Endpoint HbA1c Research Articles

Characteristics of insulin-Na\xefve people with type 2 diabetes who successfully respond to insulin glargine U100 after 24\xa0weeks of treatment: a meta-analysis of individual participant data from 3 randomized clinical trials

BackgroundTo identify baseline/clinical characteristics associated with clinically meaningful responses to insulin glargine 100 U/mL (IGlar) in insulin-naive people with type 2 diabetes mellitus (T2DM).MethodsIndividual participant data were pooled from 3 randomized trials to compare baseline characteristics and clinical outcomes associated with 24-week response to IGlar in combination with non-insulin antihyperglycemic agents in participants with T2DM. Responders were defined as achieving endpoint HbA1c target < 53 mmol/mol (< 7%) and/or ≥ 11 mmol/mol (≥ 1%) HbA1c reduction from baseline.ResultsDifferences in baseline characteristics for responders versus nonresponders were higher HbA1c (99 vs 91 mmol/mol [9.1 vs 8.3%]; P < 0.001), higher fasting blood glucose (FBG; 10.4 vs 8.8 mmol/L [187 vs 159 mg/dL; P < 0.001), and fewer participants (94% vs 98%; P = 0.006) taking oral medications targeting postprandial blood glucose (BG). Most participants (80%) achieved one or both components of composite endpoint. 12-week response was a strong predictor of subsequent 24-week response (sensitivity, 85.9%; predictive positive value, 91.4%). At both 12 and 24 weeks, < 40% of responders and nonresponders reached target FBG ≤ 5.6 mmol/L (≤ 100 mg/dL). Responders at 24 weeks had higher incidence of hypoglycemia (total, 82.5% vs 70.4%; P < 0.001; nocturnal, 60.3% vs 50.5%; P = 0.002; documented symptomatic, 65.8% vs 55.6%; P < 0.001) than nonresponders.ConclusionsBaseline characteristics associated with response were identified. The strong predictability of 12-week response suggests that the magnitude of early HbA1c reduction should be considered when assessing response to IGlar. More aggressive IGlar titration may be reasonable for nonresponders and responders who have not reached FBG and HbA1c targets, taking into account other BG timepoints.

PDB9 - Characterizing the Clinical and Economic Burden of Type 2 Diabetes (T2DM) Patients on Multiple Daily Injections (MDI) of Insulin: A Systematic Literature Review

Evidence exists on demographics and costs of diabetes patients; however, data is limited on type 2 diabetes (T2DM) patients receiving a basal-bolus insulin regimen administered as multiple daily injections (>3 injections/day). The objective of the systematic literature review was to summarize the clinical and economic burden of T2DM patients using multiple daily injections (MDI) of insulin. A systematic literature review was conducted utilizing PubMed, the Cochrane library, and clinical trials.gov. Articles were included if they reported on clinical and/or economic burden of T2DM MDI patients. Articles were published after 1996, written in English. Key exclusions included: T1DM or mixed T1DM/T2DM populations (>10% T1DM); focus on non-insulin drugs or insulin pumps and studies enrolling <20 patients. Primary searches yielded 744 unique records, 330 full text articles were screened, and 66 met inclusion criteria. Fifty eight studies were primary observational (N=22) or interventional (N=36). Patients on insulin receiving >3 injections/day ranged from 23-36%. Mean demographic ranges included: age 49-73 years, weight 68-121kg, diabetes duration 6-17 years, and insulin duration 1-8 years. Comorbidities reported included hypertension (62-95%) and dyslipidemia (30-95%). Complications reported included neuropathy (29-59%) and retinopathy (19-22%). Total daily insulin doses ranged from 40-155 units/day; 0.7-2.4 U/kg/day. Mean baseline HbA1c ranged from 7.6-10.1% in observational and 6.9-10.3% in interventional studies. Patients achieving HbA1c <7% ranged from 8-16% in observational and 5-84% in interventional studies. Mean endpoint HbA1c ranged from 8.1-8.8% in observational; 6.4-8.6% in interventional studies. Total annual healthcare costs ranged from $20,553-$42,020; diabetes-related costs ranged from $8,180-$14,248. The findings of the systematic literature review suggest that T2DM patients on MDI had multiple comorbidities, microvascular complications, and substantial healthcare costs.

The Effects of Laparoscopic Sleeve Gastrectomy with Duodenojejunal Bypass on Japanese Patients with BMI < 35kg/m2 on Type 2 Diabetes Mellitus and the Prediction of Successful Glycemic Control.

