Clinical trial NCT00975286: 24-week Treatment With Lixisenatide in Type 2 Diabetes Insufficiently Controlled With Metformin and Insulin Glargine
Official title: A Randomized, Placebo-controlled, 2-arm Parallel-group, Multicenter Study With a 24-week Double-blind Treatment Period Assessing the Efficacy and Safety of Lixisenatide in Patients With Type 2 Diabetes Insufficiently Controlled With Insulin Glargine and Metformin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2009-09-11
Enrollment: 446
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the benefits and risks of lixisenatide (AVE0010), in comparison to placebo, as an add-on treatment to insulin glargine and metformin with or without thiazolidinediones (TZDs), over a period of 24 weeks of treatment.

The primary objective is to assess the effects of lixisenatide in comparison to placebo, when added to insulin glargine and metformin, on glycemic control in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 24.

The secondary objectives are to assess the effects of lixisenatide on the percentage of patients reaching HbA1c less than (\<) 7 percent (%) and less than or equal to (\<=) 6.5%, plasma glucose (fasting, postprandial during a standardized meal challenge test, 7-point self monitored profiles), body weight, insulin glargine doses, to evaluate safety and tolerability (including anti-lixisenatide antibody assessment), and to assess the impact on treatment satisfaction using the Diabetes Treatment Satisfaction Questionnaire (state) (DTSQs) in the participating countries where it is validated.

Detailed description: The study comprises 3 periods:

* An up to 14-week screening period, which includes an up to 2-week screening phase and a 12-week run-in phase with introduction and titration of insulin glargine on top of metformin +/-TZDs.
* At the end of the run-in phase, patients whose HbA1c (centralized assay) is greater than or equal to (\>=) 7% and less than or equal to (\<=) 9% and whose mean fasting self-monitored plasma glucose (SMPG) calculated from the self measurements for the 7 days prior to Visit 12 (Week -1) is \<=140 milligram per deciliter (mg/dL) (7.8 millimole per liter \[mmol/L\]), would enter a 24-week double-blind randomized treatment period comparing lixisenatide to placebo (on top of insulin glargine + metformin +/- TZDs).
* A 3-day safety follow up period.

Maximum duration is of 39 weeks +/- 7 days.

Eligibility criteria: Inclusion criteria:

- Type 2 diabetes mellitus, diagnosed for at least 1 year before screening visit, insufficiently controlled with insulin glargine and metformin

Exclusion criteria:

* HbA1c \<7% or greater than (\>)10% at screening
* At the time of screening age \< legal age of majority
* Pregnant or breastfeeding women or women of childbearing potential with no effective contraceptive method
* Type 1 diabetes mellitus
* Metformin not at a stable dose of at least 1.5 gram per day for at least 3 months prior to the screening visit
* Use of oral or injectable antidiabetic or hypoglycemic agents other than metformin, sulfonylurea (SU) and TZDs (for example, alpha glucosidase inhibitor, other glucagon like peptide-1 \[GLP-1\] receptor agonists, dipeptidyl peptidase-IV \[DPP-IV\] inhibitors, insulin etc.) within 3 months prior to the time of screening, use of weight loss drugs if not at a stable dose for at least 3 months prior to the screening visit
* History of hypoglycemia unawareness
* Body Mass Index (BMI) less than or equal to (\<=) 20 kilogram per square meter (kg/m\^2)
* History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease, personal or family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (for example, multiple endocrine neoplasia syndromes)
* History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening
* Hemoglobinopathy or hemolytic anemia, blood or plasma products transfusion within 3 months prior to the time of screening
* Within the last 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization
* Known history of drug or alcohol abuse within 6 months prior to the time of screening
* Any clinically significant abnormality identified on physical examination, laboratory tests, electrocardiogram or vital signs at the time of screening that in the judgment of the Investigator or any sub investigator precludes safe completion of the study or constrains efficacy assessment such as active malignant tumor or other major systemic diseases, presence of clinically significant diabetic retinopathy or presence of macular edema likely to require laser treatment within the study period
* Uncontrolled or inadequately controlled hypertension at the time of screening with a resting systolic or diastolic blood pressure \>180 millimeter of mercury (mmHg) or \>110 mmHg, respectively
* Laboratory findings at the time of screening: amylase and/or lipase, alanine aminotransferase \>3 times upper limit of the normal (ULN) laboratory range; total bilirubin: \>1.5 times ULN (except in case of Gilbert's syndrome); hemoglobin \<11 gram/deciliter and/or neutrophils \<1500 per cubic millimeter (mm\^3) and/or platelets \<100 000/mm\^3; positive test for Hepatitis B surface antigen and/or Hepatitis C antibody, positive serum pregnancy test in females of childbearing potential; and calcitonin \>=20 picogram per milliliter (pg/mL) (5.9 picomole per milliliter \[pmol/L\])
* Patients who are considered by the Investigator or any sub investigator as inappropriate for this study for any reason (for example, impossibility to meet specific protocol requirements, such as scheduled visits, being able to do self-injections, likelihood of requiring treatment during the screening phase and treatment phase with drugs not permitted by the clinical study protocol, patient being investigator or any sub investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol etc.)
* Use of systemic glucocorticoids (excluding topical application or inhaled forms) for one week or more within 3 months prior to the time of screening
* Use of any investigational drug within 3 months prior to screening
* Renal impairment defined with serum creatinine \> 1.4 mg/dL in women and \> 1.5 mg/dL in men
* History of hypersensitivity to insulin glargine or to any of the excipients
* Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to): gastroparesis, unstable (that is, worsening) and not controlled (that is, prolonged nausea and vomiting) gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening
* Any previous treatment with lixisenatide (for example, participation in a previous study with lixisenatide)
* Allergic reaction to any GLP-1 receptor agonist in the past (for example, exenatide, liraglutide) or to metacresol
* Additional exclusion criteria during or at the end of the run-in phase before randomization: informed consent withdrawal (patient who was not willing to continue or failed to return), mean fasting SMPG calculated from the self-measurements for the 7 days prior to Visit 12 (Week -1) was \>140 mg/dL (7.8 mmol/L) and HbA1c measured at Visit 12 (Week -1) is \<7% or \>9%, amylase and/or lipase \> 3 times the ULN at Visit 12 (Week -1), patients with fasting plasma glucose (FPG) above the threshold value described for rescue (that is, FPG \>240 mg/dL \[13.3 mmol/L\]), patients with any adverse event, which, by the judgment of the Investigator precludes the inclusion in the double-blind randomized treatment phase, and lack of compliance to protocol or to insulin glargine treatment during the run-in phase

