Pharmacology, efficacy and safety of liraglutide in the management of type 2 diabetes

Figures & data

Table 1 Select efficacy outcomes from the Liraglutide Effects and Action in Diabetes (LEAD) trials

	Pts	Treatment		Treatment period (weeks)	HbA1C Change (%)	Achievement of HbA1C < 7% (%)	FPG change (mg/dL)	PPG change (mg/dL)	BW change (kg)
		Background	Intervention
LEAD-1^Citation42	1041	Glim 2–4 mg/day	Lir 0.6 mg/day	26	−0.6a	24a	−13.0a	−32.4a	+0.7b
			Lir 1.2 mg/day		−1.08a,b	35a,c	−28.3a,e	−45.0a,f	+0.3b
			Lir 1.8 mg/day		−1.13a,b	42a,d	−28.6a,e	−48.6a,g	−0.2b
			Ros 4 mg/day		−0.44a	22	−15.8	−32.4	+2.1
LEAD-2^Citation43	1091	Met 1 g twice daily	Placebo		+0.23	8	+18.2	−7.2f	−0.1
			Lir 0.6 mg/day	26	−0.7a	28.0i	−19.8a	−30.6j	−1.8b
			Lir 1.2 mg/day		−1.0a,h	35.3i	−28.8a	−41.4j	−2.6b,k
			Lir 1.8 mg/day		−1.0a,h	42.4i	−30.6a	−46.8j	−2.8b,k
			Glim 4 mg/day		−1.0a	36.3	−23.4a	−45.0j	+1.0
			Placebo		+0.1	10.8	+7.2	−10.8	−1.5
LEAD-3^Citation44	746	Diet/exercise	Lir 1.2 mg/day	52	−0.84l	42.8m	−15.1n	−30.8	−2.1b
		50% maximum dose of OAD monotherapy	Lir 1.8 mg/day		−1.14b	50.9b	−25.6b	−37.4o	−2.5b
			Glim 8 mg/day		−0.51	27.8	−5.2	−24.5	+1.1
LEAD-4^Citation45	533	Met 1 g twice daily	Lir 1.2 mg/day	26	−1.48a	57.5a	−40a	−47j	−1.0p
		Ros 8 mg/day	Lir 1.8 mg/day		−1.48a	53.7a	−44a	−49j	−2.0p
			Placebo		−0.54	28.1	−8	−14	+0.6
LEAD-5^Citation46	581	Met 1 g twice daily	Lir 1.8 mg/day	26	−1.33a,b	53.1a,q	−27.9a	−32.6a	−1.8a,b
		Glim 4 mg/day	Insulin glargine		−1.09	45.8	−32.2	−29.0	+1.6
			Placebo		−0.24	15.5	+9.5	−0.5	−0.4
LEAD-6^Citation41	464	Met	Lir 1.8 mg/day	26	−1.12b	54r	−29.0b	NRs	−3.2
		SU	Exen 10 μg bid		−0.79	43	−10.8	NR	−2.9

a Notes: P ≤ 0.0001 versus placebo;

b P < 0.0001 versus comparator;

c P = 0.0005 versus comparator;

d P < 0.0001 versus comparator;

e P <0.01 versus comparator;

f P = 0.043 versus comparator;

g P = 0.0022 versus comparator;

h noninferior to active comparator;

i P < 0.02 versus placebo;

j P < 0.001 versus placebo;

k P ≤ 0.01 versus placebo;

l P = 0.0014 versus comparator;

m P = 0.0007 versus comparator;

n P = 0.027 versus comparator;

o P = 0.0038 versus comparator;

P P < 0.05 versus placebo;

q P = 0.0139 versus comparator;

r P = 0.0015 versus comparator;

s Average reduction reported to be significantly greater for exenatide when compared with liraglutide.

Abbreviations: HbA_1c, hemoglobin HbA_1c; BW, body weight; Exen, exenatide; FPG, fasting plasma glucose; Glim, glimepiride; Lir, liraglutide; NR, not reported; OAD, oral antidiabetic drug; PPG, postprandial glucose; Pts, participants randomized; Ros, rosiglitazone; SU, sulfonylurea.

