| ObjectiveThe prevalence rate of type 2 diabetes in china increases by an annual growth rate of 0.1%. Therefore, the long-term effective control of blood glucose and prevention of chronic complications of diabetes using the limited health resources have become clinicians'topic research. Only 15% of patients with type 2 diabetes can achieve satisfactory control with dietetic therapeutics alone. Though,oral medication must be used for more than 90% patients, who have suffering from the type 2 diabetes over one year. Correct use of oral glucose-lowering drugs, which is benefit for long-term effective control blood sugar and reduce the complications, appears especially important.The observation on the efficacy and safety of fixed-dose metformin / glipizide in the treatment of type 2 diabetes is studied in this article. The treatment strategy for long-term effective control of blood glucose is also discussed.Methods:Forty cases of type 2 diabetes (male 17, female 23) come from the Second Hospital of Jilin University in the endocrine out-patient treatment of patients from August 2008 to November 2008. They were randomly divided into 3 groups according to 2:1:1 distribution. The three groups are the test group (metformin glipizide capsule), control group 1 (metformin) and control group 2 (glipizide). The observation period is 12 weeks. Initial medications for them are metformin glipizide capsule (metformin 250mg /glipizide 2.5mg) + analog drugs, Metformin capsules (metformin 250mg) + analog drugs and glipizide tablets (Glipizide2.5mg) + analog drugs respectively. The dose is one tablet each time and three times a day.Simulation drugs were not containing active ingredients. Take medicine with warm water after each meal. Four weeks later, patients whose fasting blood glucose is in the range of 7.0 ~ 13.0mmol/L must begin to take medicine double, six tablets each time. The patients whose fasting blood glucose is less than 7.0mmol/L can maintain the original dose; General information among the three groups have no significant difference (P> 0.05), with good comparability.Observation of patients before and after treatment: 1) efficacy indicators: FBG, PPG2h, HbA1c, INS0h. 2) safety indicators: analysis of medication compliance, vital signs and routine blood (WBC, RBC, HB, PLT), routine urine (GLU, PRO, KET, WBC, RBC), hepatic and nephrtic function (ALT, AST, TBIL, Cr, BUN), electrocardiogram and adverse events (including hypoglycemia events).Statistical analysis uses the statistical analysis software, SPSS13.0. Measurement data uses the mean±standard deviation, the use of t tests and the rank-sum test. Count data uses the Fisher's exact test. P <0.05 is statistically significant difference.Results12 weeks later, the FBG, PBG 2h and HbA1c of three groups all decreased. Especially, the test group decreased statistically significant (P <0.05).INS0h of three groups are slightly higher, but no significant inter-group differences in comparison. Among the three groups, the incidence of adverse events was no statistical difference. DiscussionInternational Diabetes Federation (IDF) proposed a modern treatment of diabetes include diet control, exercise therapy, blood glucose monitoring, drug treatment and health education of diabetes. Diabetic oral hypoglycemic drug is very important for prevention and treatment. Clinical practice proved that pure diet and exercise therapy are effective for only a few patients with type 2 diabetes, drug treatment is needed for most (90%) of the patients with type 2 diabetes.Insulin resistance (IR) and relatively insufficient secrete of insulin in pancreasβ-cells are important pathophysiological features for T2DM, suffering three stages of insulin resistance, impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) and diabetes.Generally speaking, patients have been in insulin resistance 7 to 10 years before the diagnosis of diabetes. Clinical diagnose exists macro vascular disease. Patients occurs abnormal blood glucose when the pancreaticβ-cells not secrete insulin sufficiently. Research from United Kingdom prospective diabetes study (UKPDS) shown that theβ-cell function of patients with newly diagnosed type 2 diabetes has already lost 50%. The contribution ofβ-cell dysfunction and insulin resistance on glucose homeostasis for different individuals is the theoretical basis for treatment.Metformin is one of the oral biguanides hypoglycemic agents. It promotes the self insulin antigenicity, improves insulin sensitivity, reduces the insulin resistance, the polyphagia and fat synthesis, maintain or lose weight, do not cause low blood sugar alone and have no hypoglycemic effect on normal person. So, it is widely used in clinical.Its mechanism for regulates blood sugar level are: improving the sensitivity of liver for insulin, inhibiting the glycogen decomposition, hepatic gluconeogenesis and glucose released into the blood, promoting the glucose uptake and utilization in muscle, intestinal and fat cells. At the same time, it can enhance the Signal transduction of insulin receptor via increasing the activity and gene expression of BLUT-4. Research from UKPDS proves that metformin, which can reduce the complications of diabetes, is the only oral hypoglycemic drugs to reduce the cardiovascular risk and macrovascular complications of diabetes. Metformin, both alone and in combination with other drugs, can improve the blood sugar and reduce the variety of cardiovascular risk factors for diabetic patients.The mechanism of Sulfonylurea hypoglycemic depends on the main target site for the ATP-sensitive potassium channel (KATP). It is clear now that promoting the closure ofβ-cell KATP is the main mechanism for the releasing of insulin. Sulfonylureas, as well as, glucose (through transit, phosphorylation, oxidative metabolism of ATP) can stimulate the pancreaticβ-cell insulin release through this mechanism. Besides the directβ-cell stimulation, sulfonylureas can also increase the peripheral glucose utilization 10% ~52% (averaged 29%). Although, there are other researchers consider that this effect may secondary to the improvement of glucose toxicity. Generally speaking, different sulfonylureas may have different levels of to insulin in inner, but most of them require a higher plasma concentration to perform this function. This may not have practical clinical significance.Results of this study indicate that after 12 weeks'treatment, the FBG, PBG 2 h, HbA1c of the three groups decreased. The fixed-dose metformin / glipizide decreased more significantly than single-drug treatment. This conclusion is consistent with previous research, which proves that the sulfonylurea in combination with biguanides can be more effective than single-agent therapy for controlling the blood sugar. The INS0h of three groups are slightly increased, but it has no significant inter-group differences in comparison. All of them exhibit well tolerance with drug-related adverse events, mainly mild low blood lining reaction, only two cases for the experimental group and one case for control group 1and 2 respectively, which is 10% incidence. Other individual adverse events exhibit one case of mild headache in control group 2 and one case of gastrointestinal system disorders in experimental group and control group 1. Drug combination may reduce the dose of each single component, which can avoid the side effect caused by excessive Pharmacy and bring good compliance.The fixed-dose metformin / glipizide, which rationally cooperates two drugs with different action mechanisms, a combination of the insulin resistance andβ-cell failure of the pathophysiology defects of type 2 diabetes, is effective and safety for controlling the blood glucose to standards. ConclusionThe fixed-dose Metformin / Glipizide are effective for type 2 diabetes treatment with good compliance, tolerance, and mild adverse reactions. We conclude that reasonable combination of hypoglycemic drugs provide a more effective, tolerance and compliance treatment strategy for patients who can not effectively control blood glucose to standard with simple diet or exercise control and single drug treatment.
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