Metformin Glycinate on Metabolic Control and Inflammatory Mediators in Type 2 Diabetes

Type 2 Diabetes Clinical Trial

— COMET  

Official title:

Safety and Efficacy of Metformin Glycinate vs Metformin Hydrochloride on Metabolic Control and Inflammatory Mediators in Type 2 Diabetes Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01386671
• Other study ID #: GlyMet01_13062011
• Status: Completed
• Phase: Phase 3
• First received: June 29, 2011
• Last updated: January 26, 2018
• Start date: June 2014
• Est. completion date: January 2018

Study information

• Verified date: January 2018
• Source: Laboratorios Silanes S.A. de C.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 203
• Est. completion date: January 2018
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Metformin glycinate
Drug: Metformin glycinate 12 months: 1 month,one tablet 1050.6 mg once daily + 11 months, one tablet 1050.6 mg twice daily
• Metformin hydrochloride
12 months: 1 month, once daily dose of 850 mg (before dinner) and 11 months, twice daily dose 850 mg (before breakfast) + 850 mg (before dinner).

Locations

Country	Name	City	State
Mexico	Instituto de terapéutica experimental y clínica (INTEC)	Guadalajara	Jalisco
Mexico	Unidad Antidiabética Integral	Mexico City	AA
Mexico	Unidad de Investigacion en Epidemiologia Clinica. UMAE Hospital de Especialidades Centro Medico Nacional Siglo XXI. Instituto Mexicano del Seguro Social	Mexico City	Distrito Federal
Mexico	Paracelsus S.A. de C.V.	Mexico, city	AA

Sponsors (1)

Lead Sponsor	Collaborator
Laboratorios Silanes S.A. de C.V.

Country where clinical trial is conducted

Mexico, 

References & Publications (8)

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. — View 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. Erratum in: Lancet 1998 Nov 7;352(9139):1558. — View Citation

Hermann LS, Scherstén 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. — View 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. — View 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. — View 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. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glycosylated hemoglobin (HbA1c)	HbA1c: Measured by electrophoresis of lacked total blood using Paragon system and Appraise reader 44800 (Beckman Instruments de Mexico).; Fasting Glucose: in serum using glucose oxidase technique with BM/Hitachi 704/911 automated analyzer	12 months
Secondary	Fasting glucose		12 months
Secondary	Total cholesterol		12 months
Secondary	High-density lipoprotein (HDL)		12 months
Secondary	Low-density lipoprotein (LDL)		12 months
Secondary	Triglycerides		12 months
Secondary	Tumor necrosis factor-alpha (TNF-a)		12 months
Secondary	Adiponectin		12 months
Secondary	Resistin		12 months
Secondary	Interleukin-1 beta (IL-1ß)		12 months
Secondary	Number of Adverse Events as a Measure of Safety and Tolerability		12 months
Secondary	Malonylaldehyde		12 months
Secondary	Dismutase superoxide		12 months