Laparoscopic sleeve gastrectomy with duodenojejunal bypass (LSG-DJB) is a combination of sleeve gastrectomy and proximal intestinal bypass through duodenal exclusion. This technique has shown excellent weight loss and anti-diabetic effects in severely obese patients. In this retrospective study, we examined the clinical effects of LSG-DJB on mildly obese patients (body mass index (BMI) < 35kg/m2) with type 2 diabetes mellitus (T2DM) and analyzed factors contributing to the successful postoperative glycemic control. Seventy-two consecutive Japanese patients with T2DM with a BMI of < 35kg/m2 who underwent LSG-DJB in a single institution from September 2007 to March 2015 were included for the study. Weight loss, safety, and the impact on T2DM and metabolic syndrome were examined at 1year after surgery when weight loss reaches an expected plateau. In addition, pre- and postoperative factors between those who achieved diabetes remission (remitters) and non-remitters were compared. The follow-up rate at 1year after surgery was 93%. The mean percent total weight loss (%TWL) was 31.6 ± 8.8%, and the mean glycosylated hemoglobin (HbA1c) dropped from 8.9 ± 1.5 to 6.4 ± 1.0%. There were four early- and seven late-severe complications (grade III-A or more based on the Clavien-Dindo classification), which account for the 1-year morbidity rate of 15%. There was no mortality. The complete (HbA1c of < 6% without diabetes medication) and partial (HbA1c of < 6.5% without diabetes medication) remission of T2DM was achieved in 31 and 49% of the patients, respectively. Positive impacts were also observed on hypertension and dyslipidemia. Consequently, the ratio of those who achieved the composite endpoint (HbA1c of < 7%, low-density lipoprotein cholesterol < 100mg/dL, systolic blood pressure < 130mmHg) significantly increased from 4.2 to 22% (p = 0.003). Duration of T2DM and preoperative use of anti-hypertensive drugs were independent predictors of diabetes remission. Patients with a higher ABCD score were also at a higher rate of success in T2DM remission. LSG-DJB for T2DM patients with a BMI of < 35kg/m2 is a feasible and effective surgical method in achieving moderate weight loss and excellent improvement of glycemic control, metabolic syndrome, and cardiovascular risk although the T2DM remission rate was lower compared with severely obese individuals. Proper patient selection for candidates of the procedure is imperative to effectively predict poor responders.

Identifying insulin treatment responders with a composite measure: beyond Hba1c < 7% in patients with type 2 diabetes

Objectives: Many insulin-treated patients with type 2 diabetes (T2D) do not reach hemoglobin A1c (HbA1c) < 7%, but have clinically relevant HbA1c reductions. Using an integrated database (IDB) of 53 insulin lispro clinical trials and a real-world evidence (RWE) database of T2D patients initiating insulin therapy, an expanded HbA1c measure was used to identify responders to insulin therapy.Methods: Analysis included 4,908 patients (IDB) and 1,134 patients (RWE) with T2D treated with any insulin regimen with a baseline and ≥1 post-baseline HbA1c. Responders were defined as patients with endpoint HbA1c < 7% (cut point [CP]) and/or either ≥1% absolute (ABS) decrease, and/or ≥10% relative (REL) decrease in HbA1c from baseline. The percentage of responders with CP vs ABS and concordance between ABS and REL were calculated. As the ABS and REL measures were highly correlated (94%), the ABS measure was used to compare characteristics of responders and non-responders by age, diabetes duration, race/ethnicity, baseline HbA1c, and insulin regimen at 24 weeks.Results: In both databases, more responders were identified with ABS or REL (>62%) than CP (<41%). More ABS responders had a baseline HbA1c ≥ 9% and a shorter diabetes duration than non-responders. Basal insulin-treated patients in the IDB had 78.2% responders at 24 weeks, compared to 69.7% with basal/bolus or pre-mixed insulin (75.4%). Results were similar in the IDB and RWE.Conclusion: Composite HbA1c measures identified more patients with clinically meaningful responses to therapy than the broadly accepted HbA1c < 7% and may be useful in assessing clinical trials, clinical care, and quality measures.

Achieving the composite endpoint of HbA1c, body weight, and systolic blood pressure reduction with canagliflozin in patients with type 2 diabetes

Objective: In addition to achieving glycemic control, weight loss and blood pressure (BP) reduction are important components of type 2 diabetes mellitus (T2DM) management, as many patients with T2DM are overweight/obese and/or have hypertension. Canagliflozin, an SGLT2 inhibitor, has demonstrated improvements in HbA1c, body weight (BW), and systolic BP across a broad range of patients with T2DM. This analysis evaluated achievement of composite endpoints of HbA1c, BW, and systolic BP targets with canagliflozin versus placebo.Methods: This post hoc analysis evaluated the proportion of T2DM patients achieving the composite endpoint of HbA1c reduction ≥0.5%, BW reduction ≥3%, and systolic BP reduction ≥4mmHg with canagliflozin 100 and 300mg compared with placebo using pooled data from four 26-week, phase 3 studies (N = 2313; NCT01081834, NCT01106677, NCT01106625, NCT01106690). The proportion of patients achieving the composite endpoint of HbA1c <7.0%, BW reduction ≥3%, and BP <130/80 mmHg was also evaluated.Results: At week 26, greater proportions of patients met individual HbA1c, BW, and systolic BP targets with canagliflozin versus placebo. A greater proportion of patients treated with canagliflozin 100 or 300 mg versus placebo also achieved the composite endpoint of HbA1c reduction ≥0.5%, BW reduction ≥3%, and systolic BP reduction ≥4 mmHg at week 26 (21.1%, 25.3%, and 5.7%, respectively; odds ratios [95% CI] of 4.5 [3.1, 6.5] and 5.6 [3.8, 8.2]). A greater proportion of patients also achieved the composite endpoint of HbA1c <7.0%, BW reduction ≥3%, and BP <130/80 mmHg with canagliflozin 100 and 300 mg versus placebo (14.7%, 20.9%, and 3.3%, respectively; odds ratios [95% CI] of 5.2 [3.2, 8.4] and 8.4 [5.2, 13.5]). Canagliflozin was generally well tolerated, with a safety profile similar to that seen in other phase 3 studies.Conclusions: Patients with T2DM were more likely to achieve clinically important reductions in HbA1c, BW, and systolic BP with canagliflozin versus placebo.

