Mini Health Technology Assessment of Repaglinide and Naglinide / 中国药房

OBJECTIVE：To provid e reference for hospital decision-maker to select and use repaglinide and naglinide reasonably. METHODS ：Through reviewing literautre ，guideline and instruction ，full score system was estalished for comunni- cation between pharmacists and physicians ；from the aspects of clinical necessity ，effectiveness，safety，economy，medical insu- rance attribute ，essential medicine attribute ，original research attribute ，drug packaging attribute ，drug market and enterprise attributes，the Mini health technology assessment （Mini HTA ）was carried out for repaglinide and nateglinide ，and scored on the basis of weight value. RESULTS ：Repaglinide and naglinide ’s final score were 77 and 74，respectively. For type 2 diabetes，both of them could reduce postprandial blood glucose ，and had less side effect and good safety. They were both included in the medical insurance list. Both of them were original varieties ，easy to store and had a long period of validity. Although they were expensive in the treatment of type 2 diabetes，their manufacturers had a good reputation and were widely used in the world ，which was a good choice for patients with type 2 diabetes. But they were different to certain extent ；repaglinide could be used in patients with poor renal function [eGFR ＜30 mL/min] without dose adjustment ；nateglinide should be adjusted according to eGFR for renal excretion. Repaglinide was essential medicine but nateglinide wasn ’t；repaglinide didn ’t need shading storage but nateglinide did. In addition ， a variety of liver drug enzyme inducers or inhibitors may interact with the two drugs ，and special groups should be used with. CONCLUSIONS ：Mini HTA provide reference for the selection and rational use of repaglinide and nateglinide ；patients with type 2 diabetes can select suitable drug according to their own conditions and needs. When combined with other drugs ，blood glucose should be closely monitored to prevent the occurrence of hypoglycemia.

Design And Evaluation Of Buoyant Matrix System Of Nateglinide

The objective of the present study was to develop and optimize a buoyant tablet of Nateglinide to prolong the gastric residence time leading to reduce dose frequency which is an effective drug in the treatment of type II diabetes. The tablets were prepared by wet granulation technique using chitosan as a natural polymer in different ratios with sodium bicarbonate as gas generating agent. The compatibility of Nateglinide and all excipients were confirmed by FTIR spectroscopy. Pre-compression properties of granules are found within the prescribed limits and indicated good flow property. The tablets were evaluated for physical characteristics had shown that all of them comply with specifications of official pharmacopoeias. An optimized tablet formulation (F7) had less buoyancy lag time of 37 sec, total floating time of >12 hrs and higher the drug content of 100.16% and release of Nateglinide was 97.27 % after the end of 12 hours. From the kinetic modeling results, the drug release was Fickian diffusion controlled and followed zero order kinetics.

Correlation between Plasma Concentration of Nateglinide and Clinical Efficacy in Newly Diagnosed Type 2 Diabetes / 中国药师

Objective:To study the correlation between plasma concentration and clinical efficacy in newly diagnosed type 2 diabe-tes treated with nateglinide. Methods:On the basis of diet control and exercise, 73 cases of newly diagnosed type 2 diabetes received nateglinde therapy for 2 months. Adverse events were routinely monitored during the therapy. Fasting blood glucose(FBG), 2h post-prandial blood glucose(2h-PG), fasting C-peptide(F-CP), 2h C-peptide(P-CP) and glycosylated hemoglobin (HbA1c) were ob-served before and after the treatment. LC-MS was used to determine the plasma concentration of nateglinide on the last day of treat-ment. Results:FBG, 2h-PG, HbAlc and P-CP after the treatment had significant changes when compared with those before the treat-ment (P0. 05). The difference in HbA1c and P-CP before and after the treatment both showed a significantly positive correlation with plasma concentration of nateglinide (P<0. 05). Conclusion:Nateglinide displays good clinical efficacy and safety in newly diagnosed type 2 diabetes, and its plasma concentration can be used to evaluate the pancreatic islets function and glucose-lowing effects.

