Treatment Intensification In Patients Research Articles

Glycaemic control after treatment intensification in patients with type 2 diabetes uncontrolled on two or more non-insulin antidiabetic drugs in a real-world setting.

To assess glycaemic control after treatment intensification in patients with type 2 diabetes uncontrolled on ≥2 non-insulin antidiabetic drugs (NIADS). A retrospective cohort study, using electronic health records from the SIDIAP database (2010-2014), was conducted. Intensification was defined as the prescription of any new antidiabetic drug in patients treated with ≥2 NIADS and HbA1c >7%. The primary outcome was the absolute change in HbA1c 6-12 months after any intensification. Secondary analyses included the percentage of patients reaching HbA1c <7%, HbA1c <8%, and a reduction of HbA1c >1% after the first intensification. There were 21 241 intensifications in 15 205 patients with a mean (SD) HbA1c of 9.02% (±1.35). Insulin and dipeptidyl peptidase-4 inhibitors (DPP4i) were the most frequently added therapies. The mean baseline-adjusted HbA1c reduction was 0.78% (95% CI, -0.80 to -0.76), varying from -0.69% with DPP4i to -0.85% with glucagon-like peptide-1 receptor agonists while the addition of insulin was associated with a reduction >1%. After the first intensification, 48.9% of patients achieved HbA1c <8%, 16.2% HbA1c <7%, and 43.1% a reduction >1%. High previous HbA1c was positively associated with the reduction of HbA1c >1% [odds ratio (OR) 2.13 (95% CI: 2.05-2.21)], but inversely associated with the attainment of HbA1c <7% [OR 0.64 (0.61-0.67)] or < 8% [OR 0.63 (0.60-0.65)]. Older age, male gender, higher Charlson index, and short diabetes duration were associated with achievement of HbA1c <7%. Despite intensification, most patients failed the glycaemic goal of HbA1c <7%. The reduction depended mainly on preintensification HbA1c values, with small differences between drugs.

Predictors and Clinical Outcomes of Treatment Intensification in Patients with Type 2 Diabetes Uncontrolled on Basal Insulin in a Real-World Setting

To understand factors associated with intensification of basal insulin therapy and treatment impact on clinical outcomes in patients with type 2 diabetes (T2D). In this retrospective, observational study of the Practice Fusion electronic health record database, eligible patients were adults with T2D, ≥1 basal insulin prescription and office visit in the 6 months before a glycated hemoglobin A1c (A1C) test >7.0% (index date), and no other injectable prescriptions in the 12 months before the index date. Patients were categorized to intensifiers with injectables (rapid-acting insulin [RAI], glucagon-like peptide-1 receptor agonist [GLP-1 RA], or other injectables) or nonintensifiers with injectables (including no change, adding an oral antidiabetes drug, or changing basal insulin dose). Principal outcomes were A1C change, hypoglycemia incidence, and change in body weight. Among 14,653 patients, 2,121 (14.5%) and 12,532 (85.5%) were categorized as intensifiers and nonintensifiers with injectables, respectively. Compared with nonintensifiers, intensifiers were more likely to have an endocrinologist as the prescribing physician (odds ratio [OR], 2.52 [95% confidence interval (CI), 2.16 to 2.94]), hypertension (OR, 1.26 [95% CI, 1.08 to 1.47]), higher baseline A1C (OR, 1.22 [95% CI, 1.17 to 1.26]), obesity (OR, 1.17 [95% CI, 1.01 to 1.36]), and higher body mass index (OR, 1.02 [95% CI, 1.01 to 1.03]). In GLP-1 RA intensifiers, the baseline use of dipeptidyl peptidase-4 inhibitors increased the likelihood of intensification. GLP-1 RA intensifiers had equivalent glycemic control to RAI or other injectables, with a nonsignificantly lower risk of hypoglycemia and reduction in body weight. Addition of GLP-1 RA to basal insulin may be an effective strategy for overcoming clinical inertia with injectable therapy in patients with T2D. A1C = glycated hemoglobin A1c; BMI = body mass index; CI = confidence interval; DCSI = Diabetes Complications Severity Index; DPP-4 = dipeptidyl peptidase-4; EHR = electronic health record; GLP-1 RA = glucagon-like peptide-1 receptor agonist; ICD-9-CM = International Classification of Diseases-Ninth Revision-Clinical Modification; ICD-10-CM = International Classification of Diseases-Tenth Revision-Clinical Modification; OAD = oral antidiabetes drug; OR = odds ratio; RAI = rapid-acting insulin; SGLT-2 = sodium-glucose cotransporter-2; T2D = type 2 diabetes.