Primary outcomes:
measure: Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Glucose Excursion at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Average 7-Point Self Monitored Plasma Glucose (SMPG) Profile at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Body Weight at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Average Insulin Glargine Daily Dose at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24
timeFrame: Week 24
measure: Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24
timeFrame: Week 24
measure: Percentage of Patients Requiring Rescue Therapy During the Double-blind Period
timeFrame: Baseline up to Week 24
measure: Change From Baseline in Treatment Satisfaction Score (Sum of Items 1, 4, 5, 6, 7 and 8 of DTSQ) at Week 24
timeFrame: Baseline, Week 24
Other outcomes:
measure: Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24
timeFrame: Baseline, Week 24
measure: Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia
timeFrame: First dose of study drug up to 3 days after the last dose administration
Locations:
city: Mesa
country: United States
facility: Sanofi-Aventis Investigational Site Number 840223
state: Arizona
city: Hot Springs
country: United States
facility: Sanofi-Aventis Investigational Site Number 840206
state: Arkansas
city: Little Rock
country: United States
facility: Sanofi-Aventis Investigational Site Number 840201
state: Arkansas
city: Mountain Home
country: United States
facility: Sanofi-Aventis Investigational Site Number 840212
state: Arkansas
city: Concord
country: United States
facility: Sanofi-Aventis Investigational Site Number 840215
state: California
city: Greenbrae
country: United States
facility: Sanofi-Aventis Investigational Site Number 840214
state: California
city: Orlando
country: United States
facility: Sanofi-Aventis Investigational Site Number 840221
state: Florida
city: Baton Rouge
country: United States
facility: Sanofi-Aventis Investigational Site Number 840211
state: Louisiana
city: Hyattsville
country: United States
facility: Sanofi-Aventis Investigational Site Number 840230
state: Maryland
city: Rockville
country: United States
facility: Sanofi-Aventis Investigational Site Number 840209
state: Maryland
city: Brighton
country: United States
facility: Sanofi-Aventis Investigational Site Number 840219
state: Michigan
city: Sea Girt
country: United States
facility: Sanofi-Aventis Investigational Site Number 840231
state: New Jersey
city: Fargo
country: United States
facility: Sanofi-Aventis Investigational Site Number 840208
state: North Dakota
city: Mentor
country: United States
facility: Sanofi-Aventis Investigational Site Number 840225
state: Ohio
city: Portland
country: United States
facility: Sanofi-Aventis Investigational Site Number 840222
state: Oregon
city: Philadelphia
country: United States
facility: Sanofi-Aventis Investigational Site Number 840202
state: Pennsylvania
city: Bristol
country: United States
facility: Sanofi-Aventis Investigational Site Number 840229
state: Tennessee
city: Germantown
country: United States
facility: Sanofi-Aventis Investigational Site Number 840205
state: Tennessee
city: Dallas
country: United States
facility: Sanofi-Aventis Investigational Site Number 840210
state: Texas
city: Houston
country: United States
facility: Sanofi-Aventis Investigational Site Number 840217
state: Texas
city: Houston
country: United States
facility: Sanofi-Aventis Investigational Site Number 840228
state: Texas
city: Plano
country: United States
facility: Sanofi-Aventis Investigational Site Number 840213
state: Texas
city: Norfolk
country: United States
facility: Sanofi-Aventis Investigational Site Number 840227
state: Virginia
city: Buenos Aires
country: Argentina
facility: Sanofi-Aventis Investigational Site Number 032204
city: Capital Federal
country: Argentina
facility: Sanofi-Aventis Investigational Site Number 032205
city: Capital Federal
country: Argentina
facility: Sanofi-Aventis Investigational Site Number 032201
city: Capital Federal
country: Argentina
facility: Sanofi-Aventis Investigational Site Number 032209
city: Corrientes
country: Argentina
