Linagliptin in Combination With Metformin in Treatment Naive Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control

Phase 4

Completed

Conditions: Diabetes Mellitus, Type 2

Interventions: Drug: metformin placebo
Drug: metformin
Drug: linagliptin
Drug: linagliptin placebo

Registration Number: NCT01438814

Lead Sponsor: Boehringer Ingelheim

Brief Summary: The aim of this study is to investigate the impact of the combination therapy of linagliptin and metformin at submaximal doses in reduction of Glycosylated haemoglobin (HbA1c) and metformin pre-specified gastro-intestinal (GI) side effects in treatment naive patients of with type 2 diabetes mellitus.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 689

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
linagliptin + metformin	linagliptin	patients to receive linagliptin +metformin QD
metformin	metformin placebo	patients to receive metformin BID
metformin	linagliptin placebo	patients to receive metformin BID
linagliptin + metformin	metformin	patients to receive linagliptin +metformin QD
metformin	metformin	patients to receive metformin BID

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) After 14 Weeks Treatment	Baseline and 14 weeks	Adjusted mean change in HbA1c from baseline at Week 14 was analysed using an ANCOVA model. The Model included treatment and continuous baseline HbA1c.

Secondary Outcome Measures

Name	Time	Method
Occurence of Metformin Pre-specified Moderate to Severe GI Side Effects Assessed by Investigators During 14 Weeks of Treatment	14 weeks	Proportion of patients who experienced at least one metformin pre-specified moderate or severe GI side effect during 14 weeks
Composite Endpoint of Occurence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 14 Weeks of Treatment) and no Occurence of Moderate and Severe Metformin Pre-specified GI Side Effects Assessed by the Investigators During 14 Weeks	14 weeks	The proportion of patients who achieved all the targets in a composite endpoint (HbA1c lowered by at least 0.5% after 14 weeks of treatment; no occurrence of pre-specified moderate or severe GI side effects of metformin, as assessed by the investigators during 14 weeks of treatment).
Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 14 Weeks of Treatment)	14 weeks	The proportion of patients who achieved a relative efficacy response (HbA1c lowering by at least 0.5% after 14 weeks of treatment).
Metformin Pre-specified GI Symptom Intensity Score Assessed by Investigators During 14 Weeks of Treatment	14 weeks	Patients could experience multiple events, therefore, multiple answers were possible for each patient.
Composite Endpoint of Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <6.5% After 14 Weeks of Treatment, and no Occurrence of Moderate or Severe Metformin Pre-specified GI Side Effects Assessed by Investigators	14 weeks	The proportion of patients who achieved all the targets in a composite endpoint (HbA1c below 6.5% after 14 weeks of treatment; no occurrence of pre-specified moderate or severe GI side effects of metformin, as assessed by the investigators during 14 weeks of treatment).
Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.8% After 14 Weeks of Treatment)	14 weeks	The proportion of patients who achieved a relative efficacy response (HbA1c lowering by at least 0.8% after 14 weeks of treatment).
Change From Baseline in Body Weight by Visit at Week 14	Baseline and 14 weeks	Means are adjusted by treatment, continuous baseline HbA1c and continuous baseline weight
Change From Baseline in Fasting Plasma Glucose (FPG) After 14 Weeks of Treatment	Baseline and 14 weeks	Means are adjusted by treatment, continuous baseline HbA1c and continuous baseline fasting plasma glucose.
Change From Baseline in HbA1c Over Time	Baseline, 2 weeks and 8 weeks	Means are adjusted by treatment and continuous baseline HbA1c
Composite Endpoint of Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 14 Weeks of Treatment, on no Occurrence of Moderate or Severe Gastrointestinal (GI) Side Effects During 14 Weeks of Treatment	14 weeks	The proportion of patients who achieved all the targets in a composite endpoint (HbA1c below 7.0% after 14 weeks of treatment; no occurrence of pre-specified moderate or severe gastrointestinal (GI) side effects of metformin, as assessed by the investigators during 14 weeks of treatment)
Metformin Pre-specified GI Symptom Intensity Score Assessed by Patients During 14 Weeks of Treatment	14 weeks	The intensity of the GI side effects was also assessed by the patients using VAS scaled from 0 to 10; higher scores indicate more severe events. Means are adjusted by treatment and continuous baseline HbA1c.
Composite Endpoint of Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.8% After 14 Weeks of Treatment) and no Occurrence of Moderate and Severe Metformin Pre-specified GI Side Effects Assessed by Investigators During 14 Weeks	14 weeks	The proportion of patients who achieved all the targets in a composite endpoint (HbA1c lowered by at least 0.8% after 14 weeks of treatment; no occurrence of pre-specified moderate or severe GI side effects of metformin, as assessed by the investigators during 14 weeks of treatment).