HbA1c, Weight, and Blood Pressure Changes Associated with Early vs. Late Treatment Intensification with Dapagliflozin in U.K. Primary Care Patients with Type 2 Diabetes

Early treatment intensification in patients with type 2 diabetes (T2D) is often required to achieve glycaemic control. Patients with T2D from the UK Clinical Practice Research Datalink, aged ≥18 years, initiating dapagliflozin between Nov 2012 and Aug 2016 and with prior oral T2D therapy (N=3,774) were included in this study. The relationship between early (2nd line) vs. later (≥3rd line) use of dapagliflozin and changes from baseline in HbA1c (≥1.0% absolute reduction), weight (kg) (≥5.0% relative loss) and systolic BP (≥2 mmHg absolute reduction) after 6-12 months were assessed with logistic regression models. Early use of dapagliflozin occurred in 25.2% patients (951/3774) vs. later use in 74.8% (2823/3774). Patients with later use were older [mean: 60.1 (SD 10.3) vs. 55.7 (SD 10.5) years], more likely to be male (61.6% vs. 55.3%), had T2D for longer [median 8.1 vs. 4.0 years] and higher CVD prevalence (13.9% vs. 11.2%). Patients with early and later use of dapagliflozin had similar baseline mean HbA1c levels [9.3% (SD 1.5) vs. 9.2% (SD 1.7)] and BP [134.2 (SD 14.2) vs. 135.0 (SD 14.6) mmHg]. Late users had lower BMI [mean 33.6 (SD 6.3) vs. 36.5 (SD 6.8) kg/m2] than early users. Early dapagliflozin users experienced mean (S.E) reductions of 1.6 (0.07)%, 3.8 (0.25)% and 3.0 (0.82) mmHg in HbA1c, weight and BP, respectively, vs. 1.0 (0.04)%, 4.6 (0.21)% and 3.1 (0.43) mmHg in later users. Compared to later dapagliflozin use, early initiation was associated with a greater likelihood of adjusted HbA1c reduction ≥1% (OR: 1.68, 95% CI: 1.15-2.45). Weight and BP reductions were observed with similar likelihood among early and late users (weight OR: 0.79, 95% CI: 0.54-1.14; BP OR: 0.87, 95% CI: 0.58-1.30). In conclusion, glycaemic benefits of dapagliflozin were greater in patients receiving it earlier in their treatment pathway. Weight and BP reductions were achieved with similar likelihood among early and later users. Disclosure J.P. Wilding: Other Relationship; Self; Astellas, AstraZeneca, Boehringer Ingelheim GmbH, Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi, Eli Lilly and Company, Orexigen Therapeutics, Inc., Merck &amp; Co., Inc. U. Rigney: Employee; Self; AstraZeneca. B.T. Blak: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. S.T. Nolan: Employee; Self; AstraZeneca. P. Fenici: Employee; Self; AstraZeneca. J. Medina: Employee; Self; AstraZeneca.

Glycaemic impact of treatment intensification in patients with type 2 diabetes uncontrolled with oral antidiabetes drugs or basal insulin.

SummaryAimsTo investigate the impact of treatment intensification (TI) on glycaemic outcomes in patients with type 2 diabetes with glycated haemoglobin A1c (A1C) ≥7% after ≥6 months of treatment with 2 oral antidiabetes drugs (OADs) or basal insulin (BI).Materials and MethodsData were extracted from the Optum administrative claims database from 1 January 2009 to 31 August 2015. Patients with TI ≤6 months after the first A1C ≥7% (index date) were compared with patients with no TI (NTI). TI included addition of OAD, GLP‐1 receptor agonist or premixed insulin in OAD and BI cohorts, addition of BI and/or bolus insulin in the OAD cohort and addition of bolus insulin or increasing BI dose in the BI cohort. Change from the index A1C value and hypoglycaemia events was compared at 12 months after TI after adjusting for confounders.ResultsA total of 3990/28 123 (14.2%) and 10 425/16 140 (65%) of eligible adults in the OAD and BI cohorts, respectively, underwent TI. These patients showed greater adjusted A1C change vs NTI patients (OAD cohort: −0.59% vs −0.25%; BI cohort: −0.30% vs −0.16%; P < .001 for both comparisons), but with higher hypoglycaemia rates (OAD cohort: odds ratio [OR] 1.68; P < .001; BI cohort: OR: 1.23; P = .004) at follow‐up.ConclusionsClinical inertia appears to be a significant issue in this population. Although associated with more frequent hypoglycaemia, these results demonstrate that timely TI improves A1C levels, highlighting the need for new and improved agents to effectively manage glycaemia while reducing hypoglycaemia risk.