Concentration Determination of Nateglinide in Rats'Plasma by UPLC and Study on Its Pharmacokinetics / 中国药房

OBJECTIVE:To establish a method for the concentration determination of nateglinide in rats'plasma and study its pharmacokinetic characteristics in rats in vivo. METHODS:UPLC was performed on the column of Acquity UPLC? BEH C18 with mobile phase of acetonitrile-10 mmol/L potassium dihydrogen phosphate buffer(41:59,V/V)at flow rate of 0.38 mL/min,with col-umn temperature of 35 ℃,detection wavelength of 210 nm and volume of 2 μL. 18 Wister rats were intragastrically administrated nateglinide 16 mg/kg. Blood sample 0.4 mL was taken from medial canthus before administration and after 10,20,30,45,60, 90,120,180,240,360,480 min of administration. The concentration of nateglinide in rats'plasma was determined;then DAS 2.1.1 software was used to calculate its pharmacokinetic parameters. RESULTS:Nateglinide showed good linear relationship in 0.05-6.4μg/mL(r=0.9993),lower limit of quantification was 0.05μg/mL;RSDs of inter-day(n=5),intra-day(n=3)and sta-bility (n=3) tests were lower than 10%;extraction recovery rate and method recovery rate were 78.71%-80.56%,91.78%-100.42%(RSD<10%,n=5),respectively. After rats were intragastrically administrated nateglinide,AUC0-8 h was (5.87 ± 2.32)μg·h/mL,AUC0-∞was(6.11±2.48)μg·h/mL,t1/2 was(1.72±0.55)h,tmax was(0.67±0.29)h and cmax was(3.34±1.23)μg/mL. CONCLUSIONS:The method is accurate,rapid with strong specificity,and can be used for the concentration determination of nat-eglinide in rats in vivo;nateglinide is absorbed and metabolized quickly in rats in vivo.

Interaction of mouse intestinal P-glycoprotein with oral antidiabetic drugs and its inhibitors.

Type 2 diabetes (T2DM) is a progressive insulin secretory defect accompanied by resistance to insulin, and thereby making glycemic control a major concern in the treatment of these patients. Oral drug administration, though a popular option for its non-invasiveness, suffer from poor bioavailability. It could be related to the efflux transport of intestinal P-glycoprotein (Pgp). In the present study, we explored the binding interactions of antidiabetic drugs i.e., sulfonylurea drugs (glimepiride, glipizide, glyburide) and rapid acting insulin secretagogues viz., nateglinide, repaglinide and rosiglitazone; and Pgp inhibitors i.e., Generation I (verapamil and tamoxifen), III (tetradrine and tariquidar), and natural inhibitors (fumagillin and piperine) in mouse Pgp model. Our results revealed that fumagillin piperine and verapamil possess maximum interaction energies with Pgp compared to antidiabetic drugs. These observations elucidate the role of fumagillin and piperine as potential natural compounds which could intervene in the efflux action of Pgp in extruding the antidiabetic drugs and may have implications for increasing efficacy of oral antidiabetic therapy.

Development and in vitro/in vivo evaluation of controlled release provesicles of a nateglinide-maltodextrin complex

The aim of this study was to characterize the provesicle formulation of nateglinide (NTG) to facilitate the development of a novel controlled release system of NTG with improved efficacy and oral bioavailability compared to the currently marketed NTG formulation (Glinate™ 60). NTG provesicles were prepared by a slurry method using the non-ionic surfactant, Span 60 (SP), and cholesterol (CH) as vesicle forming agents and maltodextrin as a coated carrier. Multilamellar niosomes with narrow size distribution were shown to be successfully prepared by means of dynamic laser scattering (DLS) and field emission scanning electron microscopy (FESEM). The absence of drug-excipient interactions was confirmed by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies. In vitro release of NTG in different dissolution media was improved compared to pure drug. A goat intestinal permeation study revealed that the provesicular formulation (F4) with an SP:CH ratio of 5:5 gave higher cumulative amount of drug permeated at 48 h compared to Glinate™ 60 and control. A pharmacodynamic study in streptozotocin-induced diabetic rats confirmed that formulation F4 significantly (P<0.05) reduced blood glucose levels in comparison to Glinate 60. Overall the results show that controlled release NTG provesicles offer a useful and promising oral delivery system for the treatment of type II diabetes.

