Efficacy and safety of lixisenatide in the treatment of Type 2 diabetes mellitus: a review of Phase III clinical data

Figures & data

Figure 1. Changes in HbA_1c levels following treatment with lixisenatide either as monotherapy (GetGoal-Mono) or in combination with oral antidiabetic drugs (GetGoal-M, GetGoal-F1, GetGoal-S, GetGoal-P).

Standard error values are given where available.

*p < 0.0001 versus placebo.

am: Morning administration; ext.: Extension; MET: Metformin; PIOG: Pioglitazone; pm: Evening administration; q.d.: Once daily; 1s: One-step dosing; 2s: Two-step dosing; SU: Sulfonylurea.

Data taken from [46–50].

Figure 2. Changes in fasting plasma glucose following treatment with lixisenatide either as monotherapy (GetGoal-Mono) or in combination with oral antidiabetic drugs (GetGoal-M, GetGoal-F1, GetGoal-S, GetGoal-P).

Standard error values are given where available.

*p < 0.01 versus placebo; **p < 0.001 versus placebo; ***p < 0.0001 versus placebo.

1s: One-step dosing; 2s: Two-step dosing; am: Morning administration; ext.: Extension; FPG: Fasting plasma glucose; MET: Metformin; PIOG: Pioglitazone; pm: Evening administration; q.d.: Once daily; SU: Sulfonylurea.

Data taken from [46–50].

Figure 3. Changes in 2-h postprandial glucose following treatment with lixisenatide either as monotherapy (GetGoal-Mono) or in combination with oral antidiabetic drugs (GetGoal-M, GetGoal-F1, GetGoal-S).

2-h PPG indicates plasma glucose levels taken 2 h after a standardized meal, at baseline and follow-up. Mean changes from baseline are presented with last observations carried forward. Standard error values are given where available.

*p < 0.0001 versus placebo.

1s: One-step dosing; 2s: Two-step dosing; am: Morning administration; ext.: Extension; MET: Metformin; NR: Not reported; PPG: Postprandial glucose; q.d.: Once daily;

SU: Sulfonylurea.

Data taken from [46–49].

Figure 4. Changes in HbA_1c levels following treatment with lixisenatide in combination with insulin (GetGoal-L, GetGoal-L Asia, GetGoal-Duo 1).

Standard error values are given where available.

*p < 0.0001 versus placebo; **p < 0.001 versus placebo. ^†Following 12-week run-in period.

MET: Metformin; q.d.: Once daily; SU: Sulfonylurea.

Data taken from [52–54].

Figure 5. Changes in 2-h postprandial glucose following treatment with lixisenatide in combination with insulin (GetGoal-L, GetGoal-L Asia, GetGoal-Duo 1).

Two-hour PPG indicates plasma glucose levels taken 2 h after a standardized meal, at baseline and follow-up. Mean changes from baseline are presented with last observations carried forward. Standard error values are given where available.

*p < 0.0001 versus placebo.

MET: Metformin; PPG: Postprandial glucose; q.d.: Once daily; SU: Sulfonylurea.

Data taken from [52–54].

Table 1.  Summary of studies from the Phase III GetGoal clinical program that are included in this review.

Study (year)	Trial	Patients (n)	Patient demographics	Concomitant therapy	Treatment arms	Duration (weeks)^†	Study primary end point	Ref.
Fonseca et al. (2012)	GetGoal-Mono	361	52% male; mean age: 53–54 years; 73% Caucasian; 22% Asian		LIXI 20 µg q.d., one-step LIXI 20 µg q.d., two-step PBO	12	Mean change in HbA1c level (%) from baseline	[46]
Pinget et al. (2012)	GetGoal-P	484	52% male; mean age: 55–56 years; 84% Caucasian	Pioglitazone ± metformin	LIXI 20 µg q.d. PBO	24	Mean change in HbA1c level (%) from baseline	[50]
Bolli (2011)	GetGoal-F1	482	45% male; mean age: 55–58 years; 91% Caucasian	Metformin	LIXI 20 µg q.d., one-step LIXI 20 µg q.d., two-step PBO	24	Mean change in HbA1c level (%) from baseline	[47]
Aronson et al. (2011)	GetGoal-M	680	43% male; mean age: 55 years; 89% Caucasian	Metformin	LIXI 20 µg q.d., two-step, morning LIXI 20 µg q.d., two-step, evening PBO	24	Mean change in HbA1c level (%) from baseline	[48]
Ratner et al. (2011)	GetGoal-S	859	50% male; mean age: 57 years; 52% Caucasian; 45% Asian	Sulfonylurea ± metformin	LIXI 20 µg q.d., two-step PBO	24	Mean change in HbA1c level (%) from baseline	[49]
Rosenstock et al. (2011)	GetGoal-X	634	53% male; mean age: 57 years; 93% Caucasian	Metformin	LIXI 20 µg q.d., two-step, morning Exenatide 10 µg b.i.d.	24	Mean change in HbA1c level (%) from baseline (noninferiority)	[51]
Riddle et al. (2012)	GetGoal-L	493	46% male; mean age: 57–58 years; 77% Caucasian	Basal insulin ± metformin	LIXI 20 µg q.d., morning PBO	24	Mean change in HbA1c level (%) from baseline	[52]
Seino et al. (2012)	GetGoal-L Asia	311	48% male; mean age: 58 years; 100% Asian	Basal insulin ± sulfonylurea	LIXI 20 µg q.d., two-step, morning PBO	24	Mean change in HbA1c level (%) from baseline	[53]
Rosenstock et al. (2012)	GetGoal-Duo	446	50% male; mean age: 56 years; ethnicity not reported	Titrated insulin glargine; metformin ± thiazolidinedione	LIXI 20 µg q.d., morning PBO	24	Mean change in HbA1c level (%) from randomization	[54]

^†Duration over which primary end point was assessed.

b.i.d.: Twice daily; LIXI: Lixisenatide; PBO: Placebo; q.d.: Once daily.

