Clinical trial NCT01386671: Metformin Glycinate on Metabolic Control and Inflammatory Mediators in Type 2 Diabetes
Official title: Safety and Efficacy of Metformin Glycinate vs Metformin Hydrochloride on Metabolic Control and Inflammatory Mediators in Type 2 Diabetes Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes
Keywords: Type 2 Diabetes
metformin glycinate
metabolic control
Lead sponsor: Laboratorios Silanes S.A. de C.V.
Sponsor class: INDUSTRY
First posted: 2011-07-01
Enrollment: 203
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to compare the efficacy and safety of Metformin Glycinate versus Metformin Hydrochloride in metabolic control and inflammatory mediators in Mexican type 2 diabetes patients, in a 12 months follow up.

Detailed description: Metformin glycinate salt is a new drug , which has better pharmacokinetic characteristics (better bioavailability and absorption) making a proper antihyperglycemic power without increasing the frequency of adverse effects. The drug has been tested in preclinical test with animals, in healthy subjects and in patients with type 2 diabetes; which showed that it has adequate antihyperglycemic effect. Now, its important to compare metformin glycinate and metformin hydrochloride for evaluate the relative antihyperglicemic power. In addition, a study with a larger number of patients improve the statistical power of the test to investigate the effects of these drugs on possible weight loss and lipid profile improve. Additionally, it will also explore the relative power of the two medications tested to modify inflammatory response mediators and oxidative stress have been associated with the incidence of cardiovascular disease in diabetes. This project was designed with the intent to answer the next question: What are the efficacy and safety of metformin glycinate dose of 2101.2 mg/day (equivalent to 1700 mg/day metformin hydrochloride), compared with metformin hydrochloride in doses of 1700 mg/day for 12 months of treatment in patients with Type 2 diabetes.

Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes according ADA
* Less than a year of evolution since diagnosis
* Without antihyperglycemic pharmacological treatment
* HbA1c between 6.5% and 9.5%
* Stable weight during the last 6 months
* Body Mass Index ≥ 25 kg/m2 and \<35kg/m2.
* Blood pressure ≤ 130/80 mmHg
* Childbearing women under contraceptive treatment
* Signed Informed Consent Form
* Age from 18 to 70 years old

Exclusion Criteria:

* Non-fulfilment treatment in the screening period
* Smoking up to 1 year before the initial examination
* Drugs or alcohol abuse
* Creatinine depuration estimated with MDRD formula using serum creatinine \< 90 ml/min/1.72m2
* History of chronic liver disease, ALT or AST ≥ 2 times from the normal superior limit, or GGT ≥ 3 times from the normal superior limit.
* Chronic lung disease, that causes dyspnea equivalent to a functional class ≥3 (NYHA)or that requires oxygen supplementation.
* History or symptoms of coronary artery disease (CAD) or cerebrovascular disease (CVD).
* Drug treatment that interact with biguanides.
* Another chronic diseases that restricts survival or associated with chronic inflammation like: cancer, leukemia, lymphoma, erythematosus lupus, asthma, rheumatoid arthritis or infection for HIV.
* Pregnancy or positive pregnancy test in women under 50 years old or breastfeeding.

Primary outcomes:
measure: Glycosylated hemoglobin (HbA1c)
timeFrame: 12 months
Secondary outcomes:
measure: Fasting glucose
timeFrame: 12 months
measure: Total cholesterol
timeFrame: 12 months
measure: High-density lipoprotein (HDL)
timeFrame: 12 months
measure: Low-density lipoprotein (LDL)
timeFrame: 12 months
measure: Triglycerides
timeFrame: 12 months
measure: Tumor necrosis factor-alpha (TNF-α)
timeFrame: 12 months
measure: Adiponectin
timeFrame: 12 months
measure: Resistin
timeFrame: 12 months
measure: Interleukin-1 beta (IL-1β)
timeFrame: 12 months
measure: Number of Adverse Events as a Measure of Safety and Tolerability
timeFrame: 12 months
measure: Malonylaldehyde
timeFrame: 12 months
measure: Dismutase superoxide
timeFrame: 12 months
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Unidad Antidiabética Integral
state: AA
city: Mexico, city
country: Mexico
facility: Paracelsus S.A. de C.V.
state: AA
city: Mexico City
country: Mexico
facility: Unidad de Investigacion en Epidemiologia Clinica. UMAE Hospital de Especialidades Centro Medico Nacional Siglo XXI. Instituto Mexicano del Seguro Social
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Instituto de terapéutica experimental y clínica (INTEC)
state: Jalisco
Study officials:
affiliation: IMSS
name: Niels H Wacher, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hermann LS, Schersten B, Melander A. Antihyperglycaemic efficacy, response prediction and dose-response relations of treatment with metformin and sulphonylurea, alone and in primary combination. Diabet Med. 1994 Dec;11(10):953-60. doi: 10.1111/j.1464-5491.1994.tb00253.x.
citation: Johnson JA, Simpson SH, Toth EL, Majumdar SR. Reduced cardiovascular morbidity and mortality associated with metformin use in subjects with Type 2 diabetes. Diabet Med. 2005 Apr;22(4):497-502. doi: 10.1111/j.1464-5491.2005.01448.x.
citation: Phung OJ, Scholle JM, Talwar M, Coleman CI. Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. JAMA. 2010 Apr 14;303(14):1410-8. doi: 10.1001/jama.2010.405.
citation: Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):854-65.
citation: Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008 Oct 9;359(15):1577-89. doi: 10.1056/NEJMoa0806470. Epub 2008 Sep 10.
citation: Tzoulaki I, Molokhia M, Curcin V, Little MP, Millett CJ, Ng A, Hughes RI, Khunti K, Wilkins MR, Majeed A, Elliott P. Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. BMJ. 2009 Dec 3;339:b4731. doi: 10.1136/bmj.b4731.
citation: Selvin E, Bolen S, Yeh HC, Wiley C, Wilson LM, Marinopoulos SS, Feldman L, Vassy J, Wilson R, Bass EB, Brancati FL. Cardiovascular outcomes in trials of oral diabetes medications: a systematic review. Arch Intern Med. 2008 Oct 27;168(19):2070-80. doi: 10.1001/archinte.168.19.2070.
citation: Alexander GC, Sehgal NL, Moloney RM, Stafford RS. National trends in treatment of type 2 diabetes mellitus, 1994-2007. Arch Intern Med. 2008 Oct 27;168(19):2088-94. doi: 10.1001/archinte.168.19.2088.