Table 2 Adverse drug event rates in Liraglutide Effects and Action in Diabetes (LEAD) trials

Study	Drug	Patients experiencing minor hypoglycemia (%)	Major hypoglycemic events (n)	Nausea (%)	Vomiting (%)	GI events (%)	Pancreatitis (number of subjects)	Pulse rate (bpm)	Liraglutide antibody formation (%)
LEAD-1^Citation42	Liraglutide 0.6 mg	5.2	0	NR	NR	NR	1	+2–4a b	9–13a
	Liraglutide 1.2 mg	9.2c,d	0	10.5	4.4	NR	0
	Liraglutide 1.8 mg	8.1e	1	NR	NR	NR	0
	Rosiglitazone 4 mg	4.3	0	NR	NR	NR	0	+1	NA
	Placebo	2.6	0	1.8	NR	NR	0	−1	NA
LEAD-2^Citation43	Liraglutide 0.6 mg	3a f	0	11	5–7a	35	0	+2–3a g	NR
	Liraglutide 1.2 mg			16		40	1		NR
	Liraglutide 1.8 mg			19		44	0		NR
	Glimepiride 4 mg	17	0	NR	1	17	1	+1	NA
	Placebo	3	0	NR	1	17	0	+1	NA
LEAD-3^Citation44	Liraglutide 1.2 mg	12f	0	27.5f	9.3	49	1	+3.2h	NR
	Liraglutide 1.8 mg	8f	0	29.3f	12.4	51	1	+1.6	NR
	Glimepiride 8 mg	24	0	8.5	3.6	26	0	+0.4	NA
LEAD-4^Citation45	Liraglutide 1.2 mg	9.0	0	29	7	45	0	+2	4.1
	Liraglutide 1.8 mg	7.9i	0	40	17	56	0	+3	6.7
	Placebo	5.1	0	NR	NR	19	0	−0.5	0
LEAD-5^Citation46	Liraglutide 1.8 mg	27.5	5	13.9	6.5	NR	0	+2.62	9.8
	Insulin glargine	28.9	0	1.3	0.4	NR	0	+0.08	NA
	Placebo	16.7	0	3.5	3.5	NR	0	+0.93	NA
LEAD-6^Citation41	Liraglutide 1.8 mg	26j	0	25.5	6.0	45.5	1	+3.28k	NR
	Exenatide 10 μg bid	34	2	28.0	9.9	42.7	0	+0.69	NA

a Notes: Reported composite for all liraglutide doses tested;

b P ≤ 0.002 versus placebo;

c P = 0.0024 versus comparator;

d P = 0.048 versus placebo;

e P = 0.0065 versus comparator;

f P < 0.001 versus comparator;

g P < 0.03 for 0.6 mg and 1.2 mg liraglutide groups versus comparator;

h P = 0.0027 versus comparator;

i P = 0.004 versus placebo;

j P = 0.0131 versus comparator;

k P = 0.0012 versus comparator.

Abbreviations: bid, twice daily; bpm, beats per minute; GI, gastrointestinal; NA, not applicable; NR, not reported.

Table 3 Clinical study withdrawal and serious adverse event rates in Liraglutide Effects and Action in Diabetes (LEAD) trials

Study	Drug	Discontinuation due to ADEa (%)	Serious adverse eventsb
LEAD-1^Citation42	Liraglutide 0.6 mg	20	3%
	Liraglutide 1.2 mg	34	4%
	Liraglutide 1.8 mg	43	5%
	Rosiglitazone 4 mg	19	3%
	Placebo	19	3%
LEAD-2^Citation43	Liraglutide 0.6 mg	32	NR
	Liraglutide 1.2 mg	52	NR
	Liraglutide 1.8 mg	57	NR
	Glimepiride 4 mg	23.5	NR
	Placebo	4	NR
LEAD-3^Citation44	Liraglutide 1.2 mg	28	16 subjects/18 events
	Liraglutide 1.8 mg	24	8 subjects/9 events
	Glimepiride 8 mg	16	13 subjects/17 events
LEAD-4^Citation45	Liraglutide 1.2 mg	44	8 subjects/8 events
	Liraglutide 1.8 mg	60	7 subjects/10 events
	Placebo	10.7	12 subjects/13 events
LEAD-5^Citation46	Liraglutide 1.8 mg	48	NR
	Insulin glargine	38.5	NR
	Placebo	5.5	NR
LEAD-6^Citation41	Liraglutide 1.8 mg	70	5.1%
	Exenatide 10 μg bid	69	2.6%

a Notes: Percentage of the total number of subject dropouts who withdrew due to an adverse drug event;

b Reported either as a percentage of study subjects or number of subjects and number of events.

Abbreviations: ADE, adverse drug event; NR, not reported.

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