Trial Locations

Locations (90): 1218.60.32001 Boehringer Ingelheim Investigational Site
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Genk, Belgium
1218.60.32005 Boehringer Ingelheim Investigational Site
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Ham, Belgium
1218.60.32004 Boehringer Ingelheim Investigational Site
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Natoye, Belgium
1218.60.50003 Boehringer Ingelheim Investigational Site
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Guatemala, Guatemala
1218.60.91005 Boehringer Ingelheim Investigational Site
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Coimbatore, India
1218.60.20004 Boehringer Ingelheim Investigational Site
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Halifax, Nova Scotia, Canada
1218.60.20014 Boehringer Ingelheim Investigational Site
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Coquitlam, British Columbia, Canada
1218.60.20001 Boehringer Ingelheim Investigational Site
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St-Romuald, Quebec, Canada
1218.60.20009 Boehringer Ingelheim Investigational Site
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Calgary, Alberta, Canada
1218.60.20010 Boehringer Ingelheim Investigational Site
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Surrey, British Columbia, Canada
1218.60.90001 Boehringer Ingelheim Investigational Site
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Dhaka, Bangladesh
1218.60.90002 Boehringer Ingelheim Investigational Site
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Dhaka, Bangladesh
1218.60.90003 Boehringer Ingelheim Investigational Site
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Dhaka, Bangladesh
1218.60.32002 Boehringer Ingelheim Investigational Site
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Hasselt, Belgium
1218.60.32003 Boehringer Ingelheim Investigational Site
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Tremelo, Belgium
1218.60.91010 Boehringer Ingelheim Investigational Site
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Bangalore, India
1218.60.52005 Boehringer Ingelheim Investigational Site
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Aguascalientes, Mexico
1218.60.52002 Boehringer Ingelheim Investigational Site
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Durango, Mexico
1218.60.52004 Boehringer Ingelheim Investigational Site
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Monterrey, Mexico
1218.60.51001 Boehringer Ingelheim Investigational Site
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Lima, Peru
1218.60.91008 Boehringer Ingelheim Investigational Site
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Kolkata, India
1218.60.91001 Boehringer Ingelheim Investigational Site
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Nagpur, India
1218.60.91007 Boehringer Ingelheim Investigational Site
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Nagpur, India
1218.60.91003 Boehringer Ingelheim Investigational Site
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Pune, India
1218.60.91006 Boehringer Ingelheim Investigational Site
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Pune, India
1218.60.96001 Boehringer Ingelheim Investigational Site
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Beirut, Lebanon
1218.60.96004 Boehringer Ingelheim Investigational Site
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Byblos, Lebanon
1218.60.96002 Boehringer Ingelheim Investigational Site
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Beirut, Lebanon
1218.60.96005 Boehringer Ingelheim Investigational Site
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Saida, Lebanon
1218.60.51004 Boehringer Ingelheim Investigational Site
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Piura, Peru
1218.60.96003 Boehringer Ingelheim Investigational Site
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Hazmieh, Lebanon
1218.60.52003 Boehringer Ingelheim Investigational Site
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Cuernavaca, Mexico
1218.60.52001 Boehringer Ingelheim Investigational Site
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Durango, Mexico
1218.60.51002 Boehringer Ingelheim Investigational Site
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Lima, Peru
1218.60.63001 Boehringer Ingelheim Investigational Site
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Cebu City, Philippines, Philippines
1218.60.63002 Boehringer Ingelheim Investigational Site
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Marikina City, Philippines, Philippines
1218.60.63004 Boehringer Ingelheim Investigational Site
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Iloilo City, Philippines, Philippines
1218.60.63003 Boehringer Ingelheim Investigational Site
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Manila, Philippines
1218.60.63005 Boehringer Ingelheim Investigational Site
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Quezon City, Philippines
1218.60.88006 Boehringer Ingelheim Investigational Site
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Chiayi County, Taiwan
1218.60.34005 Boehringer Ingelheim Investigational Site
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Centelles, Spain
1218.60.20003 Boehringer Ingelheim Investigational Site
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Burnaby, British Columbia, Canada
1218.60.20013 Boehringer Ingelheim Investigational Site
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London, Ontario, Canada
1218.60.20006 Boehringer Ingelheim Investigational Site
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London, Ontario, Canada
1218.60.86012 Boehringer Ingelheim Investigational Site
