DPP-4 inhibitor and alpha-glucosidase inhibitor equally improve endothelial function in patients with type 2 diabetes: EDGE study Treatment with the dipeptidyl peptidase-4 inhibitor vildagliptin improves fasting islet-cell function in subjects with type 2 diabetes. Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes. Patients with Type 2 Diabetes Mellitus failing on oral agents and starting once daily insulin regimen; a small randomized study investigating effects of adding vildagliptin Effects of Concomitant Administration of a Dipeptidyl Peptidase-4 Inhibitor in Japanese Patients with Type 2 Diabetes Showing Relatively Good Glycemic Control Under Treatment with a Sodium Glucose Co-Transporter 2 Inhibitor. Comparative Effectiveness of Dipeptidylpeptidase-4 Inhibitors in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison Twelve-week monotherapy with the DPP-4 inhibitor vildagliptin improves glycemic control in subjects with type 2 diabetes. Addition of Neutral Protamine Lispro Insulin or Insulin Glargine to Oral Type 2 Diabetes Regimens for Patients with Suboptimal Glycemic Control Mobile Diabetes Intervention for Glycemic Control Effect of two starting insulin regimens in patients with type II diabetes not controlled on a combination of oral antihyperglycemic medications. Treatment of Type I Diabetes with a Combination of Glyburide and Insulin The rationale for paired pre- and postprandial self-monitoring of blood glucose: the role of glycemic variability in micro- and macrovascular risk Endothelial function and insulin resistance in polycystic ovary syndrome: the effects of medical therapy. Impact of Visit-to-Visit Glycemic Variability on the Risks of Macrovascular and Microvascular Events and All-Cause Mortality in Type 2 Diabetes: The ADVANCE Trial Comorbidity, hypoglycaemia and appropriate selection of antidiabetic pharmacotherapy in diabetic patients with heart failure in clinical practice in Germany The impact of initiating biphasic human insulin 30 therapy in type 2 diabetes patients after failure of oral antidiabetes drugs. Glycemic Control in Diabetes: A Tale of Three Studies
Background Alpha glucosidase inhibitor ( GI ) attenuates postpr and ial hyperglycemia ( PPH ) and reduces the risk of cardiovascular events in patients with impaired glucose tolerance or type 2 diabetes .  Dipeptidyl peptidase 4 ( DPP-4 ) inhibitors also attenuate PPH . PPH is one of the factors leading to endothelial dysfunction which is an early event in the pathogenesis of atherosclerosis . Furthermore , DPP-4 inhibitors protect endothelial function through a GLP-1-dependent mechanism . However , the impact of these two types of drugs on endothelial dysfunction in patients with type 2 diabetes has not been fully eluci date d. We compared the effects of sitagliptin , a DPP-4 inhibitor , and voglibose , an alpha GI , on endothelial function in patients with diabetes . Methods We conducted a r and omized prospect i ve multicenter study in 66 patients with type 2 diabetes who did not achieve the treatment goal with sulfonylurea , metformin or pioglitazone treatment ; 31 patients received sitagliptin treatment and 35 patients , voglibose treatment . The flow-mediated dilatation ( FMD ) of the brachial artery was measured in the fasting state at baseline and after 12 weeks of treatment . The primary endpoint was a change in FMD ( ΔFMD ) from the baseline to the end of follow-up . The effects of sitagliptin and voglibose on FMD were assessed by ANCOVA after adjustment for the baseline FMD , age , sex , current smoking , diabetes duration and body mass index . Secondary efficacy measures included changes in HbA1c , GIP , GLP-1 , C-peptide , CD34 , lipid profile , oxidative stress markers , inflammatory markers and eGFR and any adverse events . Results ΔFMD was significantly improved after 12 weeks of treatment in both groups , and there was no significant difference in ΔFMD between the two groups . There were no significant differences in changes in HbA1c , GIP , GLP-1 , C-peptide , lipid profile , oxidative stress marker , inflammatory marker and eGFR between the two groups . Compared with voglibose , sitagliptin significantly increased the circulating CD34 , a marker of endothelial progenitor cells . Adverse events were observed in 5 patients in only the voglibose group ( diarrhea 1 , nausea 1 , edema 2 and abdominal fullness 1 ) . Conclusions Sitagliptin improved endothelial dysfunction just as well as voglibose in patients with type 2 diabetes . Sitagliptin had protective effects on endothelial function without adverse events . Trial registration registered at http://www.umin.ac.jp/ctrj/ under CONTEXT Dipeptidyl peptidase 4 ( DPP-4 ) inhibitors are proposed to lower blood glucose in type 2 diabetes mellitus ( T2DM ) by prolonging the activity of the circulating incretins , glucose-dependent insulinotropic polypeptide ( GIP ) and glucagon-like peptide 1 ( GLP-1 ) . Consistent with this mechanism of action , DPP-4 inhibitors improve glucose tolerance after meals by increasing insulin and reducing glucagon levels in the plasma . However , DPP-4 inhibitors also reduce fasting blood glucose , an unexpected effect because circulating levels of active GIP and GLP-1 are low in the postabsorptive state . OBJECTIVE The objective of the study was to examine the effects of DPP-4 inhibition on fasting islet function . DESIGN We conducted a r and omized , double-blind , placebo-controlled trial . SETTING The study was performed in General Clinical Research Centers at two University Hospitals . SUBJECTS Forty-one subjects with T2DM were treated with metformin or diet , having good glycemic control with glycosylated hemoglobin values of 6.2 - 7.5 % . INTERVENTION Subjects were treated with vildagliptin ( 50 mg twice daily ) or placebo for 3 months , followed by a 2-wk washout . Major Outcome Measure : We measured insulin secretion in response to iv glucose and arginine before and after treatment and after drug washout . RESULTS There were small and comparable reductions in