Basal Insulin Intensification in Patients with Type 2 Diabetes: A Review.

As the number of people living with type 2 diabetes (T2D) continues to rise, managing their complex needs presents an increasing challenge to physicians. While treatment guidelines provide evidence-based guidance, they are not prescriptive—rather they emphasize individualization of management based on a patient’s clinical needs and preferences. Physicians, therefore, need to be fully aware of the advantages and disadvantages of the multiple and increasing treatment options available to them at each stage of the disease. The progressive nature of T2D means that treatment with basal insulin will become inevitable for many patients, while for some patients basal insulin alone will eventually be insufficient for maintaining glycemic targets. Recent guidelines recommend two basic approaches for intensifying basal insulin: the use of rapid-acting insulin, either as additional prandial injections or as part of premix (biphasic) insulin; and the addition of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to the insulin therapy, which can be administered via subcutaneous injection once or twice daily, or weekly depending on formulation. More recently, two fixed-ratio combinations of basal insulin and a GLP-1 RA that allow for once-daily dosing have been approved. Each of these approaches has potential benefits and drawbacks, particularly in terms of risk for hypoglycemia, weight change, convenience, and side effects. Understanding these differences is central to guiding patient and physician choice. This article discusses the rationale, advantages, disadvantages, and implementation of currently available strategies for basal insulin treatment intensification in patients with T2D.Funding: Sanofi US, Inc.

Individualised treatment targets in patients with type-2 diabetes and hypertension

AimPatients with type-2 diabetes mellitus (T2DM) are at high risk of cardiovascular events, accentuated in the presence of hypertension. At present, it is unclear to what extent the guidelines for the management of T2DM, advocating reduction in HbA1c levels to below target levels, are being adhered to in clinical practice.MethodsDIALOGUE was a prospective, observational, non‐interventional registry performed across multiple centres in Germany. Patients aged 18 years or older who had T2DM and hypertension for whom the treating physician considered blood glucose lowering medication as inadequate and/or not safe/tolerable and chose to add a further oral drug or switch drug treatment were included. Patients were assigned a treatment target HbA1c value (≤ 6.5% [strict]; > 6.5 to ≤ 7.0% [intermediate]; > 7.0 to ≤ 7.5% [lenient]).Results8568 patients with T2DM and hypertension were enrolled. 6691 (78.1%) had 12-month follow-up. Patients who were assigned a strict HbA1c treatment target (n = 2644) were younger, had shorter diabetes duration, and less comorbidity in comparison to those with intermediate (n = 2912) or lenient targets (n = 1135). Only 53.1% of patients achieved their HbA1c treatment target (46.2% [strict], 56.8% [intermediate], 59.4% [lenient]). There was little sign of treatment intensification for patients that had not achieved their HbA1c target.ConclusionsAchievement of treatment targets was poor, leaving many patients with sub-optimal blood glucose levels. The apparent reluctance of physicians to intensify antidiabetic drug therapy is alarming, especially considering the evidence pointing to an association of hyperglycaemia and microvascular complications in patients with T2DM.

Efficacy of restarting anti-tumor necrosis factor α agents after surgery in patients with Crohn's disease

Background/AimsThe efficacy of anti-tumor necrosis factor α (anti-TNFα) antibodies for postoperative Crohn's disease (CD) in patients who were treated with these agents prior to surgery is largely unknown.MethodsCD patients who underwent intestinal resection and received anti-TNFα agents after surgery were divided into 2 groups according to the presence or absence of preoperative anti-TNFα treatment: anti-TNFα restart group or anti-TNFα naïve group. Endoscopic recurrence after surgery was examined according to the preoperative conditions, including administration of anti-TNFα agents before surgery.ResultsThirty-six patients received anti-TNFα antibody after surgery: 22 in the anti-TNFα restart group and 14 in the anti-TNFα naïve group. Endoscopic recurrence after surgery was more frequently observed in the anti-TNFα restart group than in the anti-TNFα naïve group (68% vs. 14%, P<0.001). Multivariate analysis revealed the following significant risk factors of endoscopic recurrence after surgery: anti-TNF restart group (odds ratio [OR], 28.10; 95% CI, 3.08–722.00), age at diagnosis <23 years (OR, 24.30; 95% CI, 1.67–1,312.00), serum albumin concentration at surgery <3.3 g/dL (OR, 34.10; 95% CI, 1.72–2,804.00), and presence of inflammation outside of the surgical site (OR, 21.40; 95% CI, 1.02–2,150.00). Treatment intensification for patients with endoscopic recurrence in the anti-TNFα restart group showed limited responses, with only 1 of 12 patients achieving endoscopic remission.ConclusionsThe efficacy of restarting anti-TNFα antibody treatment after surgery was limited, and treatment intensification or a change to different classes of biologics should be considered for those patients.