facility: Sanofi-Aventis Investigational Site Number 032211
city: Parana
country: Argentina
facility: Sanofi-Aventis Investigational Site Number 032202
city: Rosario
country: Argentina
facility: Sanofi-Aventis Investigational Site Number 032203
city: Belem
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 076207
city: Brasilia
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 076202
city: Porto Alegre
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 076205
city: Sao Paulo
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 076204
city: Brampton
country: Canada
facility: Sanofi-Aventis Investigational Site Number 124219
city: Chatham
country: Canada
facility: Sanofi-Aventis Investigational Site Number 124213
city: Chilliwack
country: Canada
facility: Sanofi-Aventis Investigational Site Number 124208
city: Etobicoke
country: Canada
facility: Sanofi-Aventis Investigational Site Number 124215
city: Quebec
country: Canada
facility: Sanofi-Aventis Investigational Site Number 124205
city: Red Deer
country: Canada
facility: Sanofi-Aventis Investigational Site Number 124202
city: Thornhill
country: Canada
facility: Sanofi-Aventis Investigational Site Number 124218
city: Toronto
country: Canada
facility: Sanofi-Aventis Investigational Site Number 124201
city: Toronto
country: Canada
facility: Sanofi-Aventis Investigational Site Number 124207
city: Victoria
country: Canada
facility: Sanofi-Aventis Investigational Site Number 124209
city: Winnipeg
country: Canada
facility: Sanofi-Aventis Investigational Site Number 124217
city: Santiago
country: Chile
facility: Sanofi-Aventis Investigational Site Number 152202
city: Santiago
country: Chile
facility: Sanofi-Aventis Investigational Site Number 152203
city: Santiago
country: Chile
facility: Sanofi-Aventis Investigational Site Number 152206
city: Santiago
country: Chile
facility: Sanofi-Aventis Investigational Site Number 152204
city: Santiago
country: Chile
facility: Sanofi-Aventis Investigational Site Number 152205
city: Santiago
country: Chile
facility: Sanofi-Aventis Investigational Site Number 152201
city: Barranquilla
country: Colombia
facility: Sanofi-Aventis Investigational Site Number 170204
city: Bogota
country: Colombia
facility: Sanofi-Aventis Investigational Site Number 170201
city: Bogota
country: Colombia
facility: Sanofi-Aventis Investigational Site Number 170202
city: Hradec Kralove
country: Czech Republic
facility: Sanofi-Aventis Investigational Site Number 203202
city: Praha 5
country: Czech Republic
facility: Sanofi-Aventis Investigational Site Number 203204
city: Frederiksberg
country: Denmark
facility: Sanofi-Aventis Investigational Site Number 208202
city: København Nv
country: Denmark
facility: Sanofi-Aventis Investigational Site Number 208201
city: Slagelse
country: Denmark
facility: Sanofi-Aventis Investigational Site Number 208205
city: Pärnu
country: Estonia
facility: Sanofi-Aventis Investigational Site Number 233201
city: Tallinn
country: Estonia
facility: Sanofi-Aventis Investigational Site Number 233203
city: Tartu
country: Estonia
facility: Sanofi-Aventis Investigational Site Number 233204
city: Viljandimaa
country: Estonia
facility: Sanofi-Aventis Investigational Site Number 233202
city: Amiens Cedex 1
country: France
facility: Sanofi-Aventis Investigational Site Number 250204
city: La Rochelle Cedex
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facility: Sanofi-Aventis Investigational Site Number 250206
city: Le Creusot
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facility: Sanofi-Aventis Investigational Site Number 250203
city: Nantes
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city: Pierre Benite
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city: Dresden
country: Germany
facility: Sanofi-Aventis Investigational Site Number 276201
city: Mainz
country: Germany
facility: Sanofi-Aventis Investigational Site Number 276202
city: St. Ingbert-Oberwürzbach
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facility: Sanofi-Aventis Investigational Site Number 276204
city: Balatonfüred
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facility: Sanofi-Aventis Investigational Site Number 348205
