Efficacy Study of Metformin Glycinate on Postprandial Lipemia

Effect of Metformin Glycinate on Postprandial Lipemia, Glycemic Control and Oxidation Markers in Type 2 Diabetes Patients

The aim of this study is to evaluate the effect of metformin glycinate vs metformin hydrochloride on postprandial lipemia. 72 patients will be included, they will be randomized and assigned into one of the two treatment groups: metformin glycinate 1240 mg BID or metformin hydrochloride 1000 mg BID (36 patients per group). The patients will be followed for 4 months.

Blood count, blood chemistry, liver profile, lipid profile, HbA1c, apolipoprotein B, oxidized LDL, fibroblast growth factor 21, leptin, adiponectin, C-reactive protein, free fatty acids, fibrinogen, Goodpasture Binding Protein (GPBP) and antioxidant activity of plasma will be measured at baseline and 4 months.

Additionally, after a structured meal, the following parameters will be measured: glucose, insulin, triglycerides, apolipoprotein B and oxidized LDL. (baseline and 4 months). Throughout the study adverse events will be documented.

Study Overview

• Status: Unknown
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Metformin glycinate; Drug: Metformin Hydrochloride

Detailed Description

Main objective: To compare the effect of metformin glycinate with metformin hydrochloride postprandial lipemia (area under the curve of triglycerides)

Study group

Tablets of 620 mg of metformin glycinate. Scaling: 1 tablet at night for 3 days, followed by 1 tablet in the morning and 1 tablet at night for 3 days, followed by 1 tablet in the morning and 2 tablets in the evening for 3 days and finally, 2 tablets in the morning and 2 tablets in the evening to complete the study. Final study dose 1240 mg every 12 hours.

Comparative group

500 mg tablets of metformin hydrochloride. Scaling: 1 tablet at night for 3 days, followed by 1 tablet in the morning and 1 tablet at night for 3 days, followed by 1 tablet in the morning and 2 tablets in the evening for 3 days and finally, 2 tablets in the morning and 2 tablets in the evening to complete the study. Final study dose 1000 mg every 12 hours.

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Mexico
  • Distrito Federal
    • México, Distrito Federal, Mexico, 14000
      • Recruiting
      • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
      • Contact: Francisco Gómez, Doctor; Phone Number: 55133891; Email: gomezperezfco@gmail.com
      • Contact: Paloma Almeda, Doctor; Phone Number: 56554523; Email: palomaalmeda@yahoo.com
      • Principal Investigator: Francisco J Gómez, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients of both sexes
• Between 35 and 65 years old
• Patients with type 2 diabetes within two years of diagnosis according to the ADA criteria
• Overweight patients (BMI between 25.5 and 29.9 kg/m2) or with grade 1 obesity (BMI between 30.0 and 34.9 kg/m2), according to WHO classification
• Low HDL levels: <50 in women and <40 mg/dL in men
• Hypertriglyceridemia: >150 and less than 300 mg/dL
• Patients who had not taken antidiabetes drug treatment or with diet and exercise treatment, or with metformin or DPP4 inhibitor monotherapy
• HbA1c between 6.5 and 8.5%.
• Creatinine clearance >60 ml/min (calculated by Cockcroft and Gault)
• Informed consent form signed.
• Women using contraception.

Exclusion Criteria:

• Patients with other types of diabetes (type 1, LADA, MODY, etc.).
• Patients with primary dyslipidemia.
• Patients with poorly substituted hypothyroidism TSH > 5 mU/mL.
• Patients hospitalized in the last month.
• Patients with a disease of poor short-term prognosis
• Patients with autoimmune or rheumatic diseases.
• Patients with acute infection or febrile illness.
• History of chronic liver disease or ALT or AST ≥ 2.0 times the upper limit of normal, or GGT ≥ 3 times the upper limit of normal.
• Patients with any other chronic disease, for example: HIV, rheumatic diseases.
• Pregnant or positive pregnancy test.
• Women who are breastfeeding.
• Patients in another research project.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: metformin glycinate; 620mg tablets of metformin glycinate: 1 tablet by mouth at night for 3 days, 1 tablet in the morning and evening for 3 days, 1 tablet in the morning and 2 tablets in the evening for 3 days and 2 tablets in the evening and 2 tablets in the morning until the end of the study. Total study dose: 1240mg every 12 hours.	Drug: Metformin glycinate; All patients are going to begin the treatment with one tablet orally at night, 30 minutes before dinner (1 tablet of 620 mg glycinate metformin or one 500 mg tablet of metformin hydrochloride) and the dose will be administrated every 3 days to complete the dose of 2 tablets in the morning 30 minutes before breakfast and 2 tablets in the evening 30 minutes before dinner (1240 mg metformin glycinate every 12 hours or 1000 mg metformin hydrochloride every 12 hrs) .; Other Names: DMMET-01
Active Comparator: metformin hydrochloride; 500mg tablets of metformin hydrochloride:1 tablet by mouth at night for 3 days, 1 tablet in the morning and evening for 3 days, 1 tablet in the morning and 2 tablets in the evening for 3 days and 2 tablets in the evening and 2 tablets in the morning until the end of the study. Total study dose: 1000mg every 12 hours.	Drug: Metformin Hydrochloride; All patients are going to begin the treatment with one tablet orally at night, 30 minutes before dinner (1 tablet of 620 mg glycinate metformin or one 500 mg tablet of metformin hydrochloride) and the dose will be administrated every 3 days to complete the dose of 2 tablets in the morning 30 minutes before breakfast and 2 tablets in the evening 30 minutes before dinner (1240 mg metformin glycinate every 12 hours or 1000 mg metformin hydrochloride every 12 hrs); Other Names: HCL MET

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in postprandial lipemia at 4 months	baseline, 4 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Serious and Non-Serious Adverse Events	up to 4 months
Change in oxidized LDL at 4 months	baseline, 4 months
Change in FGF-21 levels at 4 months	baseline, 4 months
Change in A1C at 4 months	baseline, 4 months
Change in alanine aminotransferase at 4 months	baseline, 4 months
Change in uric acid at 4 months	baseline, 4 months

Collaborators and Investigators

• Sponsor: Laboratorios Silanes S.A. de C.V.
• Collaborators: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Investigators: Principal Investigator: Francisco J Gómez, Doctor, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Publications and helpful links

General Publications

• 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.
• Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR; American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD). Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012 Jun;35(6):1364-79. doi: 10.2337/dc12-0413. Epub 2012 Apr 19. No abstract available. Erratum In: Diabetes Care. 2013 Feb;36(2):490.
• Schramm TK, Gislason GH, Vaag A, Rasmussen JN, Folke F, Hansen ML, Fosbol EL, Kober L, Norgaard ML, Madsen M, Hansen PR, Torp-Pedersen C. Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study. Eur Heart J. 2011 Aug;32(15):1900-8. doi: 10.1093/eurheartj/ehr077. Epub 2011 Apr 6. Erratum In: Eur Heart J. 2012 May;33(10):1183.
• Masoudi FA, Inzucchi SE, Wang Y, Havranek EP, Foody JM, Krumholz HM. Thiazolidinediones, metformin, and outcomes in older patients with diabetes and heart failure: an observational study. Circulation. 2005 Feb 8;111(5):583-90. doi: 10.1161/01.CIR.0000154542.13412.B1.
• Roussel R, Travert F, Pasquet B, Wilson PW, Smith SC Jr, Goto S, Ravaud P, Marre M, Porath A, Bhatt DL, Steg PG; Reduction of Atherothrombosis for Continued Health (REACH) Registry Investigators. Metformin use and mortality among patients with diabetes and atherothrombosis. Arch Intern Med. 2010 Nov 22;170(21):1892-9. doi: 10.1001/archinternmed.2010.409.

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Anticipated): April 1, 2020
• Study Completion (Anticipated): August 1, 2020

Study Registration Dates

• First Submitted: February 14, 2014
• First Submitted That Met QC Criteria: February 14, 2014
• First Posted (Estimate): February 17, 2014

Study Record Updates

• Last Update Posted (Actual): January 30, 2018
• Last Update Submitted That Met QC Criteria: January 26, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Diabetes; Postprandial lipemia; oxidized LDL; Metformin glycinate
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Lipid Metabolism Disorders; Dyslipidemias; Diabetes Mellitus, Type 2; Hyperlipidemias; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: DMMET_LP001