Anti-infliximab antibody concentrations can guide treatment intensification in patients with Crohn's disease who lose clinical response.

The presence of antibodies towards infliximab (ATI) is associated with lower infliximab (IFX) trough concentrations and loss of response. IFX treatment intensification is effective for restoring response in most, but not all patients with Crohn's disease (CD). To compare outcome, pharmacokinetics and immunogenicity of treatment intensification strategies in patients with CD who lost clinical response to IFX. A retrospective cohort study was conducted, including 103 patients with CD who lost clinical response during IFX maintenance therapy and therefore received a double dose IFX (10 mg/kg) and/or a next infusion after a shortened interval. IFX and ATI concentrations were measured in consecutive trough samples, just before (T0) and after (T+1) treatment intensification. Clinical response (physicians' global assessment) and biological response and remission (CRP) were restored in 63%, 42% and 24% of patients (evaluated at T+1). Treatment intensification increased IFX trough concentrations from 1.2 μg/mL [0.3-3.6] at T0 to 3.6 μg/mL [0.5-10.2] at T+1 (P < .0001). Using a drug tolerant assay, ATI were detected in the T0 sample of 47% of patients. ATI negatively impacted the achieved IFX trough concentration (Spearman r -0.57, P < .0001) and the probability of clinical response (P = 0.034) at T+1. When ATI were quantifiable but <282 ng/mL eq. at T0, combined interval shortening and dose doubling was more effective for restoring therapeutic IFX trough concentrations (≥3 μg/mL at T+1) than dose doubling alone, which in turn was more effective than interval shortening alone (P < .001). Antibodies towards infliximab can guide clinical decision-making on treatment intensification.

Clinical Inertia in Type 2 Diabetes Mellitus: Time in Poor Glycaemic Control Until Treatment Intensification in Patients on DPP-4I And/Or SGLT-2I Treatment

Clinical Inertia in Type 2 Diabetes Mellitus: Time in Poor Glycaemic Control Until Treatment Intensification in Patients on DPP-4I And/Or SGLT-2I Treatment

Hypertension treatment practices and its determinants among ambulatory patients: retrospective cohort study in Ethiopia

ObjectivesWe examined determinants of achieving blood pressure control in patients with hypertension and of treatment intensification in patients with uncontrolled blood pressure (BP).DesignA retrospective cohort study in six public hospitals,...

Therapeutic inertia in patients treated with two or more antidiabetics in primary care: Factors predicting intensification of treatment.

To determine the patterns and predictors of treatment intensification in patients with type 2 diabetes on ≥2 non-insulin antidiabetic drugs (NIADs) and inadequate glycaemic control in primary care in Catalonia, Spain. This was a retrospective analysis using electronic medical records from patients with HbA1c ≥ 7% and a first prescription for a new NIAD or insulin recorded from January 2010 to December 2014. Therapeutic inertia was defined as no intensification if HbA1c was ≥8% at baseline or during follow-up. Time to first intensification was evaluated by time-to-event analysis, and factors predicting intensification through a competing-risk regression model. Among 23 678 patients with HbA1c ≥ 7%, 26.2% were censored without treatment intensification after a median follow up of 4.2 years. Among the 12 730 patients in the subgroup with HbA1c ≥ 8% at baseline or during follow-up, therapeutic inertia was present in 18.1% of cases. In the overall cohort, mean HbA1c at initiation of insulin and NIAD were 9.4% ± 1.5% and 8.7% ± 1.3%, respectively. Median time to first intensification was 17.1 months in patients with HbA1c 8.0% to 9.9%, and 10.1 months in those with HbA1c > 10%. Variables strongly associated with intensification were HbA1c values 8.0% to 9.9% (subhazard ratio [SHR], 1.7; 95% CI, 1.65-1.78) and >10% (SHR, 2.5; 95% CI, 2.37-2.68); diabetes duration ≥20 years (SHR, 1.25; 95% CI, 1.11-1.41) and, to a lesser extent, female gender, presence of comorbidities, chronic kidney disease and microvascular complications. Intensification was not undertaken in 1 in 5 patients. Both HbA1c thresholds and time until therapy intensification exceeded current recommendations.