Clinical evaluation on efficacy and safety of nateglinide in the treatment of type 2 diabetes / 中国基层医药

Objective To evaluate the efficacy and safety of nateglinide,a new antidiabetic agent,in the treatment of type 2 diabetes.Methods 276 patients with type 2 diabetes mellitus,in accordance with the table of random number method,were divided into the nateglinide group 138 cases,repaglinide group 138 cases.The nateglinide group was given 30 mg nateglinide,and repaglinide group was given 0.5 mg repaglinide,3 times a day,oral administration 15min before meal.12 weeks for one period of treatment.FBG,2h PBG,HbAlc and security index were detected before and after treatment.Results After treatment,FBG,2h PBG and HbAlc indexes in the two groups were lower than before treatment,the differences were statistically significant(all P ＜ 0.05).The differences were not significant compared between the two groups (all P ＞ 0.05).No serious adverse events occurred in two groups.Conclusion Nateglinide can effectively control fasting and postprandial blood sugar in patients with type 2 diabetes.It is safe and reliable and worthy clinical promotion.

The influence of nateglinide treatment of newly diagnosed patients with type 2 diabetes on the state of inflammatory response / 中国基层医药

ObjectiveTo investigate the influence of nateglinide treatment of newly diagnosed patients with type 2 diabetes on the state of inflammatory response. MethodsThe clinical data of 74 newly diagnosed patients with type 2 diabetes were retrospectively reviewed,and treated with nateglinide,before and after treatment,the fasting blood glucose (FBG), postprandial blood glucose 0.5h ( 0.5 hPG), 1 h postprandial blood glucose ( 1 hPG) ,2h postprandial blood glucose(2hPG) ,fasting insulin(FINS) ,0.5h postprandial insulin(0. 5hINS) ,postprandial 1h insulin( 1 bINS),2h postprandial insulin(2hINS),interleulin-2(IL-2) and C-reactive protein(CRP) levels were observed. ResultsAfter treatment,the FBG,0. 5hPG, 1hPG,2hPG, FINS,0. 5hINS, 1hINS,2hINS, IL-2 and CRP of patients were ( 8.0 ± 1.5) mmol/L,(12.0±1.8)mmol/L,(10.2 ± 1.3) mmol/L,(10.5 ±1.2) mmol/L,(168.2 ±11.5) pmol/L,(213.5±23.5) pmol/L,(197.0 ±21.5) pmol/L,(189.5 ±12.0) pmol/L,(14.0 ±1.5) μg/L, (13.5 ±1.5) mg/L,compared with( 10. 5 ± 1.0) mmol/L, ( 14. 5 ± 1.5) mmol/L, ( 12. 5 ± 1.4) mmol/L, ( 11.6 ±2.0) mmol/L,(180.7 ±12.0) pmol/L,(229.8 ±26.0) pmol/L,(218.5 ±23.0) pmol/L, (197.0± 14.5) pmol/L,(12.5 ±2.0) μg/L, (22.8 ±2.0) mg/L before treatment decreased significantly(t =11. 9293,9. 1785,10. 3561,4. 1115,6. 4696,4.0009,5. 8744,3. 4279,5. 2307,32.0006, all P ＜0. 05). There was no serious adverse events in treatment process. ConclusionNateglinide treatment of newly diagnosed patients with type 2 diabetes could significantly improve the patient's inflammatory response state,and there was no serious adverse events in treatment process.

Immunological characteristics and pancreatic β-cell function in first-degree relatives of type 1 diabetes mellitus / 中华内分泌代谢杂志

Oral glucose tolerance test(OGTT)was performed in 419 first-degree relatives(FDRs)of type 1 diabetes mellitus. GADA, IA-2A, and IAA were determined by radioligand assay, and the positive rates were 7.16%, 1.43%, and 1.26%, respectively. Intravenous glucose tolerance test(IVGTT)and nateglinide-OGTT were performed in 39 controls, 11 first-degree relatives with positive autoantibody(Ab+group), 14 ones with negative autoantibody(Ab-group)during 5-7 days.The first-phase insulin release(FPIR), area under insulin release during 0-10 min [AUC0-10] of IVGTT and the value of(ΔI30/ΔG30)of nateglinide-OGTT in Ab+group were lower than those of control and(2.75±0.37 vs 3.61±1.05)mU/mmol, all P＜0.05]. The 1st min insulin release in Ab+group was lower than that of Ab-group [(3.80±0.30 vs 4.52±0.70)mU/L, P＜0.05]. The HOMA-IR was higher in Ab-group than that in control group(2.92±1.04 vs 1.96±1.22, P＜0.05). The results suggest that the positivity rates of autoantibodies in FDRs of type 1 diabetes mellitus are very close to those of Caucasian. There exist insulin secretion defects in FDRs with positive autoantibody while insulin resistance in FDRs with negative autoantibody.