glycosylated hemoglobin in both groups over 3 months . Vildagliptin increased fasting GLP-1 levels in subjects taking metformin , but not those managed with diet , and raised active GIP levels slightly . DPP-4 inhibitor treatment improved the acute insulin and C-peptide responses to glucose ( 50 and 100 % respectively ; P < 0.05 ) and increased the slope of the C-peptide response to glucose ( 33 % ; P = 0.023 ) . CONCLUSION Vildagliptin improves islet function in T2DM under fasting conditions . This suggests that DPP-4 inhibition has metabolic benefits in addition to enhancing meal-induced GLP-1 and GIP activity CONTEXT In response to a meal , glucagon-like peptide-1 ( GLP-1 ) and glucose-dependent insulinotropic peptide ( GIP ) are released and modulate glycemic control . Normally these incretins are rapidly de grade d by dipeptidyl peptidase-4 ( DPP-4 ) . DPP-4 inhibitors are a novel class of oral antihyperglycemic agents in development for the treatment of type 2 diabetes . The degree of DPP-4 inhibition and the level of active incretin augmentation required for glucose lowering efficacy after an oral glucose tolerance test ( OGTT ) were evaluated . OBJECTIVE The objective of the study was to examine the pharmacodynamics , pharmacokinetics , and tolerability of sitagliptin . DESIGN This was a r and omized , double-blind , placebo-controlled , three-period , single-dose crossover study . SETTING The study was conducted at six investigational sites . PATIENTS The study population consisted of 58 patients with type 2 diabetes who were not on antihyperglycemic agents . INTERVENTIONS Interventions included sitagliptin 25 mg , sitagliptin 200 mg , or placebo . MAIN OUTCOME MEASURES Measurements included plasma DPP-4 activity ; post-OGTT glucose excursion ; active and total incretin GIP levels ; insulin , C-peptide , and glucagon concentrations ; and sitagliptin pharmacokinetics . RESULTS Sitagliptin dose-dependently inhibited plasma DPP-4 activity over 24 h , enhanced active GLP-1 and GIP levels , increased insulin/C-peptide , decreased glucagon , and reduced glycemic excursion after OGTTs administered at 2 and 24 h after single oral 25- or 200-mg doses of sitagliptin . Sitagliptin was generally well tolerated , with no hypoglycemic events . CONCLUSIONS In this study in patients with type 2 diabetes , near maximal glucose-lowering efficacy of sitagliptin after single oral doses was associated with inhibition of plasma DPP-4 activity of 80 % or greater , corresponding to a plasma sitagliptin concentration of 100 nm or greater , and an augmentation of active GLP-1 and GIP levels of 2-fold or higher after an OGTT Background The addition of a DDP4-inhibitor to existing insulin therapy reduces HbA1c . However , no data exist about the addition of these agents at the beginning of insulin treatment in type 2 diabetes while this could especially be interesting because it is during this period that considerable residual beta cell function is still present . The benefit of such a strategy could be a lower insulin dose required for glycemic control . The hypothesis of our study was that adding a DPP4-inhibitor at the beginning of insulin treatment could lead to less exogenous insulin requirement , a reduction of hyperinsulinemia and side effects ( hypoglycemia and weight gain ) , less glucose variability and improvement of insulin and glucagon dynamics during a mixed meal test . Results In this small clinical trial ( trial registration NTR2022 ) 9 patients were r and omized to receive  vildagliptin  and 6 to receive placebo in addition to start of once daily insulin treatment . Unfortunately , due to a difficult inclusion , the preset sample size of 40 patients could not be met . Median units of insulin at the end of the study was 47 U in the placebo group and 34 U in the vildagliptin group . Median glycemic variability ( SD ) at the end of study was 2.1 in the placebo group and 1.5 in the vildagliptin group . Median weight gain at the end of study was 3 kg in the placebo and 0.5 kg in the vildagliptin group . Occurrence of hypoglycemia was low in both groups . Insulin , C-peptide , glucose and glucagon levels were comparable during mixed meal tests . Conclusions This small r and omized study did not have sufficient power to detect effects of the addition of vildagliptin to the start of once daily long-acting insulin . However in our opinion adding a DPP4-inhibitor , especially in this group remains a very interesting approach . This study could be used as a guidance for larger studies that are required to investigate the effects of this intervention on insulin requirements , glycemic variability , hypoglycemia and weight gain We conducted this study to determine whether additional administration of a dipeptidyl peptidase-4 ( DPP-4 ) inhibitor might provide further improvement of the glycemic control in Japanese type 2 diabetes patients showing relatively good glycemic control under treatment with a sodium glucose co-transporter 2 ( SGLT2 ) inhibitor . Five SGLT2 inhibitor ( luseogliflozin , dapagliflozin , tofogliflozin , empagliflozin and canagliflozin ) preparations and five DPP-4 inhibitor ( sitagliptin , vildagliptin , alogliptin , anagliptin and linagliptin ) preparations were used . The results showed that monotherapy with SGLT2 inhibitor produced significant decreases of the body weight and BMI , hemoglobin A1c ( HbA1c ) also decreased , but not to a significant extent . However , decreases of the serum aspartate aminotransferase ( AST ) , alanine aminotransferase ( ALT ) , γ-glutamyltransferase ( γ-GTP ) and uric acid were observed in this group . On the other h and , in type 2 diabetes patients treated concomitantly with a DPP-4 inhibitor and SGLT2 inhibitor , significant decrease of the HbA1c was observed , indicating the favorable effect of the concomitant therapy . The body weight and BMI decreased . As for the serum lipid profile , elevation of the serum HDL-cholesterol ( HDL-C ) was observed . Furthermore , AST , ALT , γ-GTP and uric acid decreased