Value-Based Payments and Incentives to Improve Care: A Case Study of Patients with Type 2 Diabetes in Medicare Advantage.

To estimate the impact of increased glycated hemoglobin (A1C) monitoring and treatment intensification for patients with type 2 diabetes (T2D) on quality measures and reimbursement within the Medicare Advantage Star (MA Star) program. The primary endpoint was the share of patients with T2D with adequate A1C control (A1C ≤ 9%). We conducted a simulation of how increased A1C monitoring and treatment intensification affected this end point using data from the National Health and Nutrition Examination Survey and clinical trials. Using the estimated changes in measured A1C levels, we calculated corresponding changes in the plan-level A1C quality measure, overall star rating, and reimbursement. At baseline, 24.4% of patients with T2D in the average plan had poor A1C control. The share of plans receiving the highest A1C rating increased from 27% at baseline to 49.5% (increased monitoring), 36.2% (intensification), and 57.1% (joint implementation of both interventions). However, overall star ratings increased for only 3.6%, 1.3%, and 4.8% of plans, respectively, by intervention. Projected per-member per-year rebate increases under the MA Star program were $7.71 (monitoring), $2.66 (intensification), and $10.55 (joint implementation). The simulation showed that increased monitoring and treatment intensification would improve A1C levels; however, the resulting average increases in reimbursement would be small.

Cladribine, Cytarabine and Mitoxantrone As Treatment Intensification for Patients with Acute Myeloid Leukemia with the Excess of Bone Marrow Blasts on Day 14 of the First Induction. Prospective, Multicenter Study By the Polish Adult Leukemia Group (PALG)

ObjectivesThe treatment results of acute myeloid leukemia (AML) patients (pts) younger than 60yo are still unsatisfactory. The strategy of double induction in AMLis based on two courses of chemotherapy depends on percentage of bone marrow (BM) blast at 7-14 days of treatment. This therapy intensification may induce higher response rate but toxicity appeared as early death (ED) rates still a medical dilemma. The advantage from addition of cladribine (2CdA) to standard induction and reinduction treatment was previously confirmed in PALG's trials.AimThe aim of this study was an estimation of efficacy and toxicity of treatment intensification based on BM blast at 14 day (D14) by second early induction, CLAM (2CdA + cytarabine + mitoxantron)MethodsWe performed multicenter, prospective, non-randomized trial where pts received DAC induction treatment with subsequent second early induction according as D14 BM biopsy results. When BM examination revealed >10% of blast without hypocellular marrowand pts met all criteria to intensive chemotherapy, second intensive induction with CLAM protocol (2CdA 5mg/m2 iv days 1-5, Cytarabine 2g/m2 iv days 1-5, Mitoxantron 10mg/m2 iv days 1-3) from day 16 was applied. The pts were allocated to risk-adjusted postremission treatment with high-dose cytarabine (HD-AraC) for low-risk group according to European Leukemia Net (ELN) classification and allogeneic stem cell transplantation (allo-SCT) recommended for intermediate and high-risk group.ResultsOne hundred seventy one newly diagnosed AML pts from 8 PALG's centers were enrolled to the study. The median age was 47 yo (range19-60). According to WHO 2008 classification, our group consisted of 9% AML with recurrent genetic abnormalities, 19% AML related to myelodysplasia, 3% therapy-related AML and 69% AML not otherwise classified. Analysis of cytogenetic-molecular risk factors based on ELN classification revealed favorable, intermediate-1, intermediate-2, poor-risk groups in 17%, 44%, 18% and 21% AML pts, respectively. Twenty-six (15%) out of 171 pts had elevated BM infiltration of blasts at D14, with the median 44% (range 11-100%). Overall, 22 of 26 pts were judged as eligible to receive second induction, reasons for exclusion being in all cases active infection.Response evaluation was available in 150 pts, 21 pts were still ongoing in the protocol. Complete remission (CR) rate after single DAC induction course was 71% (n=106), partial remission (PR), non-remission (NR) and ED was 8% (n=12), 18% (n=28) and 3% (n=4), respectively. Response after double induction was evaluated in 21 out of 22 cases; one patient still has not reached time of measurement. CR was observed in 14/21 pts (67%), NR in 5% (n=1), ED 28% (n=6). The CR rate after inductiontreatment applied to first hospitalization (DAC or DAC+ CLAM) was 81% (n=120). Twelve pts who had <10% of blasts at day 14 and achieved PR after first induction were allocated to second DAC induction. Six out of them achieved CR leading to the overall CR rate 85%.In 27 pts who achieved CR allo-SCT was performed till June 2016, however there are pts who are still awaiting allo-SCT.The median duration of hospital stay was 31 (11-73) and 66 (52-76) days respectively for the DAC and the DAC + CLAM induction. During the single DAC induction the median number of days with neutropenia <0.5 G/l was 24 (12-101), and with thrombocytopenia <20 G/l was 12 (0-51). The median number of transfused packed red blood cell (PRBC) was 9 (0-32) and the number of platelet concentrate units was 15 (2-124). During DAC+CLAM double induction the median number of days of the neutropenia <0.5 G/l was 53 (17-73) and thrombocytopenia <20 G/l was 19 (4-57). The median number of PRBC was 18 (10-44) and the number of platelet concentrate units was 30 (5-153).With the median time of follow-up 16 months the median overall survival (OS) was not reached. The probability of 1-year OS was 59% and the probability of 1-year disease free survival was 83% (Figure 1, Panel A and B).ConclusionThe preliminary results of our study suggest that early second induction CLAM is a feasible and effective treatment option in younger AML patients which further improves the CR rate and do not compromise the feasibility of allo-SCT. [Display omitted] DisclosuresGrzybowska-Izydorczyk:BMS: Honoraria; Novartis: Honoraria. Warzocha:BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Robak:Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Wierzbowska:Novartis: Consultancy, Honoraria; Janssen Cilag: Consultancy.

