Optimizing glycemic control: lixisenatide and basal insulin in combination therapy for the treatment of Type 2 diabetes mellitus

Figures & data

Figure 1. Glucagon-like peptide-1 fundamental mechanisms.

Figure 2. Chemical structure of lixisenatide and other GLP-1RAs.

Table 1. Summary of lixisenatide in Phase I and Phase II trials.

Trial	Phase	Patients (n)	Outcome	Ref.
Randomized, placebo-controlled, crossover clinical trial evaluating the interaction of lixisenatide (10 μg sc) on the absorption of concomitantly administered oral acetaminophen or oral contraceptive	I	40	Lixisenatide significantly reduced the absorption rate (lowering Cmax by 48–71% and prolonging Tmax by 2–3.5 h), but did not significantly affect the extent of absorption (AUC), indicating delayed gastric emptying	[53]
Lixisenatide vs placebo evaluating the dose-dependent effect on plasma glucose	I	28	Plasma glucose levels were reduced relative to placebo	[102]
Evaluation of efficacy of lixisenatide in T2DM patients as add on to metformin and/or SU therapy	II	64	Lixisenatide significantly reduced baseline plasma glucagon AUC and HbA1c levels compared with placebo	[102]
Evaluation of efficacy of lixisenatide in T2DM patients insufficiently controlled by metformin monotherapy	II	542	Lixisenatide vs placebo significantly and dose-dependently reduced mean HbA1c levels from baseline (−0.28 – [−0.57%]) with q.d. dosing and (−0.47 – [−0.69%]) with b.i.d. dosing	[54]

AUC: Area under the curve; C_max: Maximum concentration of drug; HbA_1c: Glycated hemoglobin; sc: Subcutaneous; SU: Sulfonylurea; T2DM: Type 2 diabetes mellitus; T_max: Amount of time that a drug is present at the maximum concentration.

Table 2. Summary of GetGoal Phase III clinical trial program.

Trial	Comparator	Participants	Duration(weeks)	Primary outcome	Secondary outcome	Status
GetGoal-Mono	LIXI vs PCB (1-step and 2-step titration)	361 adults previously untreated with antidiabetic agents	12	Change in HbA1c from baseline	Changes in body weight, FPG, 2-h PPG	Completed
GetGoal-F1	LIXI + MET vs PCB + MET (1-step and 2-step)	482 adults previously treated with MET	24	Change in HbA1c from baseline	Changes in body weight, FPG	Completed
GetGoal-S	LIXI + SU vs PCB + PCB	859 adults previously treated with SU	24	Change in HbA1c from baseline	Changes in body weight, FPG, 2-h PPG	Completed
GetGoal-L	LIXI + basal insulin vs PCB + basal insulin	495 adults previously treated with basal insulin	24	Change in HbA1c from baseline	Changes in body weight, FPG, change from baseline in insulin doses	Completed
GetGoal-P	LIXI + PIO vs PCB + PIO	484 adults previously treated with PIO	24	Change in HbA1c from baseline	Changes in body weight, FPG, fasting plasma insulin	Completed
GetGoal-X	LIXI + MET vs EXE + MET	634 adults previously treated with MET	24	Noninferiority in HbA1c reduction from baseline	Changes in body weight, FPG, quality of life	Completed
GetGoal-M	LIXI (morning or evening dose) + MET vs PCB + MET	680 adults previously treated with MET	24	Change in HbA1c from baseline	Changes in body weight, FPG, 2-h PPG	Completed
GetGoal-Mono Japan	Open-label LIXI (1-step and 2-step titration)	66 adults not treated with antidiabetes agents	52	Safety measures	Changes in HbA1c and FPG from baseline	Completed
GetGoal-L-Asia	LIXI + basal insulin vs PCB + basal insulin	311 adults previously treated with basal insulin ± SU	24	Change in HbA1c from baseline	Change from baseline in body weight, FPG, insulin doses	Completed
GetGoal-Duo-1	Insulin glargine + LIXI vs insulin glargine + PCB	446 adults with HbA1c 7–10% despite oral therapy	24 (with a 12-week insulin glargine run-in period)	Change in HbA1c from baseline	Changes in body weight, 2-h PPG	Completed
GetGoal-M-Asia	LIXI + MET ± SU vs PCB + MET ± SU	380 adults previously treated with MET or MET + SU	24	Change in HbA1c from baseline	Changes in body weight, FPG, 2-h PPG	Completed

EXE: Exenatide; FPG: Fasting plasma glucose; HbA_1c: Glycated hemoglobin; LIXI: Lixisenatide; MET: Metformin; PCB: Placebo; PIO: Pioglitazone; PPG: Postprandial plasma glucose; SU: Sulfonylurea.

Reproduced with permission from [29].

Drucker D. The biology of incretin hormones. Cell. Metab. 3, 153–165 (2006).

 PubMed Web of Science ®Google Scholar

Liu YH, Ruus P. Effect of the GLP-1 agonist AVE0010 on absorption of concomitant oral drugs. Annual Meeting American Diabetes Association, 69th Scientific Session. New Orleans, USA 2009 (Abstract 495).

 Google Scholar

Evaluate. Zealand Pharma Reports Successful Phase I/IIa Trial with ZP10 in Type 2 Diabetes Patients, 2002. www.evaluategroup.com/Universal/View.aspx?type=Story&id=199032 ( Accessed 20 June 2013)

 Google Scholar

Ratner RE, Rosenstock J, Boka G. A dose-finding study of the new GLP-1 AVE0010 in type 2 diabetes insufficiently controlled with metformin. Annual Meeting of the American Diabetes Association: Abstract 433-P (2008).

 Google Scholar

Barnett A. Lixisenatide: evidence for its potential use in the treatment of type 2 diabetes. Core Evid. 6, 67–79 (2011).

 PubMedGoogle Scholar