Table 2. Incidence of hypoglycemic events in the GetGoal program (presented as percentage of patients experiencing events).

Study (year)	Concomitant therapy	Treatment arm	Any symptomatic hypoglycemia with BG <3.3 mmol/l (%)	Severe symptomatic hypoglycemia (%)	Ref.
GetGoal-Mono (2012)		LIXI 20 µg q.d., one-step	0.8	0	46]
		LIXI 20 µg q.d., two-step	2.5	0
		PBO	1.6	0
GetGoal-P (2012)	Pioglitazone ± metformin	LIXI 20 µg q.d.	3.4	0	[50]
		PBO	1.2	0
GetGoal-F1 (2011)	Metformin	LIXI 20 µg q.d., one-step	1.9	0	[47]
		LIXI 20 µg q.d., two-step	1.9	0
		PBO	0	0
GetGoal-M (2011)	Metformin	LIXI 20 µg q.d., two-step, morning	2.4	0	[48]
		LIXI 20 µg q.d., two-step, evening	5.1	0
		PBO	0.6	0
GetGoal-S (2011)	Sulfonylurea ± metformin	LIXI 20 µg q.d., two-step	12.2	0.2	[49]
		PBO	8.4	0
GetGoal-X (2011)	Metformin	LIXI 20 µg q.d., two-step, morning	2.2*	0	[51]
		Exenatide 10 µg b.i.d.	6.3	0
GetGoal-L (2012)	Basal insulin ± metformin	LIXI 20 µg q.d., morning	26.5	1.2	[52]
		PBO	21.0	0
GetGoal-L Asia (2012)	Basal insulin ± sulfonylurea	LIXI 20 µg q.d., two-step, morning	38.3	0	[53]
		PBO	20.4	0
GetGoal-Duo 1 (2012)	Titrated insulin glargine; metformin ± thiazolidinedione	LIXI 20 µg q.d., morning	20.2	0.4	[54]
		PBO	11.7	0

*p < 0.05 vs exenatide.

BG: Blood glucose; b.i.d.: Twice daily; LIXI: Lixisenatide; PBO: Placebo; q.d.: Once daily.

Table 3.  Incidence of gastrointestinal adverse events in the GetGoal program (presented as percentage of patients experiencing events).

Study (year)	OAD therapy	Treatment arm	Any GI event (%)	Nausea (%)	Diarrhea (%)	Vomiting (%)	Ref.
GetGoal-Mono (2012)		LIXI 20 µg q.d., one-step	31.9	20.2	NR	6.7	[46]
		LIXI 20 µg q.d., two-step	32.5	24.2	NR	7.5
		PBO	13.9	4.1	NR	0
GetGoal-P (2012)	Pioglitazone ± metformin	LIXI 20 µg q.d.	36.5	23.5	7.1	6.8	[50]
		PBO	28.6	10.6	10.6	3.7
GetGoal-F1 (2011)	Metformin	LIXI 20 µg q.d., one-step	41.6	26.1	6.2	11.8	[47]
		LIXI 20 µg q.d., two-step	47.2	35.4	12.4	15.5
		PBO	21.9	4.4	8.8	0
GetGoal-M (2011)	Metformin	LIXI 20 µg q.d., two-step, morning	36.5	22.7	10.6	9.4	[48]
		LIXI 20 µg q.d., two-step, evening	41.2	21.2	10.6	13.3
		PBO	25.9	7.6	8.8	2.9
GetGoal-S (2011)	Sulfonylurea ± metformin	LIXI 20 µg q.d., two-step	40.9	25.3	8.9	8.7	[49]
		PBO	20.0	7.0	6.7	3.5
GetGoal-X (2011)	Metformin	LIXI 20 µg q.d., two-step, morning	43.1	24.5*	10.4	10.1	[51]
		Exenatide 10 µg b.i.d.	50.6	35.1	13.3	13.3
GetGoal-L (2012)	Basal insulin ± metformin	LIXI 20 µg q.d., morning	40.2	26.2	7.3	8.2	[52]
		PBO	20.4	8.4	5.4	0.6
GetGoal-L Asia (2012)	Basal insulin ± sulfonylurea	LIXI 20 µg q.d., two-step, morning	61.0	39.6	6.5	18.2	[53]
		PBO	14.6	4.5	2.5	1.9
GetGoal-Duo 1 (2012)	Titrated insulin glargine; metformin ± thiazolidinedione	LIXI 20 µg q.d., morning	39.9	27.4	6.7	9.4	[54]
		PBO	16.1	4.9	3.1	1.3

*p < 0.05 vs exenatide.

b.i.d.: Twice daily; GI: Gastrointestinal; LIXI: Lixisenatide; NR: Not reported; OAD: Oral antidiabetic agent; PBO: Placebo; q.d.: Once daily.

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