Titration of basal insulin or immediate addition of rapid acting insulin in patients not at target using basal insulin supported oral antidiabetic treatment – A prospective observational study in 2202 patients

AimOptimal treatment intensification strategies in patients with type-2 diabetes mellitus (T2DM) receiving basal insulin supported oral antidiabetic therapy (BOT) remain controversial. The objective of the present study was to compare outcomes of BOT-intensification by either the uptitration of long-acting insulin glargine or by the immediate addition of a rapid acting insulin analogue (RAIA). MethodsThis was a prospective, observational, 24-week study in T2DM patients with BOT using insulin glargine and baseline glycated hemoglobin (HbA1c) between 7.0 and 8.5%. Patients were stratified by their physicians to one of the following treatment intensification strategies: Basal insulin titration to target with discretionary subsequent addition of RAIA at weeks 12 or 24 (GLAR), or immediate addition of RAIA at baseline (GLARplus). ResultsA total of 3266 patients were prescreened of whom 2202 fulfilled the selection criteria. Of these, 1684 patients were documented in the GLAR group and 518 in the GLARplus group. In the GLAR group, in 91 (5.5%) and 21 patients (1.3%) RAIA was added at weeks 12 and 24, respectively. The groups displayed similar baseline characteristics; except, mean diabetes duration was slightly shorter in the GLAR group (8.7 vs. 9.4 years). During the study, insulin glargine dose was increased from 18.7 to 26.4U (plus 7.7U) in GLAR and from 24.9 to 27.3U (plus 2.4U) in GLARplus patients. Mean RAIA dose was 9.6±4.7U at the final visit. After 24 weeks, HbA1c was reduced by 0.8 and 0.9% in the GLAR and GLARplus groups, respectively (both p<0.001). An HbA1c of ≤7.0% was achieved in 49.2% of GLAR and 48.5% of GLARplus patients. In both groups, we observed improvements in cardiovascular risk factors such as lipids and blood pressure. The rates of symptomatic (1.6 vs. 1.7%) and severe (0.18 vs. 0.19%) hypoglycemic episodes were low and comparable in both groups. ConclusionThese findings provide evidence that treatment intensification in patients with type 2 diabetes not at glycemic target on BOT with insulin glargine is equally safe and effective using either long-acting insulin titration alone or the addition of a rapid-acting insulin analogue.

Treatment intensification for patients with type 2 diabetes and poor glycaemic control.

