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Evaluation of Insulin Glargine Versus Sitagliptin in Insulin-naive Patients

Phase 4
Completed
Conditions
Diabetes Mellitus, Type 2
Interventions
Registration Number
NCT00751114
Lead Sponsor
Sanofi
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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
515
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Insulin GlargineInsulin GlargineAdministered once a day in the evening at dinner or at bedtime with a starting dose 0.2 U/kg. Then, the doses were to be individually adjusted, following a titration algorithm, to reach the FPG target: 70mg/dL\<FPG≤100mg/dL (3.9mmol/L\<FPG≤5.5mmol/L).
SitagliptinMetforminDose of 100 mg once a day administered with or without food.
Insulin GlargineMetforminAdministered once a day in the evening at dinner or at bedtime with a starting dose 0.2 U/kg. Then, the doses were to be individually adjusted, following a titration algorithm, to reach the FPG target: 70mg/dL\<FPG≤100mg/dL (3.9mmol/L\<FPG≤5.5mmol/L).
SitagliptinSitagliptinDose of 100 mg once a day administered with or without food.
Primary Outcome Measures
NameTimeMethod
HbA1c: Change From Baseline to Study Endpointbaseline (week 0), study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14

Change in HbA1c from baseline to study endpoint defined as the last available HbA1c value measured during the 24-week treatment period.

Secondary Outcome Measures
NameTimeMethod
HbA1c Response Rate: Percentage of Patients Who Reach the Target of HbA1c < 7% at Study Endpointstudy endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14
HbA1c Response Rate: Percentage of Patients Who Reach the Target of HbA1c < 6.5% at Study Endpointstudy endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14
Self-monitored Fasting Plasma Glucose (SMFPG) Mean : Change From Baseline to Study Endpointbaseline (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

SMFPG mean = mean of the fasting plasma glucose values recorded on the 6 consecutive days before the visit (at least 3 values needed).

Study endpoint was defined as the last available SMFPG mean value collected on-treatment.

Change= study endpoint - baseline

7-point Plasma Glucose Profile: Change From Baseline to Study Endpointbaseline (week 0), study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14

7-point plasma glucose recorded before and after breakfast, before and after lunch, before and after dinner and at bedtime.

Change = study endpoint - baseline.

Insulin Dose in the Insulin Glargine Groupvisit 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

Daily dose at the face-to-face visits.

Lipid Profile: Change From Baseline to Study Endpointbaseline (week 0), study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14
Change in Body Weight From Baseline to Study Endpointbaseline (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
Number of Patients With at Least One Episode of Symptomatic HypoglycemiaDuring the treatment phase (24 weeks) plus 7 days after last dose

Symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemia confirmed or not by a plasma glucose measurement \<= 70mg/dL \[3.9 mmol/L\]

Number of Patients With at Least One Episode of Severe Symptomatic HypoglycemiaDuring the treatment phase (24 weeks) plus 7 days after last dose

Severe symptomatic hypoglycemia was defined as an event with clinical symptoms which required assistance of another person and with either a Plasma Glucose level \< 36 mg/dL (2 mmol/L) or with a prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration

Trial Locations

Locations (1)

Sanofi-Aventis Administrative Office

🇬🇧

Guildford Surrey, United Kingdom

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