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Chengdu, China
1218.60.86009 Boehringer Ingelheim Investigational Site
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Shenyang, China
1218.60.86011 Boehringer Ingelheim Investigational Site
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Changsha, China
1218.60.86014 Boehringer Ingelheim Investigational Site
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Hubei, China
1218.60.86001 Boehringer Ingelheim Investigational Site
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Beijing, China
1218.60.49006 Boehringer Ingelheim Investigational Site
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Frankfurt, Germany
1218.60.86010 Boehringer Ingelheim Investigational Site
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Chongqing, China
1218.60.86007 Boehringer Ingelheim Investigational Site
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Nanjing, China
1218.60.20015 Boehringer Ingelheim Investigational Site
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Hamilton, Ontario, Canada
1218.60.49001 Boehringer Ingelheim Investigational Site
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Unterschneidheim, Germany
1218.60.49002 Boehringer Ingelheim Investigational Site
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Neuwied, Germany
1218.60.49005 Boehringer Ingelheim Investigational Site
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Dresden, Germany
1218.60.34002 Boehringer Ingelheim Investigational Site
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Barcelona, Spain
1218.60.86013 Boehringer Ingelheim Investigational Site
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Hubei, China
1218.60.86005 Boehringer Ingelheim Investigational Site
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Shanghai, China
1218.60.86003 Boehringer Ingelheim Investigational Site
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Beijing, China
1218.60.49004 Boehringer Ingelheim Investigational Site
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Erfurt, Germany
1218.60.34009 Boehringer Ingelheim Investigational Site
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Granada, Spain
1218.60.86008 Boehringer Ingelheim Investigational Site
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Wuxi, China
1218.60.88001 Boehringer Ingelheim Investigational Site
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Taichung, Taiwan
1218.60.49007 Boehringer Ingelheim Investigational Site
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Berlin, Germany
1218.60.49003 Boehringer Ingelheim Investigational Site
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Hamburg, Germany
1218.60.50001 Boehringer Ingelheim Investigational Site
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Guatemala, Guatemala
1218.60.50002 Boehringer Ingelheim Investigational Site
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Guatemala, Guatemala
1218.60.88002 Boehringer Ingelheim Investigational Site
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Tainan,, Taiwan
1218.60.88004 Boehringer Ingelheim Investigational Site
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Taipei County, Taiwan
1218.60.34004 Boehringer Ingelheim Investigational Site
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Barcelona, Spain
1218.60.34007 Boehringer Ingelheim Investigational Site
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Mataró, Spain
1218.60.34010 Boehringer Ingelheim Investigational Site
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Valencia, Spain
1218.60.88003 Boehringer Ingelheim Investigational Site
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Kaohsiung,, Taiwan
1218.60.34008 Boehringer Ingelheim Investigational Site
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L'Hospitalet de Llobregat, Spain
1218.60.88007 Boehringer Ingelheim Investigational Site
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Taichung, Taiwan
1218.60.20012 Boehringer Ingelheim Investigational Site
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Corunna, Ontario, Canada
1218.60.20011 Boehringer Ingelheim Investigational Site
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Sarnia, Ontario, Canada
1218.60.20007 Boehringer Ingelheim Investigational Site
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Toronto, Ontario, Canada
1218.60.20005 Boehringer Ingelheim Investigational Site
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Strathroy, Ontario, Canada
1218.60.20002 Boehringer Ingelheim Investigational Site
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Sarnia, Ontario, Canada
1218.60.20016 Boehringer Ingelheim Investigational Site
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Toronto, Ontario, Canada
1218.60.49008 Boehringer Ingelheim Investigational Site
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Berlin, Germany
1218.60.91004 Boehringer Ingelheim Investigational Site
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Aurangabad, India
1218.60.34006 Boehringer Ingelheim Investigational Site
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Borges del Camp- Tarragona, Spain
1218.60.34001 Boehringer Ingelheim Investigational Site
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Barcelona, Spain
1218.60.34003 Boehringer Ingelheim Investigational Site
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Barcelona, Spain
1218.60.86006 Boehringer Ingelheim Investigational Site
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Nanjing, China
1218.60.85002 Boehringer Ingelheim Investigational Site
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Hong Kong, Hong Kong
1218.60.85001 Boehringer Ingelheim Investigational Site
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Hong Kong, Hong Kong