To identify the time to and patient characteristics associated with treatment intensification in patients with type 2 diabetes (T2D) and poor glycaemic control. Using a large US insurance claims database, we conducted a retrospective cohort study among adult patients with T2D and glycated haemoglobin (HbA1c) ≥8% (index date) after ≥3 months of therapy including metformin. Patients were required to have continuous enrolment for at least 12 months before (baseline) and after index date, and no injectable antidiabetes medications. We defined treatment intensification as prescription fill for injectable or additional oral antidiabetic drugs (OADs). Cox modelling was performed to identify factors associated with time to treatment intensification. For the 11 525 patients meeting the inclusion criteria, the mean age at index date was 57 years, 40% were female and the mean index HbA1c was 9.1%. Overall, 37% of patients had their treatment intensified <6 months after, 11% had their treatment intensified 6-12 months after, and 52% did not have their treatment intensified <12 months after the index date. A higher index HbA1c was associated with early intensification [hazard ratio (HR) 1.18 for HbA1c ≥9 to <10% and HR 1.41 for HbA1c ≥10% compared with HbA1c ≥8 to <9%; p < 0.0001), and later line of therapy was associated with late intensification (HR 0.78 for metformin with one OAD and HR 0.68 for metformin with ≥2 OADs compared with metformin monotherapy; p < 0.0001). Fewer than half of patients with T2D and treatment failure received intensification within 12 months in a real-world US population. Factors associated with treatment inertia can be used to target clinical care for these patients.

Treatment intensification in patients with inadequate glycemic control on basal insulin: rationale and clinical evidence for the use of short-acting and other glucagon-like peptide-1 receptor agonists.

SummaryA substantial proportion of patients with type 2 diabetes mellitus do not reach glycemic targets, despite treatment with oral anti‐diabetic drugs and basal insulin therapy. Several options exist for treatment intensification beyond basal insulin, and the treatment paradigm is complex. In this review, the options for treatment intensification will be explored, focusing on drug classes that act via the incretin system and paying particular attention to the short‐acting glucagon‐like peptide‐1 receptor agonists exenatide and lixisenatide. Current treatment guidelines will be summarized and discussed. © 2016 The Authors. Diabetes/Metabolism Research and Reviews Published by John Wiley & Sons Ltd.

Abstract TP175: Intensification of Statin Treatment is Associated With Improved Mortality Among Patients With TIA and Ischemic Stroke

Introduction: Current guidelines for hyperlipidemia among patients with cerebrovascular disease recommend prescribing moderate/high potency statins rather than intensifying (low/moderate) treatment, but whether this treatment approach confers mortality benefits is unclear. Hypothesis: Intensification of statin therapy will be associated with improved outcomes within a given potency strata. Methods: Administrative data were analyzed from a sample of 11,306 Veterans admitted to 134 Veterans Health Administration (VHA) facilities with a TIA or ischemic stroke in fiscal year 2011. Patients who: were transferred to another non-VHA acute care facility or hospice, died in the emergency room/hospital, left against medical advice, had a documented statin allergy were excluded (n=1538). Treatment intensification was defined as an increase in potency class within 7-days of discharge. Multivariable logistic regression models were used to determine whether treatment intensification (vs. none) was associated with differences in 30-day and 1-year mortality. Results: Among 9,768 eligible patients, 66.5 % (n=6494) were prescribed statins at discharge; a majority (90.4%) were prescribed moderate/high potency statins. Treatment intensification occurred among 51.7% and 57.1% of patients in the moderate/high potency and low potency strata, respectively. Compared with patients receiving moderate/high potency statins without intensification, intensification was associated with lower 1-year (odds ratio [OR]=0.51; confidence Interval [CI] 95 :0.33, 0.80) but not 30-day (OR=2.10; CI 95 :0.66, 6.68) mortality. Compared with patients receiving low potency statins without intensification, intensification was associated with lower 1-year (OR=0.79 CI 95 :0.67, 0.93) and thirty-day (OR=0.72; CI 95 :0.52, 0.99) mortality. Conclusion: Treatment intensification for patients receiving moderate/high or low potency statins was associated with improved mortality after a cerebrovascular event, with potential implications for future treatment guidelines.