in the combined treatment group . Then , the therapeutic responses to concurrent administration with SGLT2 inhibitor of each of the 5 individual DPP-4 inhibitors used in this study were analyzed . The results showed that concomitant administration of sitagliptin , a DPP-4 inhibitor , with the SGLT2 inhibitor yielded the best results in terms of the lowering of the HbA1c and improvement of the serum lipid profile Objective To compare the safety and efficacy of the dipeptidylpeptidase-4 ( DPP-4 ) inhibitors in patients with type 2 diabetes and inadequate glycemic control . Design Systematic review of r and omized controlled trials ( RCTs ) , health economic evaluation studies , systematic review s , and meta-analyses , followed by primary Bayesian mixed treatment comparison meta-analyses ( MTCs ) , and secondary frequentist direct-comparison meta-analyses using a r and om-effects model . Outcomes were reported as weighted mean change from baseline , or odds ratio ( OR ) with 95 % credible interval . Data sources MEDLINE , MEDLINE In-Process , EMBASE , and BIOSIS via Dialog ProQuest ; Cochrane Central Register of Controlled Trials and Cochrane Data base of Systematic Review s via EBSCO ; four diabetes and two technical congress abstract s ; and health technology assessment organization websites . Eligibility criteria Patients with type 2 diabetes and inadequate glycemic control receiving any pharmacological anti-diabetic treatment . Data extraction and analysis Title/ abstract s were review ed for eligibility , followed by full-text review of publications remaining after first pass . A three-person team filtered articles and an independent review er checked a r and om selection ( 10 % ) of filtered articles . Data extraction and quality assessment of studies were also independently review ed . Five DPP-4 inhibitors ( alogliptin , linagliptin , saxagliptin , sitagliptin , and vildagliptin ) were compared via meta- analysis ( where data were available ) as monotherapy , dual therapy ( plus metformin , sulfonylurea , pioglitazone , or insulin ) , and triple therapy ( plus metformin/sulfonylurea ) . Results The review identified 6,601 articles ; 163 met inclusion criteria and 85 publications from 83 RCTs contained sufficient or appropriate data for analysis . MTCs demonstrated no differences between DPP-4 inhibitors in mean change from baseline in glycosylated hemoglobin ( HbA1c ) or body weight , or the proportions of patients achieving HbA1c < 7 % or experiencing a hypoglycemic event , apart from in patients on alogliptin plus metformin , who achieved HbA1c < 7 % more frequently than those treated with saxagliptin plus metformin [ OR 6.41 ( 95 % CI 3.15–11.98 ) versus 2.17 ( 95 % CI 1.56–2.95 ) ] . Conclusions This systematic review and MTC showed similar efficacy and safety for DPP-4 inhibitors as treatment for type 2 diabetes , either as monotherapy or combination therapy UNLABELLED Inhibition of dipeptidyl peptidase-4 enhances the activity of incretin hormones , improving glycemic control in subjects with type 2 diabetes . This twelve-week r and omized , double-masked , placebo-controlled study assessed the efficacy and tolerability of the specific and potent oral dipeptidyl peptidase-4 inhibitor , vildagliptin ( 25 mg , bid , n=70 ) VS . placebo ( bid , n=28 ) in previously diet-treated subjects with type 2 diabetes . St and ardized meal tests were performed at baseline and endpoint . The between-group difference in adjusted mean change in HbA1c from baseline to endpoint was - 0.6 + /- 0.2 % ( p=0.0012 ) for the whole cohort ( baseline 8.0 % ) and -1.2 % for subjects with baseline HbA1c 8.0 - 9.5 % . Fasting glucose and mean pr and ial glucose were reduced by 1.1 + /- 0.4 ( p=0.0043 ) and 1.9 + /- 0.5 mmol/l ( p < 0.0001 ) , respectively . The between-group differences in corrected insulin response at peak glucose and mean pr and ial C-peptide were + 0.06 + /- 0.02 ( p=0.0258 ) and + 0.10 + /- 0.03 nmol/l ( p=0.0031 ) , respectively . Vildagliptin had no effect on fasting lipid levels or body weight . The incidence of adverse events was similar in subjects receiving placebo ( 71.4 % ) and vildagliptin ( 55.7 % ) . CONCLUSION monotherapy with vildagliptin is well tolerated and improves glycemic control in diet-treated subjects with type 2 diabetes . Concomitant improvements in beta-cell function were also observed . Subjects with higher baseline HbA1c levels showed greater response Context Bedtime insulin is a common strategy for improving glycemic control when type 2 diabetes is poorly controlled with oral agents . Insulin glargine acts longer and without peaking , so it achieves similar glycemic control with less hypoglycemia than neutral protamine Hagedorn ( NPH ) insulin , at least during the initial months of treatment . Neutral protamine lispro ( NPL ) insulin is a another intermediate-acting insulin with pharmacokinetics similar to those of NPH insulin , but 2 trials suggest better glycemic control with NPL . Contribution This trial compared the addition of bedtime insulin glargine or NPL insulin to oral medications in patients with poor control and found similar glycemic control and a similar number of hypoglycemic events in both groups over 36 weeks . Implication In this study sample , NPL insulin had no clinical advantage over insulin glargine . The Editors Glycemic control , preferably with hemoglobin A1c ( HbA1c ) levels less than 7 % , can substantially reduce the risk for microvascular and , to a lesser extent , macrovascular complications in patients with type 2 diabetes mellitus ( 14 ) . Maintaining such levels is now recommended internationally for clinical practice ( 57 ) but is difficult to achieve , despite the administration of escalating doses of oral antihyperglycemic drugs ( 810 ) . Secondary failure ( HbA1c level > 7 % ) occurs in 40 % to 60 % of patients after a few years of treatment with oral antihyperglycemic drugs ( 8) . Most patients eventually require insulin ( 8) , which usually is added when glycemic control with a