Relationship of Glucose Variability With Glycated Hemoglobin and Daily Mean Glucose: A Post Hoc Analysis of Data From 5 Phase 3 Studies

The association of glucose variability (GV) with other glycemic measures is emerging as a topic of interest. The aim of this analysis is to study the correlation between GV and measures of glycemic control, such as glycated hemoglobin (HbA1c) and daily mean glucose (DMG). Data from 5 phase 3 trials were pooled into 3 analysis groups: type 2 diabetes (T2D) treated with basal insulin only, T2D treated with basal-bolus therapy, and type 1 diabetes (T1D). A generalized boosted model was used post hoc to assess the relationship of the following variables with glycemic control parameters (HbA1c and DMG): within-day GV, between-day GV (calculated using self-monitored blood glucose and fasting blood glucose [FBG]), hypoglycemia rate, and certain baseline characteristics. Within-day GV (calculated using standard deviation [SD]) was found to have a significant influence on endpoints HbA1c and DMG in all 3 patient groups. Between-day GV from FBG (calculated using SD), within-day GV (calculated using coefficient of variation), and hypoglycemia rate were found to significantly influence the endpoint HbA1c in the T2D basal-only group. Lower within-day GV was significantly associated with improvement in DMG and HbA1c. This finding suggests that GV could be a marker in the early phases of new antihyperglycemic therapy development for predicting clinical outcomes in terms of HbA1c and DMG.

Relationship Between Duration of Type 2 Diabetes and Effectiveness of DPP-4 Inhibitor Versus Sulfonylurea as Add-on Therapy: A Post Hoc Analysis.

IntroductionTo assess the impact of duration of type 2 diabetes on glucose-lowering effectiveness of the dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin versus sulfonylureas (SUs) in a real-life setting.MethodsData were extracted from the large 1-year, observational EDGE study (N = 45,868). Patients receiving either DPP-4 inhibitor or any SU as add-on to monotherapy were selected (N = 36,164). Impact of the disease duration on change in glycated hemoglobin (HbA1c) levels was evaluated by using a linear multiple regression model. Descriptive statistics assessed the proportion of patients achieving the composite endpoint (HbA1c <7.0%; 53.0 mmol/mol without hypoglycemia or weight gain), stratified by diabetes duration.ResultsAt baseline, the overall mean (±SD) type 2 diabetes duration was 5.4 ± 5.24 years, and HbA1c was 8.2 ± 1.33% (66.0 ± 14.5 mmol/mol). HbA1c lowering was directly proportional to the baseline HbA1c (−0.69 per unit; 95% CI −0.696, −0.681; p < 0.0001) and inversely proportional to the disease duration (0.01 per year; 95% CI 0.01, 0.013). There was an increased loss of β-cell function (less pronounced HbA1c drop with increasing disease duration) in patients treated with SU-based regimens (0.025; 95% CI 0.022, 0.027) compared with vildagliptin-based regimens (0.005; 95% CI 0.003, 0.007), with the mean adjusted difference being 0.10 (95% CI −0.122, −0.092; p < 0.0001). Consistently, a higher proportion of patients achieved the composite endpoint with vildagliptin over the diabetes duration (less than 2 to more than 10 years).ConclusionVildagliptin demonstrated less dependency on the duration of type 2 diabetes, whereas the effectiveness of SUs diminished faster with increasing duration of the disease in a real-life setting.FundingNovartis Pharma AG.

Which Patients Will Benefit from a Switch in Therapy from Premixed Insulin to Insulin Glargine plus Oral Antidiabetic Drugs? Further Analysis of the Lantus Registry Study.

