Glycated haemoglobin reduction and fixed ratio combinations of analogue basal insulin and glucagon-like peptide-1 receptor agonists: A systematic review

Table 1 Study characteristics

Ref.	Study design	Patient population	Intervention	Comparator	Efficacy endpoint	Efficacy outcome time-point
Lingvay et al[25]	Multinational, multicentre, 26-wk, randomised, open-label, 2-group, treat-to-target trial	Adults with type 2 diabetes	Insulin degludec/liraglutide	Insulin glargine U100	Baseline HbA1c level was 8.4% for the degludec/liraglutide group and 8.2% for the glargine group. HbA1c level reduction was greater with degludec/liraglutide vs glargine [-1.81% for the degludec/liraglutide group vs -1.13% for the glargine group; estimated treatment difference, -0.59% (95%CI: -0.74 to -0.45)], meeting criteria for noninferiority (P < 0.001) and meeting criteria for statistical superiority (P < 0.001)	26-wk
Rosenstock et al[26]	Randomised, open-label, parallel group, multicentre	Adults with type 2 diabetes	iGlarLixi	Insulin Glargine U100	Mean HbA1c was reduced from 8.0% at baseline to 6.3% and 6.5% with LixiLan and Gla-100, respectively, establishing statistical noninferiority and superiority of LixiLan [least-squared mean (95%CI) difference: -0.17% (-0.31, -0.04) (-1.9 mmol/mol, -3.4, -0.4); P = 0.01]	24-wk
Rosenstock et al[28]	Randomised, parallel, open label, 3-arm-treatment	Adults with type 2 diabetes	iGlarLixi	Insulin glargine U100; Lixisenatide	Greater reductions in HbA1c from baseline (8.1%) were achieved with iGlarLixi compared with iGlar and Lixi (-1.6%, -1.3%, -0.9%, respectively), reaching mean final HbA1c levels of 6.5% for iGlarLixi vs 6.8% and 7.3% for iGlar and Lixi, respectively (both P < 0.0001)	30-wk

CI: Confidence interval; HbA1c: Haemoglobin A1c.

Table 2 Patient arm characteristics

		Baseline characteristics
		Gender	Ethnic origin											OAD at screening
Ref.	Arms	M (%)/F (%)	White (%)	Black (%)	Asian (%)	Other (%)	Age (yr)	Bodyweight	BMI (kg/ m2)	Duration of Diabetes (yr)	HbA1 (%)	Hb (mmol/mol)	FPG (mmol/L)	Metformin	Metformin plus pioglitazone	Sulphonylurea	Other
Lingvay et al[25]	Degludec/liraglutide (n = 278)	51.4/48.6	94.2	2.2	3.2	0.4	58.4	88.3	31.7	11.64	8.4	NA	8.9	NA	NA	NA	NA
	Glargine (n = 279)	49.1/50.9	95.0	1.8	3.2	0.0	59.1	87.3	31.7	11.33	8.2	NA	8.9	NA	NA	NA	NA
Rosenstock et al[26]	LixiLan (n = 161)	49.7/50.3	98.1	NA	NA	NA	56.9	90.1	32.2	6.3	8.1	64	9.8	Yes	NA	NA	NA
	Gla-100 (n = 162)	52.5/47.5	98.8	NA	NA	NA	56.6	91.6	32.0	7.1	8.0	64	9.5	Yes	NA	NA	NA
Rosenstock et al[28]	iGlarLixi (n = 469)	47.3/52.7	88.9	7.0	1.7	2.3	58.2	NA	31.6	8.9	8.1	65	9.9	Yes	NA	55.2	Glinide, Sodium glucose co-transporter inhibitor, dipeptidyl dipeptidase 4 inhibitor
	iGlar (n = 467)	50.7/49.3	90.1	7.1	1.5	1.3	58.3	NA	31.7	8.7	8.1	65	9.8	Yes	NA	53.3
	Lixi (n = 234)	56.8/43.2	92.3	5.1	1.3	1.3	58.7	NA	32.0	8.9	8.1	65	9.8	Yes	NA	52.6
	All (n = 1170)	50.6/49.4	90.1	6.7	1.5	1.7	58.4	NA	31.7	8.8	8.1	65	9.8	Yes	NA	53.9

NA: Not available; BMI: Body mass index; M: Male; F: Female; Hb: Haemoglobin; FPG: Fasting plasma glucose; OAD: Oral antihyperglycaemic drug.

Table 3 Study bias assessment

Ref.	Selection bias: Random sequence generation	Selection bias: Allocation concealment	Performance bias: Blinding of participants	Performance bias: Blinding of personnel/care providers	Detection bias: Blinding of outcome assessor	Attrition bias: Incomplete outcome data	Reporting bias: Selective outcome reporting	Intention-to-treat-analysis	Selection bias: Group similarity at baseline	Performance bias: Co-interventions	Performance bias: Compliance	Detection bias: Timing of outcome assessments	Additional bias	Overall quality
Lingvay et al[25]	L	H	H	H	L	L	L	L	L	L	L	L	L	Moderate
Rosenstock et al[26]	L	H	H	H	L	L	L	L	L	L	L	L	L	Moderate
Rosenstock et al[28]	L	H	H	H	L	L	L	L	L	L	L	L	L	Moderate

H: High risk of bias; M: Moderate risk of bias; L: Low risk of bias.