city: Budapest
country: Hungary
facility: Sanofi-Aventis Investigational Site Number 348202
city: Budapest
country: Hungary
facility: Sanofi-Aventis Investigational Site Number 348207
city: Debrecen
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facility: Sanofi-Aventis Investigational Site Number 348204
city: Gyula
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facility: Sanofi-Aventis Investigational Site Number 348206
city: Szeged
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facility: Sanofi-Aventis Investigational Site Number 348203
city: Zalaegerszeg
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facility: Sanofi-Aventis Investigational Site Number 348201
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country: India
facility: Sanofi-Aventis Investigational Site Number 356210
city: Bangalore
country: India
facility: Sanofi-Aventis Investigational Site Number 356206
city: Bangalore
country: India
facility: Sanofi-Aventis Investigational Site Number 356204
city: Bangalore
country: India
facility: Sanofi-Aventis Investigational Site Number 356202
city: Belgaum
country: India
facility: Sanofi-Aventis Investigational Site Number 356201
city: Chennai
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facility: Sanofi-Aventis Investigational Site Number 356205
city: Indore
country: India
facility: Sanofi-Aventis Investigational Site Number 356208
city: Karnal
country: India
facility: Sanofi-Aventis Investigational Site Number 356203
city: Kochi
country: India
facility: Sanofi-Aventis Investigational Site Number 356207
city: Nagpur
country: India
facility: Sanofi-Aventis Investigational Site Number 356209
city: Haifa
country: Israel
facility: Sanofi-Aventis Investigational Site Number 376202
city: Holon
country: Israel
facility: Sanofi-Aventis Investigational Site Number 376201
city: Kfar Saba
country: Israel
facility: Sanofi-Aventis Investigational Site Number 376204
city: Tel Hashomer
country: Israel
facility: Sanofi-Aventis Investigational Site Number 376203
city: Milano
country: Italy
facility: Sanofi-Aventis Investigational Site Number 380201
city: Perugia
country: Italy
facility: Sanofi-Aventis Investigational Site Number 380202
city: Kelantan
country: Malaysia
facility: Sanofi-Aventis Investigational Site Number 458203
city: Kuala Lumpur
country: Malaysia
facility: Sanofi-Aventis Investigational Site Number 458202
city: Cuernavaca
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 484201
city: Durango
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 484204
city: Guadalajara
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 484203
city: México City
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 484206
city: Tlalnepantla
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 484205
city: Amsterdam
country: Netherlands
facility: Sanofi-Aventis Investigational Site Number 528203
city: Groningen
country: Netherlands
facility: Sanofi-Aventis Investigational Site Number 528202
city: Zwijndrecht
country: Netherlands
facility: Sanofi-Aventis Investigational Site Number 528204
city: Krakow
country: Poland
facility: Sanofi-Aventis Investigational Site Number 616202
city: Lubin
country: Poland
facility: Sanofi-Aventis Investigational Site Number 616208
city: Plock
country: Poland
facility: Sanofi-Aventis Investigational Site Number 616206
city: Pulawy
country: Poland
facility: Sanofi-Aventis Investigational Site Number 616207
city: Sopot
country: Poland
facility: Sanofi-Aventis Investigational Site Number 616205
city: Szczecin
country: Poland
facility: Sanofi-Aventis Investigational Site Number 616201
city: Zabrze
country: Poland
facility: Sanofi-Aventis Investigational Site Number 616203
city: Ponce
country: Puerto Rico
facility: Sanofi-Aventis Investigational Site Number 840226
city: San Juan
country: Puerto Rico
facility: Sanofi-Aventis Investigational Site Number 840216
city: Brasov
country: Romania
facility: Sanofi-Aventis Investigational Site Number 642204
city: Bucharest
country: Romania
facility: Sanofi-Aventis Investigational Site Number 642208
city: Deva
country: Romania