IntroductionThis subgroup analysis of data from the 16-week Lantus Registry Study in China investigated the characteristics of patients with type 2 diabetes mellitus (T2DM) associated with clinical benefits of transitioning therapy from premixed insulin to insulin glargine (100 U/ml) plus oral antidiabetic drugs (OADs).MethodsThe modified intention-to-treat population of the Lantus Registry Study, comprising 1847 patients with T2DM, were included in the current subgroup analyses. Enrolled patients were divided into subgroups based on efficacy variables of endpoint glycated hemoglobin (HbA1c), endpoint fasting plasma glucose (FPG), and change in HbA1c from baseline. The baseline characteristics of those who did and did not achieve HbA1c <7.0% were compared, as were those with improvement, no change, or deterioration in HbA1c. Characteristics of patients who were unable to achieve HbA1c <7.0%, further grouped according to whether or not they achieved FPG ≤6.1 mmol/L, were also compared. Logistic regression analysis was used to identify factors associated with achieving HbA1c <7.0%.ResultsComparison between subgroups demonstrated that patients with endpoint HbA1c <7.0% were significantly younger, with a shorter duration of diabetes and lower baseline FPG, HbA1c, body mass index, and dose of premixed insulin than patients with endpoint HbA1c ≥7.0%. Logistic regression analysis revealed a negative correlation between baseline age, HbA1c, FPG, and duration of diabetes with achieving HbA1c <7.0%. When stratified according to change in HbA1c, the improvement group was younger, with higher baseline HbA1c and a greater number of patients with duration of diabetes ≤5 years. Three-quarters of patients unable to achieve HbA1c <7.0% also failed to reach FPG ≤6.1 mmol/L.ConclusionYounger patients with a shorter duration of diabetes and lower HbA1c, FPG, and premixed insulin dose following a switch in treatment to insulin glargine (100 U/ml) plus OADs from premixed insulin have greater potential to achieve HbA1c <7.0%. Poorly controlled patients with higher baseline HbA1c are most likely to experience an improvement in HbA1c following the switch in therapy. The majority of patients unable to achieve HbA1c <7.0% also failed to reach FPG ≤6.1 mmol/L, highlighting the importance of adequate titration of insulin glargine to achieve adequate FPG control, which can enable achievement of target HbA1c.FundingSanofi.

Evaluating drug cost per responder and number needed to treat associated with lixisenatide on top of glargine when compared to rapid-acting insulin intensification regimens on top of glargine, in patients with type 2 diabetes in the UK, Italy, and Spain

Objectives: This study investigated the cost per responder and number needed to treat (NNT) in type 2 diabetes mellitus (T2DM) patients for lixisenatide compared to insulin intensification regimens using composite endpoints in the UK, Italy, and Spain.Methods: Efficacy and safety outcomes were obtained from GetGoal Duo-2, a 26-week phase 3 trial comparing lixisenatide vs insulin glulisine (IG) once daily (QD) and three times daily (TID). Response at week 26 was extrapolated to 52 weeks, assuming a maintained treatment effect, based on long-term evidence in other T2DM populations. Responders were defined using composite end-points, based on an HbA1c threshold and/or no weight gain and/or no hypoglycemia. The HbA1c threshold was varied in sensitivity analyses. Annual treatment costs were estimated in euros (1 GBP = 1.26 EUR), including drug acquisition and resource use costs. Cost per responder was computed by dividing annual treatment costs per patient by the proportion of responders.Results: Lixisenatide was associated with the lowest cost per responder for all composite end-points that included a weight-related component. For the main composite end-point of HbA1c ≤7.5% AND no weight gain AND no symptomatic hypoglycemia, cost per responder results were: UK: 6,867€, 8,746€, and 12,410€; Italy: 7,057€, 9,160€, and 12,844€; Spain: 8,370€, 11,365€, and 17,038€, for lixisenatide, IG QD, and TID, respectively. The NNT analysis showed that, for every 6.85 and 5.86 patients treated with lixisenatide, there was approximately one additional responder compared to IG QD and TID, respectively.Limitations: A limitation of the clinical inputs is the lack of 52-week trial data from GetGoal Duo-2, which led to the assumption of a maintained treatment effect from week 26 to 52.Conclusions: This analysis suggests lixisenatide is an efficient economic resource allocation in the UK, Italy, and Spain.

Achievement of Composite Endpoint of HbA1c, Weight and Blood Pressure Reduction with Titrated Canagliflozin Added to Metformin+Sitagliptin in Patients with Type 2 Diabetes

Achievement of Composite Endpoint of HbA1c, Weight and Blood Pressure Reduction with Titrated Canagliflozin Added to Metformin+Sitagliptin in Patients with Type 2 Diabetes

Comparison of efficacy and safety of two starting insulin regimens in non-Asian, Asian Indian, and East Asian patients with type 2 diabetes: a post hoc analysis of the PARADIGM study.

ObjectiveThe objective of this study was to explore the efficacy and safety of insulin lispro mix 25 (25% insulin lispro and 75% insulin lispro protamine suspension [LM25]) or insulin glargine plus insulin lispro (G+L) in insulin-naïve patients with type 2 diabetes from different racial/ethnic groups.MethodsThree subgroups from the PARADIGM study were analyzed post hoc: non-Asian (n=130), Asian Indian (n=106), and East Asian (n=89).ResultsAll subgroups recorded glycated hemoglobin (HbA1c) reductions: non-Asian (LM25, −2.07%; G+L, −2.05%), Asian Indian (LM25, −1.75%; G+L, −1.60%), and East Asian (LM25, −2.03%; G+L, −1.76%); end point HbA1c values were higher in Asian Indians and East Asians than in non-Asians. Fewer Asian Indians (LM25, 43.2%; G+L, 29.2%) and East Asians (LM25, 37.5%; G+L, 36.1%) reached HbA1c <7% versus non-Asians (LM25, 51.7%; G+L, 48.1%); differences were not significant (P=0.12 and P=0.06, respectively). The mean total daily insulin dose (U/kg) for non-Asians was 0.67 (LM25) and 0.61 (G+L), for Asian Indians was 0.91 (LM25) and 0.90 (G+L), and for East Asians was 0.53 (LM25) and 0.59 (G+L). The ratio of mealtime to total insulin dose in the G+L arm for non-Asians was 0.19±0.23, for Asian Indians was 0.33±0.25, and for East Asians was 0.34±0.27. Overall incidence (%) of hypoglycemia in non-Asians was 94.1 (LM25) and 91.8 (G+L), in Asian Indians was 90.4 (LM25) and 88.5 (G+L), and in East Asians was 69.8 (LM25) and 77.3 (G+L).ConclusionAsian Indians showed least improvement in glycemic HbA1c reduction despite greater insulin use. East Asians and non-Asians achieved similar HbA1c reduction in the LM25 arm with a lower rate of hypoglycemia. Asians required more mealtime insulin coverage than non-Asians. This study added important insight into the effect of ethnicity on insulin treatment outcomes in patients with type 2 diabetes.

