Clinical trial NCT02064881: Efficacy Study of Metformin Glycinate on Postprandial Lipemia
Official title: Effect of Metformin Glycinate on Postprandial Lipemia, Glycemic Control and Oxidation Markers in Type 2 Diabetes Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Type 2 Diabetes
Keywords: Postprandial lipemia
Diabetes
Metformin glycinate
oxidized LDL
Lead sponsor: Laboratorios Silanes S.A. de C.V.
Sponsor class: INDUSTRY
Collaborators: name: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
First posted: 2014-02-17
Enrollment: 72
Sex: ALL
Minimum age (years): 35
Maximum age (years): 65
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 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in postprandial lipemia at 4 months
timeFrame: baseline, 4 months
Secondary outcomes:
measure: Change in oxidized LDL at 4 months
timeFrame: baseline, 4 months
measure: Change in FGF-21 levels at 4 months
timeFrame: baseline, 4 months
measure: Change in A1C at 4 months
timeFrame: baseline, 4 months
measure: Change in alanine aminotransferase at 4 months
timeFrame: baseline, 4 months
measure: Change in uric acid at 4 months
timeFrame: baseline, 4 months
measure: Number of Participants with Serious and Non-Serious Adverse Events
timeFrame: up to 4 months
Other outcomes:
Locations:
city: México
country: Mexico
facility: Instituto Nacional de Ciencias Médicas Y Nutrición Salvador Zubirán
state: Distrito Federal
Study officials:
affiliation: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
name: Francisco J Gómez, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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: 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.
citation: 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.
citation: 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.