Preliminary Comparison And Safety Analysis Of Modified-release Gliclazide Combined With Morning Or Evening Taking Metformin In Patients With Newly Diagnosed Type2Diabetes Mellitus

Background and ObjectiveType2diabetes mellitus (T2DM) is currently considered to be a complex, polygenetic hereditary disease caused by the combination of environmental factors and genetic predisposition and characterized by insulin resistance, relative insulin deficiency and increased output of liver glycogen. According to the statistics of the International Diabetes Federation (IDF), there were about100million diabetic patients, the figure mushroomed and quickly reached246million in2007. It was estimated that there would be380million patients suffer from diabetes mellitus around the world till2025. From2007to2008, an epidemiological survey conducted by Chinese Diabetes Society (CDS) covered14provinces and cities preliminarily estimated that the prevalence of diabetes was9.7%in adult Chinese above20years old after weighted analysis and considering all the influential factors such as gender, age, regional difference, urban and rural distribution. There are about92.4million adult diabetic patients in China, including43.1million in rural areas and around49.3million in cities. A survey carried out by Ministry of Health showed there are approximately3000newly diagnosed diabetic patients with an increase of1.2million each year within which95%are type2diabetes mellitus. China may have the largest number of people with diabetes mellitus in the world.Metformin is now used as the first-line drug in the treatment of T2DM, especially applied to those who are obese. In1998, the United Kingdom Prospective Diabetes Study (UKPKD) reported that metformin could restrain the formation of atherosclerosis, then found that metformin could improve insulin resistance (metabolic syndrome); another landmark study, American Diabetes Prevention Study (DPP) reported the potential preventive effects of metformin. Researches of clinical drugs always reveal tiny surprises. Clinical and experimental studies in recent years show that metformin could improve the glucose level, lipid spectrum, body weight and body fat distribution, but none of them expound that taking metformin on different time whether or not will have different treatment effects. This study aims at probing into preliminary comparison and safety analysis of modified-release gliclazide combined with morning or evening taking metformin in patients with newly diagnosed type2diabetes mellitus.Materials and Methods60outpatients were randomly assigned into two groups according to their clinic sequence, odd numbers grouped A while even numbers grouped B. Based on diet controlling and exercise therapy, patients in group A received gliclazide modified-release tablet (Diamicron, produced by Servier. corp. Tianjin)60mg (2tablets) once daily before breakfast and metformin (Glucophage, produced by Bristol Myers Squibb, corp., Shanghai)850mg (1tablet) once daily after breakfast; patients in group B received gliclazide modified-release tablet (Diamicron, produced by Servier. corp. Tianjin)60mg (2tablets) once daily before breakfast and metformin (Glucophage produced by Bristol Myers Squibb. corp., Shanghai)850mg (1tablet) once daily after supper. Before and4weeks,8weeks,12weeks after the treatment, we performed follow-ups to observe clinical manifestations and adverse reactions, as well as testing the glycosylated hemoglobin A1c level (high-performance liquid chromatography), fasting and2-hour postprandial plasma glucose level (Glucose oxidase method, reagents bought from Kehuadongling biotechnological company), insulin level (radioimmunoassay), serum lipid (fully automatic biochemical analyzer TBA-40FR, product of TOSHIBA corp.,Japan), hepatic and renal function, electrocardiogram, blood pressure, body mass index (BMI)=weight (kg)/height (cm)2,insulin resistance index (HOMA-IR)=Fasting plasma glucose (FPG, mmol/L) X Fasting insulin (FINS, mIU/L)/22.5, β-cell function (HOMA-β)=20X Fasting insulin (FINS, mIU/L)/(Fasting plasma glucose (FPG, mmol/L)-3.5)(%), lasted for12weeks. All of the data were analysed by SPSS17.0statistical software package and the significantly test standard is a=0.05.Results1. During observation,3patients out of60dropped out, among which a male and two females, expulsion rate was5%due to one case of poor blood glucose control forced to adopt insulin treatment and one lost follow-up while one patient of accidental injury. There were57patients included,29in group A and28in group B.2. Baseline data of selected objects in two groups, such as the gender composition ratio, body mass index, age, blood pressure, fasting and2-hour postprandial blood glucose and insulin level, triglyceride, cholesterol, HOMA-IR, HOMA-β showed no significant difference and was thus comparable.3. Adverse drug reactions:3cases of hypoglycemia occurred, including1in group A and2in group B; a total of4cases of gastrointestinal reactions (nausea and mild diarrhea); no case of lactic acidosis was observed.4. After medication, weight、FPG、2hPG、F-Ins、HbAlc、TG、TC、HOMA-IR decreased, the β-cell function increased when compared to before using the medicine, but the comparison showed no significant difference.5. Whether morning or evening taking metformin (Glucophage) combined with sulfonylurea (gliclazide modified-release tablet, Diamicron) could effectively decreased the blood glucose; and also the fasting plasma glucose (FPG), fasting insulin (F-Ins), the glycosylated hemoglobin A1c level (HbA1c), triglycerides (TG) declined decreased with statistical significance (P<0.05or P<0.01) when compared to prior treatment; body weight reduced, the level of cholesterol (TC) decreased, islet beta cell function increased, but showed no significant difference (P>0.05). Conclusions1. Taking metformin after breakfast or after supper did not show statistically difference in aspects such as blood glucose, weight, plasma lipid, insulin resistance.2. The combination of metformin and sulfonylurea (gliclazide modified-release tablet, Diamicron) could effectively decrease fasting and postprandial blood glucose, glycosylated hemoglobin, plasma lipid improve islet beta cell function.