Canagliflozin provides greater attainment of both HbA1c and body weight reduction versus sitagliptin in patients with type 2 diabetes

ABSTRACTObjectives: To evaluate the proportion of patients with type 2 diabetes mellitus (T2DM) achieving reductions in both glycated hemoglobin (HbA1c) and body weight with canagliflozin, a sodium glucose co-transporter 2 inhibitor, versus sitagliptin over 52 weeks.Methods: Data were pooled from two, randomized, Phase 3 studies of canagliflozin 100 and 300 mg versus sitagliptin 100 mg as add-on to metformin, and canagliflozin 300 mg versus sitagliptin 100 mg as add-on to metformin plus sulfonylurea (N = 1856). The composite end points of change from baseline in both HbA1c <0% and body weight <0 kg, and attainment of HbA1c <7.0% and body weight reduction ≥5% at Week 52 were evaluated. Safety was assessed based on adverse event reports.Results: Canagliflozin provided reductions in HbA1c and body weight over 52 weeks versus sitagliptin. A greater proportion of patients had both HbA1c and body weight reductions with canagliflozin 100 and 300 mg versus sitagliptin 100 mg (67.7%, 72.6%, and 44.1%, respectively). Among patients with HbA1c and body weight reductions, more patients achieved the composite end point of HbA1c <7.0% and body weight reduction ≥5% with canagliflozin 100 and 300 mg versus sitagliptin 100 mg (18.9%, 18.3%, and 5.7%, respectively). Canagliflozin was generally well tolerated.Conclusions: A greater proportion of patients with T2DM achieved reductions in both HbA1c and body weight, and more patients with HbA1c and body weight reductions achieved HbA1c <7.0% and body weight reduction ≥5% with canagliflozin versus sitagliptin over 52 weeks.Clinical trial registration: www.ClinicalTrials.gov identifiers are NCT01106677; NCT01137812.

Clinical Effectiveness of Liraglutide in Type 2 Diabetes Treatment in the Real-World Setting: A Systematic Literature Review.

IntroductionIn clinical trials, liraglutide has proven to be an effective drug for the treatment of type 2 diabetes mellitus (T2DM). The real-world effectiveness of liraglutide has been investigated in numerous studies. The aim of this systematic literature review is to collate evidence on the real-world clinical effectiveness of liraglutide.MethodsA review of publications from Medline, EMBASE, the Cochrane Library, and conference proceedings was conducted to identify observational studies that assessed the clinical effectiveness of liraglutide in real-world clinical practice. This review was conducted according to the National Institute of Health and Care Excellence (NICE) guidance. No language or time limits were applied, except to the conference proceedings (2013–2015). Endpoints for data extraction were decided a priori. Study quality appraisal was done for full-text journal articles.ResultsOf 124 publications included in the review, 43 were full-text articles. Liraglutide significantly reduces glycated hemoglobin (HbA1c) within 6 months of initiating treatment (mean change in HbA1c from baseline: −0.9% to −2.2%; HbA1c <7.0%: 29.5–65.0%). The NICE composite endpoint (HbA1c reduction ≥1% and weight reduction ≥3%) was met in 16.9–47.0% of patients with liraglutide treatment. Liraglutide therapy led to a mean change in absolute weight from baseline of −1.3 to −8.65 kg. Liraglutide treatment was well tolerated in patients with T2DM. The rate of occurrence of hypoglycemia with liraglutide monotherapy was ≤0.8%. Hypoglycemia was more common in patients taking antidiabetic medications (0.0–15.2%) together with liraglutide. The beneficial glycemic and weight effect of liraglutide therapy in patients with T2DM was maintained for at least 12 months.ConclusionEvidence from observational studies reflecting real-world clinical practice demonstrates that liraglutide therapy improves glycemic control with a low risk of hypoglycemia, and is associated with significant weight loss in patients with T2DM. These observations are consistent with clinical trial findings.FundingNovo Nordisk A/S, Søborg, Denmark.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-016-0180-0) contains supplementary material, which is available to authorized users.

