Health Condition 1: null- Patients with type 2 diabetes mellitus at high cardiovascular risk
Conditions
Interventions
Intervention1: Linagliptin (BI Linagliptin): Pharmaceutical form: tablet
Source: Boehringer Ingelheim Pharma GmbH & Co. KG
Unit Strength: 5 mg
Route of administration: p.o., once daily
Treatment durat
Sponsors
Boehringer Ingelheim Pharmaceuticals
Eli Lilly and Company
Eligibility
Inclusion criteria
Inclusion criteria: Documented diagnosis of T2DM and concurrently 1) insufficient glycaemic control and 2) a high risk of CV events prior to informed consent 1) Insufficient glycaemic control (at Visit 1a) defined as: a) HbA1c 6.5 - 8.5% (48 - 69 mmol/mol) while patient is treatment naïve or treated with: - metformin monotherapy, or - alpha-glucosidase inhibitor monotherapy (e.g. acarbose, voglibose), or - metformin + alpha-glucosidase inhibitor (e.g. acarbose, voglibose), or b) HbA1c 6.5 - 7.5% (48 - 58 mmol/mol) while patient is treated with - sulphonylurea (SU) monotherapy, or - glinide monotherapy (e.g. repaglinide, nateglinide), or - metformin + sulphonylurea (combination maximal up to 5 years), or - metformin + glinide (combination maximal up to 5 years) 2) High risk of CV events defined as any one (or more) of A), B), C) or D): A) Previous Vascular Disease: - Myocardial infarction ( > 6 weeks prior to informed consent) - Documented coronary artery disease (≥50% luminal diameter narrowing of left main coronary artery or in at least two major coronary arteries in angiogram) - Percutaneous Coronary Intervention (PCI) > 6 weeks prior informed consent - Coronary Artery By-pass Grafting (CABG) > 4 years prior to informed consent or with recurrent angina following surgery - Ischemic or hemorrhagic stroke ( > 3 months prior to informed consent) - Peripheral occlusive arterial disease (previous limb bypass surgery or percutaneous transluminal angioplasty; previous limb or foot amputation due to circulatory insufficiency, angiographic or ultrasound detected significant vessel stenosis ( >50%) of major limb arteries (common iliac artery, internal iliac artery, external iliac artery, femoral artery, popliteal artery), history of intermittent claudication, with an ankle: arm blood pressure ratio B) Evidence of vascular related end-organ damage: - Moderately impaired renal function (as defined by modified diet of renal disease (MDRD) formula) with estimated glomerular filtration rate [eGFRF]) 30-59 mL/min/1.73 m2 - Random spot urinary albumin:creatinine ratio ≥ 30 μg/mg in two of three unrelated specimens in previous 12 months prior Visit 1a - Proliferative retinopathy defined as retinal neovascularisation or previous retinal laser coagulation therapy. D) At least two of the following CV risk factors: - Type 2 diabetes mellitus duration > 10 years at Visit 1a. - Systolic blood pressure (SBP) > 140 mmHg (or on at least one blood pressure lowering treatment at Visit 1a) - Current daily cigarette smoking - LDL cholesterol ≥ 135 mg/dL (3.5 mmol/l) (or specific current treatment for this lipid abnormality) at Visit 1a 3) Body Mass Index (BMI) ≤ 45 kg/m2 at Visit 1a 4) Age ≥ 40 and ≤ 65 years at Visit 1a 5) Signed and dated written informed consent at the latest by the date of Visit 1a, in accordance with GCP and local legislation
Exclusion criteria
Exclusion criteria: 1) Type 1 diabetes mellitus 2) Treatment with other antidiabetic drugs (e.g. rosiglitazone, pioglitazone, GLP-1 analogue/agonists, DPP-IV inhibitors or any insulin) prior to informed consent. Note: previous short term use of insulin (up to two weeks) is allowed (e.g. during hospitalisation) if taken at least 8 weeks prior informed consent. 3) Treatment with anti-obesity drugs (e.g. sibutramine, orlistat) 3 months prior to informed consent 4) Uncontrolled hyperglycaemia with a glucose level greater than 240 mg/dl (greater than 13.3 mmol/L) after an overnight fast during placebo run-in and confirmed by a second measurement(not on the same day). 5) Active liver disease or impaired hepatic function, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined at Visit 1a. 6) Any previous (or planned within next 12 months) bariatric surgery (open or laparascopic) or intervention (gastric sleeve) 7) Pre-planned coronary artery re-vascularization (PCI, CABG) within next 6 months 8) Known hypersensitivity or allergy to the investigational product or its excipients, metformin or glimepiride 9) Inappropriateness of glimepiride treatment for renal safety issues according to local prescribing information 10) Congestive heart failure of NYHA class III or IV 11) Acute or chronic metabolic acidosis (present condition in patient history) 12) Hereditary galactose intolerance 13) Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation 14) Current treatment with systemic steroids at time of informed consent or pre-planned initiation of such therapy. Note: inhaled use of steroids (e.g. for asthma/COPD) is no exclusion criterion, as this does not cause systemic steroid action. 15) Change in dose of thyroid hormones within 6 weeks prior informed consent 16) Participation in another trial with an investigational drug given within 2 months prior to informed consent 17) Pre-menopausal women (last menstruation less than or equal to 1 year prior to informed consent) who: - are nursing or pregnant, - or are of child-bearing potential and are not practicing an acceptable method of birth control (acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives and vasectomised partner) or do not plan to continue using acceptable method of birth control throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial. 18) Patients considered unreliable by the investigator concerning the requirements for follow-up during the study and/or compliance with study drug administration, has a life expectancy less than 5 years for non-CV causes, or has cancer other than nonmelanoma skin cancer within last 3 years, or has any other condition than mentioned which in the opinion of the investigator, would not allow safe participation in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - cardiovascular death - non fatal myocardial infarction - non fatal stroke (ischemic/hemorrhagic/etiology unknown) - hospitalisation for unstable anginaTimepoint: From patients randomization until final visit (end of study visit) + 30 days. | — |
Secondary
| Measure | Time frame |
|---|---|
| composite endpoint of (treatment sustainability defined as the proportion of patients that are on study treatment at study end, that at Final Visit maintain glycaemic control (HbA1c less than or equal to 7.0%) without need for rescue medication (between end of titration [Visit 6] and Final Visit) and patients without any moderate/severe hypoglycaemic episodes (between Visit 6 and Final Visit) and without greater than 2% weight gain at Final Visit (between Visit 6 and Final Visit))Timepoint: Between visit 6 and final visit.;composite endpoint of (treatment sustainability defined as the proportion of patients that are on study treatment at study end, that at Final Visit maintain glycaemic control (HbA1c les than or equal to 7.0%) without need for rescue medication (between Visit 6 and Final Visit) and patients without greater than 2% weight gain at Final Visit (between Visit 6 and Final Visit))Timepoint: Between visit 6 and final visit.;Composite endpoint of all CEC confirmed adjudicated events (see tertiary cardiovascular endpoints)Timepoint: -;MACE composite endpoint: CV death (including fatal stroke and fatal MI), nonfatal MI and non-fatal strokeTimepoint: - | — |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czech Republic, Finland, France, Georgia, Germany, Greece, Hungary, India, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, New Zealand, Norway, Peru, Philippines, Portugal, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Tunisia, Ukraine, United Kingdom, United States of America
Contacts
Public ContactDr Partha Gokhale
Boehringer Ingelheim India Pvt. Ltd.
Outcome results
None listed