Insulin degludec/liraglutide (IDegLira) for the treatment of type 2 diabetes

Figures & data

Figure 1. Amino acid structure of native human GLP-1 and liraglutide [16].

Ala: alanine; Asp: aspartic acid; Cys: cysteine; GLP-1: Glucagon-like peptide 1; Gln: glutamine; Glu: glutamic acid; Gly: glycine; Ile: isoleucine; Leu: leucine; Lys: lysine; Phe: phenylalamine; Ser: serine; Thr: threonine; Trp: tryptopan; Tyr: tyrocine; Val: valine.

Figure 2. Structure (A) and mechanism of protraction (B) of insulin degludec [34].

Glu: glutamic acid; Lys: lysine.

Figure 3. The IDegLira clinical trial program: DUAL.

Ext: Extension trial; IAsp: Insulin aspart; IDegLira: Insulin degludec/liraglutide combination; IGlar: Insulin glargine; GLP-1: Glucagon-like peptide-1; OAD: Oral antidiabetic drug; SU: Sulfonylurea. Accessed 26 June 2015. www.clinicaltrials.gov.

Table 1. Key results from IDegLira Phase 3a and 3b trials [12,54,55–57].

	DUAL I [12]		DUAL II [53]	DUAL III [55]	DUAL IV [56]	DUAL V [57]
	IDegLira vs IDeg	IDegLira vs liraglutide	IDegLira vs IDeg	IDegLira vs unchanged GLP-1RA	IDegLira vs placebo	IDegLira vs insulin glargine
HbA1c change^†, ETD, %-points	–0.47 (–0.58 to –0.36), p < 0.0001 (noninferior)	–0.64 (–0.75 to –0.53), p < 0.0001 (superior)	–1.1 (–1.3 to –0.8), p < 0.0001 (superior)	–0.94 (–1.11 to –0.78), p < 0.001 (superior)	–1.02%, p < 0.001	–0.59 (–0.74 to –0.45), p < 0.001
Fasting plasma glucose change^†, ETD, mmol/l	–0.17 (–0.41 to 0.07), NS	–1.76 (–2.00 to –1.53), p < 0.0001	–0.73 (–0.19 to –0.27), p = 0.0019	–2.64 (–3.03 to –2.25), p < 0.001	–2.30, p < 0.001	–0.01 (–0.35 to –0.33), NS
Mean of postprandial plasma glucose increment across all main meals, ETD, mmol/l	–0.45 (–0.63 to –0.28), p < 0.0001	0.06 (–0.11 to 0.23), NS	–0.4 (–0.7 to –0.0) p = 0.0260	N/A	N/A	N/A
Weight change^†, ETD, kg	–2.22 (–2.64 to –1.80), p < 0.0001	+2.44 (2.02–2.86), p < 0.0001	–2.5 (–3.2 to –1.8), p < 0.0001	2.89 (2.17–3.62], p < 0.001	N/A	–3.2 (–3.77 to –2.64), p < 0.001
Confirmed hypoglycemia^‡, rate ratio	0.68 (0.53 to 0.87), p = 0.0023	7.61 (5.17 to 11.21), p < 0.0001	0.66 (0.39 to 1.13), NS	25.4 (10.6 to 60.5), p < 0.001	3.74, p < 0.001	0.43 (0.30 to 0.61), p < 0.001
Nocturnal confirmed hypoglycemia^§, rate ratio	N/A	N/A	0.81 (0.35 to 1.90), NS	N/A	N/A	0.17 (0.10 to 0.31), p < 0.001
Daily insulin dose^¶, ETD, U	–14.90 (–17.14 to 12.66), p < 0.0001	N/A	0.02 NS	N/A	N/A	41 dose steps vs 66 U p < 0.001

Values in square brackets indicate 95% CIs.

^† Change from baseline to end of trial (week 26).

^‡ Confirmed with plasma glucose <3.1 mmol/l.

^§Nocturnal confirmed hypoglycemia, plasma glucose <3.1 mmol/l occurring 00:01–05:59 inclusive.

^¶ At week 26.

ETD: Estimated treatment difference; IDegLira: Insulin degludec/liraglutide; N/A: Not applicable/available; NS: Not significant.

Table 2. Key safety information from IDegLira Phase 3a trials [12,54].

	DUAL I [12]			DUAL II [53]
	IDegLira	IDeg	Liraglutide	IDegLira	IDeg
	(n = 825)	(n = 412)	(n = 412)	(n = 199)	(n = 199)
Adverse events, n (%)	521 (63)	248 (60)	299 (73)	115 (57.8)	122 (61.3)
Serious adverse events, n (%)	19 (2)	8 (2)	14 (3)	7 (3.5)	11 (5.5)
Nausea, n (%)	73 (9)	15 (4)	81 (20)	13 (6.5)	7 (3.5)

Based on the safety analysis sets.

IDegLira: Insulin degludec/liraglutide; N: Number of subjects; %: Percentages of subjects.

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