Lixisenatide improves glycemic outcomes of Japanese patients with type 2 diabetes: a meta-analysis.

BackgroundThe GetGoal-L-Asia and -S trials were multi-center trials conducted in 4 and 16 countries, respectively including Japan that evaluated the efficacy and safety of lixisenatide add-on treatment vs. placebo among patients with type 2 diabetes. The aims of this study were to determine the efficacy and safety of lixisenatide add-on treatment among Japanese patient groups.MethodsAll Japanese intent-to-treat patients with baseline and endpoint HbA1c measurements were included in the meta-analyses. Subgroup analyses were carried out for patients with low (<8 %) and high (≥8 %) baseline HbA1c levels, low (<25 kg/m2) and high (≥25 kg/m2) baseline body mass index (BMI), short (<10 years) and long (≥10 years) durations of diabetes, and for those <65 and ≥65 years of age.ResultsThe overall study population of Japanese type 2 diabetes patients included 143 patients (mean age: 59.0 years; 35 % female) treated with lixisenatide and 136 patients treated with placebo (mean age: 57.8 years; 32 % female). Among the subgroups, lixisenatide treatment vs. placebo was associated with greater change in HbA1c (Low HbA1c −0.80 %, p < 0.0001; High HbA1c −1.19 %, p < 0.0001; low BMI −0.88 %, p < 0.0001; high BMI −1.28 %, p < 0.0001; short diabetes duration −1.28 %, p < 0.0001; long diabetes duration −0.93 %, p < 0.0001; <65 years: −1.00 %, p < 0.0001; ≥65 years −1.24 %, p < 0.0001). Additionally, among the subgroups, lixisenatide treatment vs. placebo was associated with greater change in post-prandial glucose.ConclusionsFor Japanese type 2 diabetes patients lixisenatide may be an efficacious and safe add-on therapy leading to improved glycemic outcomes.GetGoal-L-Asia NCT01169779GetGoal-S NCT00713830

Evaluation of unmet medical need among Japanese patients with type 2 diabetes mellitus and efficacy of Lixisenatide treatment among Asian type 2 diabetes mellitus patients

AimsThis study determined the unmet medical need of basal insulin therapy among type 2 diabetes patients who participated in the ALOHA study. Also a meta-analysis of the GetGoal-Duo1, -L, and -L-Asia trials was conducted to examine the impact of lixisenatide add-on treatment to basal insulin therapy±OADs specifically among Asian type 2 diabetes patients. MethodsThe proportions of Japanese patients with an unmet need of diabetes management, defined as not achieving an HbA1c<7% despite having a fasting plasma glucose (FPG)<130mg/dL, and without an unmet need, defined as having an endpoint HbA1c<7%, regardless of FPG level, were determined for the ALOHA study population, which was conducted as a post-marketing survey for insulin glargine in Japan. For the meta-analysis, all Asian modified intent-to-treat patients with baseline and endpoint HbA1c measurements reported from the 3 GetGoal trials were included. ResultsAmong 1013 Japanese type 2 diabetes patients in the ALOHA study, 36% had an unmet need. In the GetGoal-Duo1, -L, and L-Asia trials, 237 Asian patients were treated with lixisenatide add-on treatment to basal insulin and 226 received placebo. Lixisenatide add-on treatment vs. placebo was associated with the following significant mean changes in efficacy outcomes at week 24: HbA1c: −0.6%, p=0.005; FPG: −13.3mg/dL, p=0.004; PPG: −101.4mg/dL, p<0.001; weight: −0.5kg, p=0.018; basal insulin dose: −1.6U, p<0.001. ConclusionsLixisenatide add-on treatment may provide a viable option to address the unmet need of basal insulin therapy among Asian type 2 diabetes patients.

Surgical Treatment of Diabetes: Making a Case for a Pragmatic Approach.