regimen of oral antihyperglycemic agents becomes suboptimal ( 11 ) . Current approaches used by physicians vary on the basis of their experience , the availability and costs of medications , and stated or perceived patient preferences ( 12 , 13 ) . A single bedtime injection of long-acting insulin , such as neutral protamine Hagedorn ( NPH ) insulin , added while previous agents are continued is the preferred treatment option worldwide for patients with poorly controlled type 2 diabetes receiving oral drugs ( 12 ) . The basal insulin analogue glargine has a longer duration of action ( about 24 hours ) , with little or no discernible peak in circulating insulin concentration , than does long- or intermediate-acting human insulin preparations ( 14 ) . Neutral protamine Hagedorn insulin exhibits a peak in its timeaction profile 4 to 6 hours after injection , with a duration of action of about 12 to 14 hours ( 15 ) . The evidence from published clinical trials comparing the clinical efficacy of bedtime insulins ( glargine vs. NPH ) added to previous oral treatment have consistently found similar overall glycemic control and similar doses but less hypoglycemia with insulin glargine ( 1517 ) . However , the results of a recent study ( 18 ) comparing insulin glargine plus metformin with NPH insulin plus metformin found that the lower hypoglycemic rate seen at 12 weeks with insulin glargine was not seen at 36 weeks . In these trials ( 1518 ) , no allergic or local reactions were reported with either insulin glargine or NPH insulin . The cost of NPH insulin is less ( about one third ) than that of insulin glargine . Neutral protamine lispro ( NPL ) insulin is a protamine-based , intermediate-acting insulin formulation of the analogue insulin lispro . The pharmacokinetic characteristics of NPL insulin are similar to those of NPH insulin , with onset of action within 1 to 4 hours after injection , a peak at hour 6 , and a duration of action of about 15 hours ( 19 ) . In a clinical trial ( 20 ) comparing 2 basal bolus treatment schedules in patients with type 1 and type 2 diabetes , NPL has demonstrated better glycemic control and similar incidence of hypoglycemic events than did NPH . In theory , this may result in better outcomes in the setting of basal insulin therapy , although the potential usefulness of NPL insulin in combination therapy with oral antihyperglycemic drugs has never been studied . We aim ed to compare the clinical efficacy and safety of bedtime NPL insulin and insulin glargine when added to ongoing oral therapy in patients with type 2 diabetes who had suboptimal glycemic control while receiving stable doses of metformin and sulfonylurea .  To minimize the risk for nocturnal hypoglycemia , which may be enhanced by the concurrent administration of sulfonylureas ( 21 ) and may prevent adherence to the titration regimen , we permitted only metformin at dinner . Methods Design This open-label , r and omized , parallel , 36-week comparative study was done between January 2007 and March 2008 at Azienda Ospedaliera Universitaria , Second University of Naples , Naples , Italy , in accordance with the Declaration of Helsinki and with the institutional review board 's approval . This study consisted of a 4-week screening phase and a 36-week treatment phase . Men and women age 30 to 70 years , with duration of known diabetes greater than 2 years who received treatment with stable doses of metformin and sulfonylurea for at least 90 days , were selected for the study . Other inclusion criteria were body mass index less than 40 kg/m2 , HbA1c levels between 7.5 % and 10 % , and fasting plasma glucose ( FPG ) levels of 6.7 mmol/L or greater ( 120 mg/dL ) . Exclusion criteria were pregnancy or breastfeeding , previous use of insulin , other antihyperglycemic drugs or triple oral antidiabetic treatment within the previous 6 months , any investigational drug within the previous 3 months , sight-threatening retinopathy , use of agents affecting glycemic control ( systemic glucocorticoids and weight-loss drugs ) , unawareness of hypoglycemia or recurrent major hypoglycemia , anticipated changes in concomitant medication affecting glucose regulation , uncontrolled hypertension ( systolic blood pressure 180 mm Hg or diastolic blood pressure 105 mm Hg ) , and any clinical ly relevant somatic or mental diseases that may result in poor adherence to insulin regimens . To minimize the likelihood of including participants with late-onset type 1 diabetes , we excluded c and i date s with a positive test result for antiglutamic acid decarboxylase antibody or with fasting plasma C-peptide levels less than 0.76 ng/L ( < 0.25 pmol/L ) . We also excluded patients with abnormal laboratory test results , including liver enzymes ( alanine aminotransferase , aspartate aminotransferase , alkaline phosphatase ) greater than 3 times the upper limit of normal and serum creatinine levels greater than 123.8 mol/L ( > 1.4 mg/dL ) , history of illicit drug use , and poor adherence to the 8-point daily glucose profile measurement during the screening phase . Screening Phase During the screening phase , we obtained informed consent , recorded medical histories , did physical examinations , and determined whether patients met inclusion and exclusion criteria . Moreover , we drew blood sample s to measure HbA1c levels and analyzed complete hematologic and clinical chemistry . We trained participants to use the medical devices used in the study , either insulin pens or blood glucose meters ( OneTouch Ultra , Lifescan , Milpitas , California ) , and we also provided a complete 8-point , 24-hour glucose profile on the 2 consecutive days of the screening phase . We asked participants to discontinue the dinner sulfonylurea dose , if taken , and replace it with metformin , 850 mg . R and omization We r and omly assigned patients to either human NPL insulin ( Humalog NPL , Eli Lilly Italia , Sesto Fiorentino , Italy ) or insulin glargine ( Lantus , Sanofi-Aventis , Scoppitto , Italy ) by using a