facility: Sanofi-Aventis Investigational Site Number 642205
city: Iasi
country: Romania
facility: Sanofi-Aventis Investigational Site Number 642203
city: Oradea
country: Romania
facility: Sanofi-Aventis Investigational Site Number 642202
city: Targu Mures
country: Romania
facility: Sanofi-Aventis Investigational Site Number 642206
city: Timisoara
country: Romania
facility: Sanofi-Aventis Investigational Site Number 642207
city: Timisoara
country: Romania
facility: Sanofi-Aventis Investigational Site Number 642201
city: Saratov
country: Russian Federation
facility: Sanofi-Aventis Investigational Site Number 643203
city: St. Petersburg
country: Russian Federation
facility: Sanofi-Aventis Investigational Site Number 643202
city: Cape Town
country: South Africa
facility: Sanofi-Aventis Investigational Site Number 710202
city: Durban
country: South Africa
facility: Sanofi-Aventis Investigational Site Number 710201
city: Pretoria
country: South Africa
facility: Sanofi-Aventis Investigational Site Number 710203
city: Göteborg
country: Sweden
facility: Sanofi-Aventis Investigational Site Number 752204
city: Härnösand
country: Sweden
facility: Sanofi-Aventis Investigational Site Number 752203
city: Luleå
country: Sweden
facility: Sanofi-Aventis Investigational Site Number 752205
city: Malmö
country: Sweden
facility: Sanofi-Aventis Investigational Site Number 752202
city: Stockholm
country: Sweden
facility: Sanofi-Aventis Investigational Site Number 752201
city: Changhua
country: Taiwan
facility: Sanofi-Aventis Investigational Site Number 158204
city: Taichung R.O.C.
country: Taiwan
facility: Sanofi-Aventis Investigational Site Number 158201
city: Taichung
country: Taiwan
facility: Sanofi-Aventis Investigational Site Number 158203
city: Tainan Hsien
country: Taiwan
facility: Sanofi-Aventis Investigational Site Number 158202
city: Chernivtsi
country: Ukraine
facility: Sanofi-Aventis Investigational Site Number 804203
city: Kiev
country: Ukraine
facility: Sanofi-Aventis Investigational Site Number 804201
city: Kyiv
country: Ukraine
facility: Sanofi-Aventis Investigational Site Number 804205
city: Kyiv
country: Ukraine
facility: Sanofi-Aventis Investigational Site Number 804202
city: Vinnytsya
country: Ukraine
facility: Sanofi-Aventis Investigational Site Number 804204
Study officials:
affiliation: Sanofi
name: Clinical Study Operations
role: STUDY_DIRECTOR
References:
citation: Riddle MC, Forst T, Aronson R, Sauque-Reyna L, Souhami E, Silvestre L, Ping L, Rosenstock J. Adding once-daily lixisenatide for type 2 diabetes inadequately controlled with newly initiated and continuously titrated basal insulin glargine: a 24-week, randomized, placebo-controlled study (GetGoal-Duo 1). Diabetes Care. 2013 Sep;36(9):2497-503. doi: 10.2337/dc12-2462. Epub 2013 Apr 5.
citation: Davidson JA, Stager W, Paranjape S, Berria R, Leiter LA. Achieving postprandial glucose control with lixisenatide improves glycemic control in patients with type 2 diabetes on basal insulin: a post-hoc analysis of pooled data. Clin Diabetes Endocrinol. 2020 Jan 14;6:2. doi: 10.1186/s40842-019-0088-5. eCollection 2020.
citation: Rosenstock J, Handelsman Y, Vidal J, Ampudia Blasco FJ, Giorgino F, Liu M, Perfetti R, Meier JJ. Propensity-score-matched comparative analyses of simultaneously administered fixed-ratio insulin glargine 100 U and lixisenatide (iGlarLixi) vs sequential administration of insulin glargine and lixisenatide in uncontrolled type 2 diabetes. Diabetes Obes Metab. 2018 Dec;20(12):2821-2829. doi: 10.1111/dom.13462. Epub 2018 Aug 13.
citation: Charbonnel B, Bertolini M, Tinahones FJ, Domingo MP, Davies M. Lixisenatide plus basal insulin in patients with type 2 diabetes mellitus: a meta-analysis. J Diabetes Complications. 2014 Nov-Dec;28(6):880-6. doi: 10.1016/j.jdiacomp.2014.07.007. Epub 2014 Jul 18.
citation: Riddle MC, Aronson R, Home P, Marre M, Niemoeller E, Miossec P, Ping L, Ye J, Rosenstock J. Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: a 24-week, randomized, placebo-controlled comparison (GetGoal-L). Diabetes Care. 2013 Sep;36(9):2489-96. doi: 10.2337/dc12-2454. Epub 2013 Apr 29.