Effect of nateglinide or sequential treatment with metformin on glycemic stability in newly diagnosed type 2 diabetic patients / 中华内分泌代谢杂志

The effect of nateglinide or sequential treatment with metformin on glycemic stability in newly diagnosed type 2 diabetes was investigated. Thirty-four cases of newly diagnosed type 2 diabetes received nateglinide therapy, or sequential treatment with metformin according to fasting and postprandial blood glucose, and were classified into isolated nateglinide therapy group(n=14) and sequentially treated with metformin group(n=20). Glycemic stability, reflected by mean amplitude of glycemic excursions(MAGE) and HbA1C, was determined in all patients before and after therapy for three months. HbA1C and MAGE in two groups were all improved after treatment(P＜0.05). The therapy of nateglinide alone or combined with metformin can significantly improve glycemic stability in newly diagnosed type 2 diabetes.

Efficacy of nateglinide combined with metformin in patients with newly diagnosed drug-na(i)ve type 2 diabetes / 中华全科医师杂志

Objective To compare efficacy of nateglinide or acarbose combined with metformin in patients with newly diagnosed type 2 diabetes.Methods Ninety-six patients with newly diagnosed type 2 diabetes in Metabolic Diseases Hospital of Tianjin Medical University,were randomly to receive nateglinide combined with metformin (group A,n =46) or acarbose combined with metformin (group B,n =42) for four months.Drug dose was adjusted every two weeks.Before and after treatment,oral glucose tolerance test and insulin release test were performed to observe changes of their glucose tolerance,homeostasis model assessment for insulin resistance (HOMA-IR) ,insulin secretion function of β-cells and glucose disposition index (DI) in the two groups.Results After four-month treatment,six patients restored to normal glucose tolerance and 13 patients returned to impaired glucose tolerance (IGT) in group A and 12 patients restored to IGT in group B.Their HOMA-IR was markedly improved compared with baseline in both groups,decreased to 7.1 ± 1.3 from 8.6 ± 1.2 in group A and to 6.9 ± 1.7 from 8.6 ± 1.7 in group B ( P ＜ 0.05 ).Compared with group B,early insulin secretion ( LN△I30/△G30 ) obviously improved in group A [( 1.9 ±0.8) vs.(1.6±0.6) mU/mmol] (P＜0.05) and DI also increased (1.05±0.25 vs.0.89±0.21,P＜0.05 ).Conclusions Nateglinide combined with metformin can obviously restore early insulin secretion and improve insulin resistance in patients with newly diagnosed type 2 diabetes,thus facilitate restoration of their glucose tolerance.

Clinical application of nateglinide:a Chinese expert consensus / 中华内分泌代谢杂志

Impaired eady phase insulin secretion is an important reason for leading to postprandial hyperglycemia.Nateglinide is a rapid-acting insulin secretagogue,which reduces postprandial blood glucose of type 2diabetic patient by restoring early phase insulin secretion.The efficacy and safety have been fully verified by clinical administration and it is more widely used to treat type 2 diabetic patients.Both sulfonylureas and glinides were named insulin secretagogue agents and regarded as alternative first-line drugs in the 2010 Chinese Guideline for treatment of type 2 diabetes.AACE/ACE Consensus statement claimed that glinides would be one of the important choices after metformin.In order to further guide the clinical application of nateglinide,16 national specialists in the field of endocrinology and metabolism of China discussed,drafted,and edited this consensus.The current consensus combined clinical evidences at home and abroad.systematically reviewed and summarized tlle results of these studies about nateglinide.It will provide guiding recommendations and reference concerning how to reasonably and effectively use nateglinide in the clinical practice.

Comparison of the therapeutic effects between insulin glargine combined with nateglinide and continuous subcutaneous insulin infusion during intraoperative period in type 2 diabetic patients with fracture / 中华内分泌代谢杂志

To compare the effect of insulin glargine combined with nateglinide and continuous subcutaneous insulin infusion(CSII) during intraoperative period in type 2 diabetic patients with fracture. Both of the managements made blood glucose under control [fasting blood glucose(6.89±1.96)vs(6.75±2.33)mmol/L] in similar period [(3.6±1.6)vs(2.9±1.2) d,both P>0.05]. The mean blood glucose was lower in patients treated by CSII than that of the other group.