computer-generated , r and om-number sequence . Allocation was concealed in sealed study folders that were held in a central , secured location until after we obtained informed consent . The nurses who scheduled the study visits did not have access to the r and omization list . However , the staff members involved in the intervention had to be aware of the group assignment . Laboratory staff did not know the participants ' group assignments . Insulin was administered subcutaneously at bedtime . Both insulin formulations consisted of a cartridge containing 3 mL of either insulin preparation . Oral antihyperglycemic agents were continued at the pre study dosages , except for the replacement of dinner sulfonylurea with metformin . We did not give dietary advice beyond reinforcement of st and ard guidelines ( 22 ) . Intervention The initial bedtime insulin dose was 10 IU for all patients with the goal to achieve a target FPG level less than 5.6 mmol/L ( < 100 mg/dL ) in both groups . The insulin dose was titrated weekly , according to daily self-monitored fasting blood glucose measurements that provide values corresponding closely to laboratory measurements of FPG levels . The patients were taught to increase their insulin dose by 2 IU if FPG was greater than 5.6 mmol/L ( > 100 mg/dL ) and by 4 IU if FPG was greater than 10 mmol/L ( > 180 mg/dL ) on 3 consecutive mornings . Before the start of insulin therapy , and at weeks 12 , 24 , and 36 , we drew blood to measure full blood counts , electrolytes , creatinine levels , liver enzymes , and lipids . We recorded  insulin doses , self-monitored glucose profile , and any events associated with signs or symptoms of hypoglycemia in diaries . Continuous Glucose Monitoring We monitored subcutaneous interstitial glucose levels in 40 patients ( 20 for each group ) on an ambulatory basis over 3 consecutive days by using the second-generation continuous glucose-monitoring system ( Glucoday , A. Menarini Diagnostics , Florence , Italy ) . We did this before the addition of insulin and at the end of follow-up . We inserted the sensor at baseline and removed it on day 3 at mid-morning . We downloaded the data to a computer to evaluate glucose level variations , but calculations of these variations were limited to data obtained on days 1 and 2 to avoid bias due to both insertion and removal of the sensor and , thus , the insufficient stabilization of the monitoring system . We calculated the characteristic glucose level pattern of each patient by averaging the profiles obtained on study days 1 and 2 . We vali date d the records Background : Of adults with type 2 diabetes , 84 % take antihyperglycemic medication . Successful treatment requires active monitoring and medication dose adjustment by health providers . The objective of this study was to determine how a mobile-phone-based coaching system for diabetes management influences physician prescribing behavior . Method : This secondary data analysis is based on a cluster r and omized clinical trial that reported patients provided with mobile self-management had reduction in glycated hemoglobin ( HbA1c ) of 1.9 % over 1 year , compared to 0.7 % in control patients ( P < .001 ) . Participants were primary care patients with type 2 diabetes r and omized at physician practice level into a control group ( n = 55 ) and intervention group ( n = 62 ) . Main study measures were patients ’ medication records ( medication , dose , frequency , start and end date ) abstract ed at baseline and study end .  Antihyperglycemic medications  , including sulfonylureas or thiazolidinediones , and antihypertensive and antilipemic medications were analyzed . Results : A higher percentage of patients in the intervention group had modification and intensification of incretin mimetics during the 1-year study period ( 9.7 % vs 0.0 % and 8.1 % vs 0.0 % , both P = .008 ) . A higher percentage of patients in the intervention group had modification and intensification of metformin  ( 24.2 % vs 7.3 % , P = .033 ) . The overall difference in physician prescribing of oral antihyperglycemic medications was not statistically significant . Conclusions : Our results suggest mobile diabetes interventions can encourage physicians to modify and intensify antihyperglycemic medications in patients with type 2 diabetes . Differences in physician prescribing behavior were modest , and do not appear to be large enough to explain a 1.2 % decrease in HbA1c In an open-label , 24-week , parallel-group study , 135 patients inadequately controlled with oral antihyperglycemic medications ( OAMs ) were treated with maximally tolerated doses of metformin and glibenclamide for at least 8 weeks and then r and omized to bedtime neutral protamine Hagedorn ( NPH ) insulin plus maximally tolerated dose of glibenclamide BID ( glib/NPH group ) or insulin lispro mix 50 ( 50 % lispro , 50 % insulin lispro protamine suspension [ ILPS ] ) pre-breakfast and lispro mix 25 ( 25 % lispro , 75 % ILPS ) pre-dinner ( LM50/LM25 group ) ( both OAMs discontinued ) . The LM50/LM25 group had significantly lower 2-hour postpr and ial BG ( both meals combined ) compared with glib/NPH after 12 ( 11.70+/-3.40 mmol/L vs. 13.15+/-2.44 mmol/L , p=0.010 ) and 24 weeks ( 11.13+/-3.31 mmol/L vs. 14.46+/-2.93 mmol/L , p = 0.0001 ) . Both regimens significantly decreased HbA1c . The reduction was greater with LM50/LM25 ( -1.31+/-2 % vs. -0.5+/-1.6 % ; P=0.01 ) . At endpoint , the overall hypoglycemia rate increased with LM50/LM25 and decreased with glib/NPH compared with baseline ( 0.22+/-0.9 vs. -0.08+/-0.72 episodes/patient/30 days ; p = 0.037 ) . Treatment with LM50/LM25 compared with glib/NPH in patients with inadequate control on combined OAMs yielded better postpr and ial and overall glycemic control with a higher rate of hypoglycemia OBJECTIVE : To assess the ability of a combination of insulin and an oral hypoglycemic agent ( glyburide ) to improve the overall glycemic control in a population of patients with type I diabetes . DESIGN : R and omized , placebo-controlled , double-blind trial . SETTING : Community-based , university-affiliated , family medicine group . PATIENTS : Men and women between 18 and 68 years of age with type I diabetes . INTERVENTIONS : Subjects were observed and titrated on an insulin only regimen for 12 weeks ( phase I ) . Subjects were then r and omized to receive either placebo or glyburide 10 mg/d for an additional 12 weeks ( phase II ) . MAIN OUTCOME MEASURES : Glucose measurements were taken at breakfast , lunch , supper , and bedtime . Each patient also was followed sequentially for serum lipids , glycosylated hemoglobin , ( Hb A1c ) and daily insulin utilization . RESULTS : Average fasting blood glucose ( FBG ) measurements were significantly lower in the glyburide-treated group during phase II ( 9.22 ± 0.55 mmol/L ) compared with baseline ( 10.27 ± 0.93 mmol/L ) and phase I ( 10.41 ± 0.55 mmol/L ) . A decrease in the average Hb A1c concentration in the glyburide group was evident by week 4 and was sustained for the duration of the study . The average daily insulin dose rose significantly in the glyburide but not the placebo group compared with baseline . Total cholesterol , triglycerides , and low-density lipoprotein cholesterol did not change significantly in either group over the course of the study . High-density lipoprotein cholesterol increased significantly over baseline in the glyburide group during phase II . Several patients experienced dramatic improvements in glycemic parameters after the addition of glyburide to their insulin regimens . CONCLUSIONS : Improvements were observed in the FBG and Hb A1c measurements of this heterogeneous population of patients with type I diabetes after the addition of glyburide to their insulin regimens . The study failed to find consistent trends in glycemic control when evaluating mean changes in FBG measurements ABSTRACT Background : Decisions regarding diabetes management traditionally have been driven by the results of fasting plasma glucose measurement or measurement of glycosylated hemoglobin ( A1C ) , yet glycemic control remains far from optimal in many individuals with diabetes . Mounting evidence implicates glycemic variability , manifested predominantly as postpr and ial glycemic spikes , as a key factor in the development of macrovascular complications . Recent studies suggest that newer therapies specifically targeting postpr and ial hyperglycemia can significantly reduce postpr and ial glucose levels and improve overall glycemic control . Methods : A Medline search was performed using the term ‘ postchallenge ’ or ‘ postpr and ial ’ , together with glucose or diabetes . After excluding review articles and case studies , we review ed primary articles , meta-analyses , and references therein and selected those that best addressed this topic . Selection bias may be considered a potential limitation of this approach . Findings : Although not conclusively demonstrated by prospect i ve studies , a wealth of evidence suggests that postpr and ial hyperglycemia should not be ignored as an important target for preventing complications of diabetes . Conclusions : Improved detection and management of postpr and ial hyperglycemia and glycemic variability is necessary to optimize glycemic control . Meal-based self-monitoring of blood glucose ( SMBG ) has been shown to improve glycemic control as part of a comprehensive management strategy by helping patients underst and the effects of food choices , physical activity , and medications on blood glucose concentrations . SMBG can also help healthcare professionals recognize postpr and ial hyperglycemia , guide therapeutic adjustments and receive more timely feedback regarding medication changes . The arrival of new therapies that specifically target postpr and ial hyperglycemia offer healthcare professionals the opportunity to optimally manage diabetes OBJECTIVE To assess the interaction between insulin resistance and endothelial function and the optimal treatment strategy addressing cardiovascular risk in polycystic ovary syndrome . DESIGN R and omized controlled trial . SETTING Controlled clinical study . PATIENT(S ) Overweight age- and body mass index-matched women with polycystic ovary syndrome . INTERVENTION(S ) Six months metformin ( 1 g two times per day , n = 36 ) or oral contraceptive pill ( OCP ) ( 35 microg ethinyl E(2)-2 mg cytoproterone acetate , n = 30 ) . MAIN OUTCOME MEASURE(S ) Fasting and oral glucose tolerance test glucose and insulin levels , endothelial function ( flow-mediated dilation , asymmetric dimethylarginine , plasminogen activator inhibitor-1 , von Willebr and factor ) , inflammatory markers ( high-sensitivity C-reactive protein ) , lipids , and hyper and rogenism . RESULT ( S ) The OCP increased levels of glucose and insulin on oral glucose tolerance test , high-sensitivity C-reactive protein , triglycerides , and sex-hormone binding globulin and decreased levels of low-density lipoprotein cholesterol and T.  Metformin decreased levels of fasting insulin , oral glucose tolerance test insulin , high-density lipoprotein cholesterol , and high-sensitivity C-reactive protein . Flow-mediated dilation increased only with metformin ( + 2.2 % + /- 4.8 % ) , whereas asymmetric dimethylarginine decreased equivalently for OCP and metformin ( -0.3 + /- 0.1 vs. -0.1 + /- 0.1 mmol/L ) . Greater decreases in plasminogen activator inhibitor-1 occurred for the OCP than for metformin ( -1.8 + /- 1.6 vs. -0.7 + /- 1.7 U/mL ) . CONCLUSION ( S ) In polycystic ovary syndrome , metformin improves insulin resistance , inflammatory markers , and endothelial function . The OCP worsens insulin resistance and glucose homeostasis , inflammatory markers , and triglycerides and has neutral or positive endothelial effects . The effect of the OCP on cardiovascular risk in polycystic ovary syndrome is unclear OBJECTIVE There is no consensus on the importance of visit-to-visit glycemic variability in diabetes . Therefore , we assessed the effects of visit-to-visit variability ( VVV ) in HbA1c and fasting glucose on major outcomes in the ADVANCE ( Action in Diabetes and Vascular Disease : Preterax and Diamicron MR Controlled Evaluation ) trial . RESEARCH DESIGN AND METHODS ADVANCE was a factorial r and omized controlled trial of intensive glucose control and blood pressure lowering in patients with type 2 diabetes . VVV in the intensive glucose treatment group was defined using the SD of five measurements of HbA1c and glucose taken 3–24 months after r and omization . Outcomes were combined macro- and microvascular events and all-cause mortality occurring post 24 months . Sensitivity analyses were performed using other indices of variability and in the st and ard glucose treatment group . RESULTS Among 4,399 patients in the intensive group , an increase in VVV of HbA1c was associated with an increased risk of vascular events ( P = 0.01 ) and with mortality ( P < 0.001 ) : highest versus lowest tenth hazard ratio ( 95 % CI ) 1.64 ( 1.05–2.55 ) and 3.31 ( 1.57–6.98 ) , respectively , after multivariable adjustment . A clear association was also observed between VVV of fasting glucose and increased risk of vascular events ( P < 0.001 ; 2.70 [ 1.65–4.42 ] ) . HbA1c variability was positively associated with the risk of macrovascular events ( P = 0.02 for trend ) , whereas glucose variability was associated with both macro- and microvascular events ( P = 0.005 and P < 0.001 for trend , respectively ) . Sensitivity analyses using other indices , and patients in the st and ard glucose treatment group , were broadly consistent with these results . CONCLUSIONS Consistency of glycemic control is important to reduce the risks of vascular events and death in type 2 diabetes Background Patients with type 2 diabetes and heart failure are considered to be at high risk for hypoglycaemic complications . There is a considerable uncertainty with respect to the appropriate choice of antidiabetic pharmacotherapy in patients with type 2 diabetes and comorbid heart failure . Little is known about comorbidity , hypoglycaemia rates and selected pharmacotherapy in diabetic patients with heart failure in clinical practice . Methods DiaRegis is a prospect i ve registry in Germany including 3,810 patients with type 2 diabetes receiving antidiabetic treatment with oral mono or oral dual combination therapy in 2009/2010 . Only patients for which adjustment of pharmacotherapy  ( including the introduction of  insulin and GLP-1 analogues ) was deemed necessary were enrolled . We examined the differences in comorbidity , hypoglycaemia and choice of anti-diabetic pharmacotherapy  between diabetics with and without clinical heart failure in clinical practice in Germany . Results For 3,746 patients , data on the presence of heart failure were available , median ( IQR ) age 65.9 ( 57.6–72.8 ) years and 46.8 % were female . Patients with heart failure ( n = 370 ; 9.9 % ) were older , had a higher BMI , were less physically active , and had more cardiovascular risk factors and a substantial comorbidity . Glycaemic control was comparable between groups . Of the patients with heart failure , 76.8 % received metformin , 32.7 % sulfonylureas , 2.2 % glucosidase inhibitors , 4.3 % glinides , 6.2 % glitazones and 7.3 % DPP-4 inhibitors at baseline before adjustment of therapy . In multivariate analyses , patients with heart failure received less metformin ( odds ratio ( OR ) 0.58 , 95 % confidence interval ( CI ) 0.43–0.79 ) and sulfonylureas ( OR 0.70 , 95%CI 0.52–0.95 ) but not thiazolidinediones ( OR 1.22 , 95%CI 0.82–1.81 ) or other antidiabetic drugs . Hypoglycaemia was considerably more frequent in diabetic patients with heart failure than in those without ( OR 1.96 , 95%CI 1.47–2.61 ) . Conclusion Patients with type 2 diabetes and heart failure had a substantially increased comorbidity burden compared to patients without heart failure . They more often suffered from episodes of hypoglycaemia , especially those requiring medical assistance . The diagnosis of heart failure did not impact the choice of antidiabetic pharmacotherapy in patients with type 2 diabetes . There was no differential use of thiazolidinediones despite evidence discouraging their use in patients with heart failure . ZusammenfassungHintergrundPatienten mit Typ-2-Diabetes und Herzinsuffizienz haben ein erhöhtes Risiko für Hypoglykämien . I m klinischen Alltag besteht häufig Unsicherheit bezüglich einer adäquaten antidiabetischen Therapie bei Patienten mit zusätzlicher Herzinsuffizienz , und es existieren nur wenig Date n zur Komorbidität , zu Hypoglykämieraten sowie zur gewählten antidiabetischen Therapie von Patienten mit Diabetes und Herzinsuffizienz . Method ikDiaRegis ist ein deutsches prospektives Register . Von 313 niedergelassenen Ärzten wurden in den Jahren 2009/2010 insgesamt 3810 ambulant beh and elte Patienten mit Typ-2-Diabetes und antidiabetischer oraler Monotherapie oder oraler dualer Kombinationstherapie  eingeschlossen , bei denen der beh and elnde Arzt bei Aufnahme in das Register eine Anpassung der antidiabetischen Therapie vornahm ( inklusive der Gabe von Insulin oder GLP-1Analoga ) . Wir untersuchten Unterschiede in der Komorbidität , der Hypoglykämierate sowie der antidiabetischen Pharmakotherapie bei Patienten mit und ohne klinische Zeichen einer Herzinsuffizienz i m klinischen Alltag in Deutschl and .ErgebnisseBei 3746/3810 Patienten lagen Date n zur Herzinsuffizienz vor . Das mediane Alter betrug 65,9 Jahre ( Interquartilenabst and 57,6–72,8 ) ; 46,8 % der Patienten waren Frauen . Eine Herzinsuffizienz war bei 370 Patienten ( 9,9 % ) vorbeschrieben . Diese Patienten waren älter , hatten einen höheren BMI , waren körperlich weniger aktiv und hatten signifikant mehr kardiovaskuläre Risikofaktoren sowie deutlich mehr Begleiterkrankungen . Es f and en sich keinerlei Unterschiede in der Blutzuckerkontrolle , gemessen als HbA1c , Nüchtern- oder postpr and iale Plasmaglukose , zwischen Patienten mit bzw . ohne Herzinsuffizienz . Die Rate der Hypoglykämien in den 12 Monaten vor