Metformin is the frontline agent for diabetes treatment;Its hypoglycemic effect is attributed to the decrease in the liver production of glucose and increased insulin sensitivity in muscle tissue.In addition, metformin delays intestinal glucose absorption.The immediate release metformin preparation (M-LI) is administered 3 times per day, in doses of 500, 850 and 1000 mg per tablet.
Recently, a prolonged liberation metformin preparation (M-LP) was introduced that can be administered once a day and has the same effectiveness, but better tolerability compared to the M-LI.To date, there are no clinical comparison studies between the M-LI and the M-LP;The objective of this work was to compare the effects of both prepared in terms of gastrointestinal tolerability and blood glucose control.
patients and methods
The study, randomized and controlled, was carried out at the Center of Diabetes and Metabolic Deseosses, IRCCS Polyclinic San Matteo, Pavia, Italy;The recruitment took place between 2014 and 2016.
253 Caucasian patients of 18 years or more with type 2 diabetes were evaluated, without adequate metabolic control despite the diet (levels of glucosylated hemoglobin [HBA1C] & GT; 7% Y & LT; 8.5%), according to the criteria of the European Societyof Cardiology and the European Association for the Study of Diabetes.
Patients were randomly assigned to M-Li or M-LP treatment for 6 months, in the maximum tolerated dose, depending on gastrointestinal adverse effects.The average dose administered in the patients assigned to M-LI and M-LP was 2000 ± 1000 mg/d and 1000 ± 500 mg/d, respectively.The subjects had to perform strict nutritional control, with an approximate caloric deficit of 600 kcal per day, according to the recommendations of the American Heart Association.
All participants were performed interrogation, complete physical examination and electrocardiogram of 12 derivations.At the beginning and at 3 and 6 months of therapy, body weight, HBA1C levels, fasting and postprandial glycemia, fasting insulinemia and insulin resistance were determined, according to the homeostasis model (homa-ir).
Lipid levels, tumor necrosis factor Alfa (TNF-A, for its acronym in English), ultrasensitive, visface and vasipine protein (PCR) factor were also analyzed.At the beginning and at 6 months, patients completed the SF-36 Health Survey, Diabetes Quality of Life modified Questionnaire (DQOL/MOD) and the Treatment Diabetes satisfaction Questionnaire (DTSQ), in its validated Italian versions.
Results
A total of 125 and 128 patients were assigned to M-LI treatment with M-LP, respectively;235 of the 253 patients completed the study.
At 6 months of therapy, a similar reduction in body weight, body mass index (BMI) and abdominal circumference in both groups (P&T 0.05) were proven, without important differences between them.The circumference of the waist and the hip were not modified in any of the groups.
At 3 months of treatment, the 2 preparations were associated with similar control of HBA1C levels and postprandial blood glucose (P&R 0.05 with respect to basal values), without important differences between groups.However, only M-LP therapy decreased fasting glycemia compared to basal values (P&T 0.05).
On the other hand, at 6 months of therapy, the M-LP was associated with the most important reductions in HBA1C, postprandial blood glucose and fasting blood glucose with respect to basal values (P&T 0.01) and compared to the administration ofM-LI (P&T 0.05).
At 6 months, a significant reduction of ease and homa-ri insulinemia was proven inthe 2 groups;However, the M-LP exerted more important effects on the homa-ri regarding basal values (P&T 0.01) and M-Li treatment (P&T 0.05).
Compared to the use of M-LI, the treatment with M-LP induced decreases in serum levels of total cholesterol and cholesterol associated with low density lipoproteins (LDLC; P&T 0.05 with respect to the starting values and those recordedin the group with M-Li).
Likewise, M-LP treatment was associated with reducing triglycerides (P&R 0.05 compared to basal values, but not those observed in the M-Li group).No changes in cholesterol levels associated with high density lipoproteins.
M-LP treatment was related to significant reductions in serum levels of TNF-A, PCR and Vaspan;These effects were not observed in patients who used M-LI.The M-LP also induced increases in the visimum concentration (P&R 0.05 with respect to the starting values).The serum TNF-A and PCR levels were lower, while the visimum concentration was higher, in the M-LP-treated group compared to the group with M-Li (P& LT; 0.05 in all cases all cases) at 6 months of treatment.
The adverse effects were more frequent with the M-LI at 3 months (P&R 0.05 compared to M-LP therapy) and at 6 months (P&R 0.01 with respect to treatment with M-LP).
In the SF-36 Health Survey an increase in the score of the 2 questions linked to the perception of general health was proven;The score was higher in the group that received M-LP compared to the subjects assigned to M-Li.
In the DQOL/MOD, the treatment with M-LP for 6 months was associated with lower scores, that is, with less adverse influence of diabetes and treatment on the quality of life.The level of satisfaction, judging by the results of the DTSQ, was more favorable with the M-LP compared to the M-LI.No differences were observed in the questions that reflect the perceptions related to hypoglycemia and hyperglycemia.
discussion
The present study showed greater efficacy for the M-LP, with respect to the M-LI, in the control of blood glucose and metabolic control.M-LP treatment was associated with improvements in total cholesterol and LDLC levels, compared to the use of M-LI;The favorable effects of metformin on the lipid profile were observed in animal studies and were confirmed in humans.
The M-LP improved visimum levels, an effect that was not achieved with the M-LI.Visphatine is a protein synthesized by adipheose, muscle and bone marrow cells, and lymphocytes.It exerts effects similar to those of insulin on fat and liver cells in culture, and reduces plasma glucose concentration in mice.
It binds to insulin receptors with the same affinity, but in a different site, and induces awareness of the hormone.Probably the lower glycemia control with M-LI is due to the intermittent control of glucose in plasma.M-LP therapy has better adhesion, an effect that would also explain its advantages in relation to the M-LI.In a study, compliance with the treatment was linked to its complexity, the total dose number per day, the size of the tablets, the difficulties in swallowing, the adverse effects and the costs.
The levels of inflammatory markers TNF-A and PCR were lower in the patients assigned to M-LP treatment with respect to the initial values and those recorded in the M-LI group.It is known that hyperglycemia is accompanied by endothelial damage and that postprandial hyperglycemia induces acute systemic inflammation repeated inpatients with disorders in glucose metabolism.M-LP is related to better glycemia control, less endothelial damage and reduction of inflammatory markers.
The use of different doses of M-Li and M-LP was a limitation of this study;However, when considering the entire cohort, the 2 preparations were used in an average dose ± 50% of the dose.
Conclusion
The findings of this study suggest that M-LP treatment is associated with better glycemia and metabolic control, better lipid profile and improvement in some cytokines compared to M-LI therapy.
SIIC- Ibero-American Society of Scientific Information.