Glycemic excursions are positively associated with changes in duration of asymptomatic hypoglycemia after treatment intensification in patients with type 2 diabetes

AimThe aim of this study was to examine the association between glycemic excursions and duration of hypoglycemia after treatment intensification in patients with type 2 diabetes (T2D). MethodsPatients with T2D on oral anti-diabetes drug (OAD) with glycated hemoglobin (HbA1c) of 7.0–11.0% were switched to metformin monotherapy (500mg thrice daily) for 8 weeks, followed by randomization to either glibenclamide or acarbose as add-on treatment for 16 weeks. Glycemic excursions were assessed as mean amplitude of glycemic excursions (MAGE) with 72-h ambulatory continuous glucose monitoring (CGM) before randomization and at the end of study. Hypoglycemia was defined as sensor glucose level of less than 60mg/dl in two or more consecutive readings from CGM. ResultsA total of 50 patients (mean age 53.5±8.2 years, male 48%, mean baseline HbA1c 8.4±1.2%) were analyzed. Duration of hypoglycemia significantly increased after treatment with glibenclamide (from 5.5±13.8 to 18.8±35.8min/day, p=0.041), but not with acarbose (from 2.9±10.9 to 14.7±41.9min/day, p=0.114). Post treatment MAGE was positively associated with change from baseline in duration of hypoglycemia after treatment with either glibenclamide (β coefficient 0.345, p=0.036) or acarbose (β coefficient 0.674, p=0.046). The association remained significant after multivariate adjustment (p<0.05 for all models). ConclusionsPost treatment glycemic excursions are associated with changes in duration of hypoglycemia after treatment intensification with OAD in patients with T2D. Glycemic excursions should be an important treatment target for T2D to reduce the risk of hypoglycemia.

Early Treatment Intensification with R-ICE Chemotherapy Followed By Autologous Stem Cell Transplantation (ASCT) Using Zevalin-BEAM for Patients with Poor Risk Diffuse Large B-Cell Lymphoma (DLBCL) As Identified By Interim PET/CT Scan Performed after Four Cycles of R-CHOP-14: A Multicenter Phase II Study of the Australasian Leukaemia Lymphoma Study Group (ALLG)

Early Treatment Intensification with R-ICE Chemotherapy Followed By Autologous Stem Cell Transplantation (ASCT) Using Zevalin-BEAM for Patients with Poor Risk Diffuse Large B-Cell Lymphoma (DLBCL) As Identified By Interim PET/CT Scan Performed after Four Cycles of R-CHOP-14: A Multicenter Phase II Study of the Australasian Leukaemia Lymphoma Study Group (ALLG)

Active interventions in hypercholesteroloemia patients with high cardiovascular risk in primary care; estudio ESPROCOL

Hypercholesterolemia is a major modifiable risk factors for cardiovascular disease (CVD). Its reduction reduces morbidity and mortality from ischemic heart disease and CVD in general, primary prevention and secondary prevention especially. To determine whether a notarized and intensive clinical practice can overcome inertia and achieve the therapeutic goal (OT) LDL-C <100 mg/dL in high-risk patients attended in Primary Care (PC) in our country. Epidemiological, prospective, multicenter study conducted in centers of different ACs By AP consecutive sampling 310 patients at high cardiovascular risk (diabetic or established CVD) previously treated with statins, which did not reach the OT included c-LDL. The study subjects had a mean age of 65.2 years, of which 60.32% were male. The 41.64% had a previous EVC, acute myocardial infarction (20.33%), angina (16.07%), stroke/TIA (9.19%), arthropathy (5.25%), diabetes (70.87%), hypertension (71.01%), and abdominal obesity (69.62%). The 43.57% (95% CI: 37,21; 50,08) of patients who performed the 2nd visit (241) got the OT. 62.50% (95% CI: 55.68, 68.98) of those who took the 3rd (216) got the OT. Finally, 77.56% (95% CI: 72.13, 83.08) patients who performed the last visit (205) got the OT. Throughout the study there was a reduction in LDL-C levels from 135.6 mg/dL at baseline, 107.4 mg dL in the 2nd visit, 97.3 mg/dL in the 3rd visit, up to 90.7 mg/dL at the final visit (p < 0.0001). The increase in HDL-C from baseline (50.9 mg/dL) and final (53.6 mg/dL) was also significant (p = 0.013). The reassessment and intensification of treatment in patients at high cardiovascular risk treated in primary care, applying the indications of the guides, achieves the OT in more than three quarters of the previously uncontrolled within half a year. These results should encourage us to overcome the therapeutic inertia in the control of CVD by early and energetic performance against hypercholesterolemia.