Einschluss in das Register war bei Patienten mit Herzinsuffizienz signifikant erhöht ( OR 1,96 ; 95%-KI 1,47–2,61 ) . Die Pharmakotherapie des Diabetes war bei Patienten mit Herzinsuffizienz zum Zeitpunkt des Einschlusses in das Register vor Therapieanpassung dominiert von Metformin ( 76,8 % ) , gefolgt von Sulfonylharnstoffen ( 32,7 % ) , Glukosidaseinhibitoren ( 2,2 % ) , Gliniden ( 4,3 % ) , Glitazonen ( 6,2 % ) und DPP-4-Inhibitoren ( 7,3 % ) . Nach Korrektur für die Unterschiede in den Patientencharakteristika mittels multivariater Analyse erhielten Patienten mit Herzinsuffizienz  seltener Metformin ( OR 0,58 ; 95%-KI 0,43–0,79 ) und Sulfonylharnstoffe ( OR 0,70 ; 95%-KI 0,52–0,95 ) . Keine Unterschiede zu Patienten ohne Herzinsuffizienz f and en sich bei Einsatz der and eren antidiabetischen Therapien , insbesondere auch nicht für Thiazolidindione ( OR 1,22 ; 95%-KI 0,82–1,81).SchlussfolgerungenIm klinischen Alltag in Deutschl and waren Patienten mit Typ-2-Diabetes und Herzinsuffizienz i m Vergleich zu Diabetikern ohne Herzinsuffizienz durch eine deutlich größere Komorbidität geprägt . Trotz gleicher HbA1c-Einstellung hatten diese Patienten signifikant mehr Hypoglykämien , insbesondere solche , die medizinische Hilfe benötigten , als Patienten ohne Herzinsuffizienz . Die Herzinsuffizienz hatte keinerlei Einfluss auf die Auswahl der antidiabetischen Therapie  des Typ-2-Diabetes i m Alltag in Deutschl and . Insbesondere Thiazolidindione wurden bei Patienten mit Herzinsuffizienz trotz der Hinweise aus r and omisierten Studien auf eine erhöhte Ereignisrate gleichermaßen eingesetzt BACKGROUND The present study evaluated the efficacy of biphasic human insulin 30 ( BHI 30 ) in type 2 diabetes patients who had failed in therapy with two or more oral antidiabetes drugs ( OADs ) . METHODS This open-label , nonr and omized , 4-month , multicenter , clinical observational study was conducted in Shanghai , China . A total of 660 insulin-naive type 2 diabetes patients with poor glycemic control ( glycosylated hemoglobin [ HbA1c ] ≥7.5 % ) , despite treatment with two or more OADs for more than 6 months , were recruited and received BHI 30 monotherapy or BHI 30 plus OAD(s ) ( metformin only , α-glucosidase inhibitor only , or both ) . RESULTS Among the 660 subjects , 644 completed the 4-month study . At the end of the study , the median level of HbA1c decreased by 2.0 % ( from 9.1 % to 7.0 % ) in the BHI 30 monotherapy group and also 2.0 % ( from 9.5 % to 7.3 % ) in the BHI 30 plus OAD group . More patients achieved the HbA1c < 7.0 % target in the BHI 30 monotherapy group than in the BHI 30 plus OAD(s ) group ( 47.9 % vs. 35.3 % , P=0.002 ) . Compared with the expenses of the prior treatment strategy , the median daily cost decreased by 39.8 % ( 4.5 yuan , Chinese RMB ) at the end point in the BHI 30 monotherapy group but increased by 20.0 % ( 2.2 yuan ) in the BHI 30 plus OAD(s ) group ( P<0.0001 ) . Moreover , patients in the BHI 30 plus OAD(s ) group had fewer minor hypoglycemic episodes than in the BHI 30 monotherapy group ( mean of 1.06 vs. 2.77 per patient per year , P<0.0001 ) . CONCLUSIONS Short-term BHI 30 therapy can improve glycemic control in insulin-naive type 2 diabetes patients after failure of two or more OADs . With higher baseline glucose level , the BHI 30 plus OAD(s ) group had lower pharmacoeconomic efficacy than the BHI 30 monotherapy group despite having fewer hypoglycemia events Much of the controversy at the American Diabetes Association Scientific Sessions , held 6–10 June 2008 in San Francisco , California , pertained to questions raised about the benefits of intensive glycemic control by three large clinical studies : the Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) trial , the Action in Diabetes and Vascular Disease ( ADVANCE ) trial , and the Veterans ’ Administration Diabetes Trial ( VADT ) . All three presented somewhat negative study results . David Goff ( Winston-Salem , NC ) discussed the ACCORD study design . The goal of ACCORD was to determine whether cardiovascular disease ( CVD ) event rates could be reduced by intensively treating three important risk factors ( hyperglycemia , dyslipidemia , and high blood pressure ) in a double 2 × 2 factorial design . For glycemia , the question of A1C < 6 vs. 7–7.9 % was addressed . Goff review ed previous studies that led to the decision to aim for the low A1C target . In the UK Prospect i ve Diabetes Study ( UKPDS ) , insulin and sulfonylurea treatment achieved a mean A1C level of 7 % , with 7.9 % in a control group . The 16 % CVD reduction just missed statistical significance . Metformin treatment in this study achieved a mean A1C level of 7.4 % with 8 % in a control group , associated with a significant 39 % CVD reduction . ( Goff did not mention that , compared with sulfonylureas alone , the other UKPDS metformin sub study showed that metformin with a sulfonylurea was associated with 96 , 60 , and 9 % increases in diabetes-related and all-cause mortality and in myocardial infa rct ion [ 1 ] . ) A nonsignificant CVD risk reduction of ∼50 % was seen in the Kumamoto study , while there was also a nonsignificant CVD risk increase of ∼50 % in the Veterans ’ Affairs Cooperative Study on Glycemic Control and Complications in Type II Diabetes ( VACSDM ) ; both studies showed A1C 7.1 % in the treatment group and 9.3–9.4 % in the control group . Analysis of a number of observational studies
Initial combination therapy with DPP-IV inhibitors more effectively reduced MAGE than stepwise add-on therapies ( p = 0.006 ) , although no differences in MAGE were found based on HbA1c values .
These findings indicate that DPP-IV inhibitors are promising alternatives for reducing GV in type 2 diabetes patients .
Glycemic variability ( GV ) has been an emerging target for preventing complications related to type 2 diabetes .
For reducing GV , DPP-IV inhibitors have shown effectiveness compared to other oral anti-hyperglycemic drugs ( OADs ) , but systematic evaluation has yet to be existed .