Clinical trial NCT00751114: Evaluation of Insulin Glargine Versus Sitagliptin in Insulin-naive Patients
Official title: Superiority Study of Insulin Glargine Over Sitagliptin in Insulin-naïve Patients With Type 2 Diabetes Treated With Metformin and Not Adequately Controlled
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2008-09-11
Enrollment: 515
Sex: ALL
Minimum age (years): 35
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective was to demonstrate the superiority of insulin glargine over sitagliptin in reducing Glycosylated Hemoglobin A1c (HbA1c) from baseline to the end of the treatment period.

Secondary objective was to assess the effect of insulin glargine in comparison with sitagliptin on:

* HbA1c level
* Fasting Plasma Glucose (FPG)
* 7-point plasma glucose (PG) profiles
* Percentage of patients with HbA1c \<7% and \<6.5%

Safety objectives consisted of:

* Hypoglycemia occurrence
* Body weight
* Overall safety


Eligibility criteria: Inclusion Criteria:

* With type 2 diabetes diagnosed for at least 6 months,
* Not previously treated with insulin,
* On metformin for at least 3 months and a stable minimal dose of 1 g/day for at least 2 months
* HbA1c ≥ 7 and \< 11 %,
* Body Mass Index (BMI) between 25 and 45 kg/m² inclusively,
* Ability and willingness to perform plasma glucose (PG) monitoring using the Sponsor-provided PG meter and to complete the patient diary,
* Signed informed consent obtained prior any study procedures,
* Willingness and ability to comply with the study protocol.

Exclusion Criteria:

* Treatment with oral antidiabetic drugs other than metformin within the last 3 months,
* Previous treatment with the combination of metformin + sulfonylurea for more than 1 year,
* Previous treatment with Glucagon Like Peptide-1 (GLP-1) agonists or DiPeptidyl Peptidase (DPP) IV inhibitors,
* FPG (assessed by central laboratory measurement) ≥ 280 mg/dL (15.4 mmol/L),
* Diabetes other than type 2 diabetes (e.g. secondary to pancreatic disorders, drug or chemical agents intake...),
* Pregnant or lactating women (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraception method),
* In-patient care,
* Active proliferative retinopathy, as defined by a photocoagulation or vitrectomy occurrence in the 6 months prior to visit 1, or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgical treatment during the study (an optic fundus examination should have been performed within the 2 years prior to study entry),
* Impaired renal function: serum creatinine ≥ 1.5 mg/dL (≥ 133µmol/L) or ≥ 1.4 mg/dL (≥ 124 µmol/L) in men and women, respectively,
* History of sensitivity to the study drugs or to drugs with a similar chemical structure,
* Impaired hepatic function: alanine aminotransferase (ALT), aspartate aminotransferase (AST) \> 3 x upper limit of normal range,
* Treatment with systemic corticosteroids within the 3 months prior to study entry or likelihood of requiring treatment during the study that are not permitted during the study (exception: in case of chronic adrenal insufficiency, systemic glucosteroids are accepted only if the disease is stable and the treatment dose stable for at least 3 months before study entry),
* Alcohol or drug abuse within the last year,
* Night shift worker,
* Presence of any condition (medical, psychological, social or geographical), current or anticipated that the investigator feels would compromise the patient's safety or limit the patient successful participation in the study,
* Treatment with weight loss medications (e.g. sibutramine, orlistat, rimonabant) within the last 3 months,
* Participation in another clinical trial within the month prior to visit 1,
* History of pancreatitis.

Primary outcomes:
measure: HbA1c: Change From Baseline to Study Endpoint
timeFrame: baseline (week 0), study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14
Secondary outcomes:
measure: HbA1c Response Rate: Percentage of Patients Who Reach the Target of HbA1c < 7% at Study Endpoint
timeFrame: study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14
measure: HbA1c Response Rate: Percentage of Patients Who Reach the Target of HbA1c < 6.5% at Study Endpoint
timeFrame: study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14
measure: Self-monitored Fasting Plasma Glucose (SMFPG) Mean : Change From Baseline to Study Endpoint
timeFrame: baseline (week 0), study endpoint: visit 14 (week 24) or visit 12 (week 16) or visit 11 (week 12) or visit 8 (week 6) depending on last available value
measure: 7-point Plasma Glucose Profile: Change From Baseline to Study Endpoint
timeFrame: baseline (week 0), study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14
measure: Insulin Dose in the Insulin Glargine Group
timeFrame: visit 4 (week 2), visit 8 (week 6), visit 11 (week 12), visit 12 (week 16), visit 14 (week 24), first dose received defined as first available value, study endpoint defined as last available value
measure: Lipid Profile: Change From Baseline to Study Endpoint
timeFrame: baseline (week 0), study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14
measure: Change in Body Weight From Baseline to Study Endpoint
timeFrame: baseline (week 0), study endpoint: visit 14 (week 24) or visit 12 (week 16) or visit 11 (week 12) or visit 8 (week 6) depending on last available value
measure: Number of Patients With at Least One Episode of Symptomatic Hypoglycemia
timeFrame: During the treatment phase (24 weeks) plus 7 days after last dose
measure: Number of Patients With at Least One Episode of Severe Symptomatic Hypoglycemia
timeFrame: During the treatment phase (24 weeks) plus 7 days after last dose
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis Administrative Office
state: New Jersey
city: Vienna
country: Austria
facility: Sanofi-Aventis Administrative Office
city: Sao Paulo
country: Brazil
facility: Sanofi-Aventis Administrative Office
city: Bogota
country: Colombia
facility: Sanofi-Aventis Administrative Office
city: Cairo
country: Egypt
facility: Sanofi-Aventis Administrative Office
city: Kallithea
country: Greece
facility: Sanofi-Aventis Administrative Office
city: Hong Kong
country: Hong Kong
facility: Sanofi-Aventis Administrative Office
city: Mumbai
country: India
facility: Sanofi-Aventis Administrative Office
city: Natanya
country: Israel
facility: Sanofi-Aventis Administrative Office
city: Seoul
country: Korea, Republic of
facility: Sanofi-Aventis Administrative Office
city: Beirut
country: Lebanon
facility: Sanofi-Aventis Administrative Office
city: Col. Coyoacan
country: Mexico
facility: Sanofi-Aventis Administrative Office
city: Gouda
country: Netherlands
facility: Sanofi-Aventis Administrative Office
city: Porto Salvo
country: Portugal
facility: Sanofi-Aventis Administrative Office
city: Barcelona
country: Spain
facility: Sanofi-Aventis Administrative Office
city: Istanbul
country: Turkey
facility: Sanofi-Aventis Administrative Office
city: Guildford Surrey
country: United Kingdom
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Aschner P, Chan J, Owens DR, Picard S, Wang E, Dain MP, Pilorget V, Echtay A, Fonseca V; EASIE investigators. Insulin glargine versus sitagliptin in insulin-naive patients with type 2 diabetes mellitus uncontrolled on metformin (EASIE): a multicentre, randomised open-label trial. Lancet. 2012 Jun 16;379(9833):2262-9. doi: 10.1016/S0140-6736(12)60439-5. Epub 2012 Jun 9.
citation: Chan JC, Aschner P, Owens DR, Picard S, Vincent M, Dain MP, Pilorget V, Loizeau V, Echtay A, Fonseca V. Triple combination of insulin glargine, sitagliptin and metformin in type 2 diabetes: the EASIE post-hoc analysis and extension trial. J Diabetes Complications. 2015 Jan-Feb;29(1):134-41. doi: 10.1016/j.jdiacomp.2014.08.007. Epub 2014 Aug 27.