Expression of pancreatic ATP-sensitive K~+ channels in rats with chronic pancreatitis and drug interventions / 中华肝胆外科杂志

Objective To observe the expression of pancreatic K_(ATP) channels (Kir6.2/SUR1) in rats with chronic pancreatitis and explore the intervention of nateglinide on the changes.Methods Wistar rats were induced to suffer from chronic pancreatitis and then randomized into model group, nateglinide group and control group.Then OGTT of them were observed.RT-PCR was used to detect the expression of Kir6.2 and SUR1 mRNA, and western blot to detect the expression of Kir6.2 and SUR1 proteins.Results Model rats displayed impaired glucose tolerance (IGT).The expression of Kir6.2 and SUR1 in model group decreased significantly(P＜0.05), and nateglinide displayed up-reg-ulation to the expression in some degree.Conclusion The expression of pancreatic K_(ATP) channels in rats with chronic pancreatitis diminished, which might be the important mechanism of the development of pancreatogenic diabetes.Nateglinide can up-regulate the expression in some degree, which indicates that it may have latent effect of ameliorating the prognosis of patients with chronic pancreatitis.

A comparison of efficacy and tolerance of nateglinide and acarbose monotherapy in type 2 diabetes mellitns / 中华内科杂志

Objective To compare the efficacy and tolerability of nateglinide with those of acarbose in Chinese type 2 diabetes mellitus (T2DM) patients.Methods This multi-center,randomized,double-blind,parallel-arm study compared the efficacy and tolerability of nateglinide( 120 mg,3/d,n = 119) and those of acarbose( 100 mg,3/d,n = 118) during a 12-week treatment in T2DM patients uncontrolled by diet with glycosylated haemoglobin (HbA1c) 6.5% - 11.0% .Results Monotherapy with nateglinide (120 mg,3/d)or acarbose (100 mg,3/d)decreased HbA1c to a similar extent during 12-week treatment.The mean change from baseline to end-point in HbAlc was ( -0.90±0.98)% and ( -0.83±0.81 )% in patients receiving nateglinide and acarbose,respectively,with no significant difference between the two groups (P>0.05).The decrease in fasting plasma glucose (FPG)was similar between nateglinide and acarbose (P > 0.05).The mean change in 2-hour postprandial plasma glucose ( PG2h ) was ( - 1.45 ± 2.74) mmol/L and ( -2.20±2.21 ) mmol/L in patients receiving nateglinide and acarbose(P =0.0017).Body weight was significantly decreased in both groups at the end-point ( P < 0.05 ),although the decrease was more with acarbese than nateglinide [( -0.66±1.79)kg vs (-2.06±2.00) kg,P=0.0000].And the proportion of patients experiencing any presumed drug related adverse events was not significantly different between the two groups.Conclusions Nateglinide ( 120 mg,3/d) is effective and well tolerated in T2DM patients uncontrolled by diet,demonstrating similar HbA1c reductions as compared with acarbose (100 mg,3/d).

A Case of Sustained Hypoglycemia due to Nateglinide in a Maintenance Hemodialysis Patient / 대한신장학회지

The risk of development of hypoglycemia increases during glycemic control in end-stage renal disease (ESRD) patients. We report the case that an ESRD patient on maintenance hemodialysis has experienced sustained hypoglycemia with a nateglinide. A 73-year old male ESRD patient on hemodialysis was admitted with exertional dyspnea and increased liver function test. On the 4th day after admission, he had mental change with his blood glucose level of 41 mg/dL. His mental state improved promptly after intravenous injection of 25 g of glucose. To prevent rebound hypoglycemia 10% glucose solution was continuously infused and nateglinide was discarded. However, he has had recurrent hypoglycemic attacks until the 6th day after admission, and thereafter there was no further hypoglycemic attack. On the 5th day of admission, when there was second hypoglycemic attack, the fasting insulin level was 31.62 U/mL, indicating that hypoglycemia was accompanied by insulin hypersecretion. In conclusion, we suggest that nateglinide may provoke a severe and sustained hypoglycemia in an ESRD patient on maintenance hemodialysis and its use might be avoided.