The development of type 2 diabetes mellitus (T2DM) is one of the most serious consequences of weight gain and obesity. Despite an understanding of this association by patients and their physicians, weight loss through diet and exercise, the typical lifestyle modifications recommended to break the yoke of diabetes that hangs on obese individuals, requires intensive interventions that can be difficult to maintain (1, 2). Moreover, lifestyle measures are generally inadequate in patients with severe obesity who are at particularly high risk of developing T2DM and its complications. Although developed primarily to facilitate weight loss, bariatric surgery has been noted to cause marked improvement in diabetes control (3). Emerging data have provided convincing evidence that bariatric surgery can produce rapid, effective, and sustainable remission of T2DM in addition to weight loss and is superior to nonsurgical interventions (3–7). Both the American Diabetes Association (8) and the American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery (9) have now expanded their treatment recommendations to include bariatric surgery as an option for individuals with morbid obesity, body mass index (BMI) 40 kg/m or 35 kg/m with comorbid conditions such as T2DM. Recently, the US Food and Drug Administration approved laparoscopic adjustable gastric banding (LAGB) for individuals with BMI of 30–34 kg/m and comorbidities. LAGB is a relatively simple bariatric procedure in which a saline-filled silicon band is fitted around the stomach near the esophageal junction. The level of gastric restriction imposed by the band can be adjusted by infusing saline through a sc port maintaining the desired level of gastric restriction. LAGB is the least invasive of the commonly used bariatric surgical procedures, with a perioperative mortality rate of approximately 0.05% (10). The safety, ease, and greater effectiveness for weight loss than what is usually obtained with lifestyle measures make the rationale for use of LAGB at lower levels of BMI, and raise the possibility of applying this procedure more widely in the treatment of T2DM. The outcomes of two previous randomized controlled studies have demonstrated that subjects receiving LAGB have superior weight loss and improvement in diabetes control relative to those getting medical or lifestyle management (4, 11). In this issue of the JCEM, Ding et al (12) add another study comparing the effectiveness of LAGB to medical/ lifestyle measures for the treatment of T2DM. They conducted a 12-month randomized, controlled, single-center trial comparing 23 diabetic subjects assigned LAGB with 22 subjects given intensive medical and weight management (IMWM) in a structured program based on previous successful regimens. Notably, they recruited diabetic patients without regard to ongoing treatment or duration of disease and with a broad range of diabetic control. In this sense, the study was arguably more pragmatic than some previous trials in that it involved a population reflective of the average diabetes practice. The average BMI for the study group was 36.5 3.7 kg/m; they had been diagnosed with diabetes for 9 5 years (10 6 in the surgery group and 8 4 in the control), and their glycated hemoglobin (HbA1c) was 8.2 1.2%. About 40% of the patients were on insulin (72% in the surgery group and 18% in the IMWM group). After 1 year, the primary endpoint (HbA1c 6.5% and fasting glucose 7.0 mmol/L) was achieved in 33% of the LAGB group and 23% of the IMWM group, a difference that did not differ statistically. HbA1c reduction over the course of the trial was similar between groups ( 1%), but weight loss was greater in the

Insulin Lispro with Continuous Subcutaneous Insulin Infusion is Safe and Effective in Patients With Type 2 Diabetes: A Randomized Crossover Trial of Insulin Lispro Versus Insulin Aspart

This study provides clinical information regarding the use of insulin lispro versus insulin aspart in continuous subcutaneous insulin infusion (CSII) in adult patients with type 2 diabetes mellitus (T2D). After a 2-week lead-in period, 122 subjects treated with CSII therapy were randomized to 32 weeks of treatment during 2 separate 16-week treatment periods (TPs) with crossover beginning with insulin lispro (n = 60) or insulin aspart (n = 62). Glycated hemoglobin A1c (HbA1c), total daily insulin dose, and weight were recorded at the end of TP1 and TP2. Adverse events (AEs) and hypoglycemic events (overall, documented symptomatic, nocturnal, or severe) were recorded throughout the TPs. Data were analyzed using statistical methods that accounted for repeated measurements. A total of 107 subjects completed the study; 7 discontinued in TP1 and 8 discontinued in TP2. Insulin lispro was noninferior to insulin aspart in endpoint (weeks 16 and 32) HbA1c over TP1 and TP2 combined. Total daily insulin dose, weight change, and incidence and rates of hypoglycemia were not statistically significantly different between treatments. One case of severe hypoglycemia and 1 of diabetic ketoacidosis was observed with insulin aspart. One case of severe infusion site abscess was noted with insulin lispro. Overall, both insulin lispro and insulin aspart were well tolerated with similar AEs reported. Insulin lispro and insulin aspart performed similarly after 16 weeks of treatment, with noninferiority for HbA1c and no significant difference in parameters measured. These findings indicate that insulin lispro and insulin aspart can both be used safely and effectively in patients with T2D using CSII.

Effectiveness and Tolerability of Second-Line Therapy with Vildagliptin Versus Other Oral Agents in Type 2 Diabetes (EDGE): Post Hoc Sub-Analysis of Bulgarian Data.

Objectives Metformin is an established first-line treatment for type 2 diabetes mellitus (T2DM) patients but intensification of oral anti-diabetic therapy is usually required over time. The effectiveness of diabetes control with vildaGliptin and vildagliptin/mEtformin (EDGE) study compared effectiveness and safety of vildagliptin and other oral anti-diabetic drugs (OAD) in 45,868 patients worldwide with inadequately controlled T2DM by monotherapy under real-life conditions. Here, we present effectiveness results for patients receiving vildagliptin (vildagliptin cohort) or another OAD (comparator cohort) add-on to monotherapy in Bulgaria.MethodsThe eligible diabetes patients inadequately controlled with current monotherapy were assigned to add-on treatment, which was chosen by the physician based on patient’s need. Effectiveness was assessed by glycated hemoglobin (HbA1c) drop and by means of a composite endpoint assessing the proportion of patients responding to treatment (HbA1c <7%) without proven hypoglycemic event and significant weight gain (>5%) after 12 months of treatment.ResultsIn total, 754 patients were enrolled in Bulgaria, 384 in the vildagliptin cohort and 369 in the comparator cohort. Mean HbA1c change from baseline was significantly higher with vildagliptin compared to the comparator (−1.35% in the vildagliptin cohort and −0.55% in the comparator cohort, P < 0.001). In the vildagliptin cohort, a higher proportion of patients reached the composite endpoint (HbA1c <7%, no hypoglycemic events, no weight gain) when compared to the comparator cohort (vildagliptin: 32.3%; comparator: 8.4%; P < 0.001). Overall, vildagliptin was well tolerated with similarly low incidences of total adverse events (3.4% versus 1.9% in the comparator group) and serious adverse events (2.3% versus 1.1% in the comparator group).ConclusionsIn real-life clinical practice in Bulgaria, vildagliptin is associated with a greater HbA1c drop, and a higher proportion of patients reaching target HbA1c without hypoglycemia and weight gain compared to comparator.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-014-0083-x) contains supplementary material, which is available to authorized users.

