 2[25], NCT01499095	T2DM	(1) Basal insulin users (≥ 42 U/d); and (2) Basal insulin (evening) + OADs	811 (404 vs 407)	8.2	-0.57	-0.56	58.8	50.7	3.7	3.7
					Difference: -0.01%, (95%CI: -0.14 to 0.12)
EDITION 3[26], NCT01676220	T2DM	Insulin-naïve (evening), uncontrolled using noninsulin therapy	878 (439 vs 439)	8.5	-1.42	-1.46	NA	NA	5.5	5.9
					Difference: 0.04%, (95%CI -0.09 to 0.17)
EDITION 4[27], NCT01683266	T1DM	Basal insulin (morning or evening) + mealtime insulin	549 (274 vs 275)	8.1	-0.42	-0.44	60.9	58.2	6.2	8.0
					Difference: 0.04%, (95%CI -0.10 to 0.19)
EDITION JP 1[28], NCT01689129	T1DM	(1) Japanese study; and (2) Basal insulin (evening) + mealtime insulin	243 (122 vs 121)	8.1	-0.30	-0.43	62.3	64.5	2.5	2.5
					Difference: 0.13%, (95%CI -0.03 to 0.29)
EDITION JP 2[29], NCT01689142	T2DM	(1) Japanese study; and (2) Basal insulin (evening) + OADs	240 (120 vs 120)	8.0	-0.45	-0.55	58.3	56.7	4.2	3.3
					Difference: 0.10%, (95%CI -0.08 to 0.27)

A1C: Glycated haemoglobin A_1C; CI: Confidence interval; Gla-100: Insulin glargine 100 U/mL; Gla-300: Insulin glargine 300 U/mL; OADs: Oral antidiabetic drugs; T1DM: Type 1 diabetes mellitus; T2DM: Type 2 diabetes mellitus; TEAE: Treatment emergent adverse event.

Table 2 Risk of hypoglycaemia for Gla-300 vs Gla-100 across the EDITION Phase 3 Clinical Trial Program (Safety population)

Study (ref.)		Confirmed [≤ 3.9 mmol/L (≤ 70 mg/dL)] or severe hypoglycaemia													At any time of the day
		Nocturnal							At any time of the day						Severe hypoglycaemia
		Baseline to Week 8		Week 9 to Month 6			Baseline to Month 6		Baseline to Week 8		Week 9 to Month 6		Baseline to Month 6		Baseline to Month 6
		Gla-300	Gla-100	Gla-300	Gla-100		Gla-300	Gla-100	Gla-300	Gla-100	Gla-300	Gla-100	Gla-300	Gla-100	Gla-300	Gla-100
EDITION 1[15]	Patients (%)	26.2	33.3	36.1	45.8		44.6	57.5	64.4	75.1	74.8	77.6	81.9	87.8	5.0	5.7
	RR (95%CI)	0.79 (0.64-0.98)		0.79 (0.67-0.93)			0.78 (0.68-0.89)		0.86 (0.78-0.94)		0.96 (0.89-1.04)		0.93 (0.88-0.99)		0.87 (0.48-1.55)
EDITION 2[25]	Patients (%)	13.2	24.6	21.6	27.9		28.3	39.9	47.1	60.1	59.3	65.0	70.0	77.3	1.0	1.2
	RR (95%CI)	0.53 (0.39-0.72)		0.77 (0.60-0.97)			0.71 (0.58-0.86)		0.78 (0.69-0.89)		0.91 (0.82-1.02)		0.90 (0.83-0.98)		NA
EDITION 3[26]	Patients (%)	7.4	10.0	15.4	17.1		17.9	23.5	24.1	29.2	39.8	46.3	46.2	52.5	0.9	0.9
	RR (95%CI)	0.74 (0.48-1.13)		0.90 (0.67-1.22)			0.76 (0.59-0.99)		0.83 (0.67-1.03)		0.86 (0.74-1.00)		0.88 (0.77-1.01)		NA
EDITION 4[27]	Patients (%)	46.7	57.1	59.1		55.6	68.6	70.2	88.3	90.2	82.1	84.0	93.1	93.5	6.6	9.5
	RR (95%CI)	0.82 (0.70-0.96)		1.06 (0.92-1.23)			0.98 (0.88-1.09)		0.98 (0.92-1.04)		0.98 (0.91-1.06)		1.00 (0.95-1.04)		0.71 (0.41-1.24)
EDITION JP 1[28]	Patients (%)	43.4	61.2	61.7	73.7		68.9	81.0	86.9	95.0	94.2	93.2	96.7	97.5	5.7	9.9
	RR (95%CI)	0.71 (0.56-0.91)		0.84 (0.70-1.00)			0.85 (0.73-0.99)		0.91 (0.84-0.99)		1.01 (0.95-1.08)		0.99 (0.95-1.04)		0.58 (0.24-1.42)
EDITION JP 2[29]	Patients (%)	13.3	16.7	25.4	43.7		28.3	45.8	37.5	55.0	60.2	72.3	65.0	76.7	2.5	1.7
	RR (95%CI)	0.83 (0.45-1.52)		0.58 (0.40-0.85)			0.62 (0.44-0.88)		0.69 (0.52-0.91)		0.84 (0.70-1.01)		0.86 (0.73-1.01)		1.25 (0.31-4.98)

Relative risk of experiencing ≥ 1 confirmed (blood glucose ≤ 70 mg/dL) or severe episode of hypoglycaemia. CI: Confidence interval; Gla-100: Insulin glargine 100 U/mL; Gla-300: Insulin glargine 300 U/mL; RR: Relative risk.