Improvement of Synthetic Technology of Nateglinide / 中国药房

OBJECTIVE: To improve the synthetic technology of nateglinide so as to increase yield and promote industrial production.METHODS: The improvement was conducted from aspects of reagent,catalyst,crystal form transformation etc in which the sodium hydride reported in literature was substituted by sodium hydrate in cis-trans transformation,and phosphorus trichloride or phosphorus pentachloride was substituted by thionyl chloride for the chlorination,and PtO2 or Raney Ni was substituted by RuNiAlC as catalytic agent.In H form crystal form transformation,fine seed-crystal was obtained by low temperature crushing,which was added with seed-crystal to induce crystallization to obtain H form crystal.The structure of the crystal form of the product obtained using the improved technology was characterized and its yield was computed.RESULTS: The crystal form characterization results demonstrated that the product was H form crystal and its yield reached 72%,higher than that reported in literature(50%).CONCLUSION: The improved technology of nateglinide contributed to the increase of its yield;Therefore,this technology is suitable for industrial production.

Application of New Pathogenesis on the Drug Treatment of Diabetes

Patients with type 2 diabetes mellitus are associated with insulin resistance and/or impaired insulin secretion. Previous observations indicate that patients with type 2 diabetes tend to have an impaired insulin response after a glycemic load. Recently it has been reported that hyperglycemia after a glucose load is itself a risk factor for the development of cardiovascular complications in the absence of elevated fasting plasma glucose. There are several points to be addressed for the application of new pathogenesis to diabetes treatment. One of them is the association between postprandial hyperglycemia and mortality from cardiovascular diseases. For the management of postprandial hyperglycemia inhibitors ofglucosidase and rapidacting insulin secretagogues have beneficial effects. Alphaglucosidase inhibitors in combination with diet therapy ameliorate insulin resistance and reduce the blood sugar level. A rapidly acting insulin secretagogue, such as repaglinide, lowers postprandial glucose levels without asignificant gain of body weight. These drugs may protect pancreaticcells from postprandial glucose toxicity and prevent the progression of diabetes. Both metformin and thiazolidinedione derivative (TZDs) improve insulin resistance, the major pathogenetic background of type 2 diabetes, and decrease blood glucose levels without stimulating, insulin secretion. Metformin inhibits glucose output from the liver, while TZDs increase glucose utilization in the peripheral tissues. In addition, it has been indicated that these agents ameliorate the metabolic syndrome beyond lowering the glucose level. Molecular targets for these agents have recentl been revealed ; AMPactivated protein kinase for metfOrnin and adiponectin, while PPAR for TZDs that induce gene expression of adipocyte glycerol kinase and adiponectin. Insulin-sensitizing agents are clinically useful for obese diabetic patients with insulin resistance. However, periodical examinations are necessary to avoid serious adverse effects such as lactic acidosis, although rare, by metformin and liver injury by TZDs. The advantage of insulin therapy for type 2 diabetic patients is still controversial. However, in many intervention studies, the intensive insulin therapy provided promising effects on preventing cardiovascular diseases. Moreover, insulin has been shown to stimulate nitric oxide production by cultured endothelial cells and to suppress the expression of intercellular adhesion molecule1 at least in vitro. In view of this antiinflammatory effect, longterm insulin therapy may potentially have an antiatherogenic effect.

Comparison between efficacy of nateglinide and repaglinide in improving type 2 diabetes pancreatic ? cell function / 重庆医科大学学报

Objective:To compare the efficacy between nateglinide and repaglinide in improving type 2 diabetes pancreatic ? cell function.Methods:A double-blind,randomized clinical study was introduced to 46 patients with type 2 diabetes mellitus who were administrated with nateglinide or repaglinide for 12 weeks.Both in the 0 week and the 12th week concentration of the serum insulin,C-peptide and blood glucose,as well as plasma HbA 1c concentration,were measured respectively at preprandial 0 min and postprandial 30,60,120min.Homa-?index,insulin response to glucose(IRG)and the ratio of the area under curve between insulin and glucose(AUCi/AUCg)were computed for statistical analysis.Results:Compared with 0 week,the levels of blood glucose and plasma HbA 1c all dropped in both groups with statistical significance(P