Comparison of efficacy of add-on therapy of vildagliptin versus pioglitazone among Type 2 Diabetes Mellitus patients inadequately controlled on dual therapy of metformin plus sulfonylurea

Objectives: To compare the efficacy of add on therapy of Vildagliptin versus Pioglitazone among Type 2 Diabetes Mellitus patients inadequately controlled on dual therapy of metformin and sulfonylureas. Methods: This was an open label prospective non randomized trial conducted on 50 patients attending Endocrinology Outpatient Department in a tertiary care hospital. Patients with type 2 Diabetes Mellitus (Type 2 DM) with age between 30 to 70 years of either gender, on dual oral anti-diabetic treatment (Metformin + Sulfonylurea) for at least last 3 months; HbA1c &gt;7% and &lt; 11%, BMI &gt;25 kg/m2, were included. Group I patients were started on pioglitazone (30 mg once daily) and those in group II started on vildagliptin (50 mg twice daily), in addition to their earlier treatment of metformin and sulfonylurea. Primary end point was change in HbA1c levels after 12 weeks from baseline and secondary outcomes were change from baseline in fasting plasma glucose (FPG) levels and percentage of patients with endpoint HbA1c &lt; 7% at 12 weeks. Results: A significant fall in HbA1c levels was seen in both the groups after 12 weeks of treatment with metformin, sulfonylureas and pioglitazone/ vildagliptin (p&lt;0.001), however the decrease in HbA1c levels at 12 weeks were not statistically different between the two groups (p = 0.16). Only four patients out of a total of 50, showed HbA1c &lt;7% at 12 weeks, out of which three were from pioglitazone and one patient from vildagliptin group. The FPG and random plasma glucose levels also decreased significantly in both the groups (p &lt; 0.001). No adverse effect was reported by the patients. Conclusion: Both vildagliptin and pioglitazone provided additional HbA1c lowering to that achieved with metformin and sulfonylurea. Vildagliptin demonstrates similar efficacy and safety to pioglitazone when added to metformin and sulfonylureas for three months. The clinical study is registered with Clinical Trials Registry of India, no. CTRI/2013/04/003582. Asian Journal of Medical Science, Volume-5(3) 2014: 77-81 http://dx.doi.org/10.3126/ajms.v5i3.9482

Initiation and Gradual Intensification of Premixed Insulin Lispro Therapy Versus Basal ± Mealtime Insulin in Patients With Type 2 Diabetes Eating Light Breakfasts

We compared two strategies initiating and intensifying insulin treatment and tested for noninferiority of premixed insulin to basal ± mealtime insulin analog in patients eating light breakfasts. This randomized, open-label, 48-week study compared two algorithms. Up to three injections of insulin lispro mix 25 and/or insulin lispro mix 50 (premix; premixed insulin lispro) or basal insulin glargine plus up to three injections of insulin lispro (basal+; glargine + insulin lispro) were used in type 2 diabetic patients uncontrolled with oral antihyperglycemic medication and consuming <15% daily calories at breakfast. The hypothesis was to test noninferiority of premix to basal+ for glycemic control measured by HbA1c after 48 weeks, assessed using ANCOVA with a 0.4% margin. Patients (n = 344; 176 [51%] females; mean [SD] age 54.3 [8.8] years; BMI 29.4 [4.6] kg/m(2); baseline HbA1c 9.02 [0.97]%) were randomized to premix (n = 171) or basal+ (n = 173). In the per-protocol analysis (n = 230), least squares means (95% CI) end point HbA1c were 7.40% (7.15-7.65) and 7.55% (7.27-7.82) in respective arms. Between-treatment difference was -0.14% (-0.42 to 0.13), with noninferiority met. Significantly more patients in premix achieved HbA1c targets of <7.0% compared with basal+ (48.2 vs. 36.2%; P = 0.024). Self-monitored blood glucose profiles, body weight changes, total insulin doses, and overall hypoglycemia (65 vs. 60%) were similar in premix and basal+ (P = 0.494), except nocturnal episodes (34.3 vs. 23.7%; P = 0.018) were more common in premix. Both intensive insulin strategies improved glycemic control; however, final HbA1c levels were seen above those achieved in previous treat-to-target trials, likely due to the inadequate insulin titrations and probably due to the complexity of tested insulin regimens. A higher percentage of patients achieved target HbA1c <7% with multiple premixed insulins, but this treatment resulted in more nocturnal hypoglycemia than a basal-bolus regimen.