Expert Panel Recommendations for a Standardized Ambulatory Glucose Profile Report for Connected Insulin Pens.

Background: Connected insulin pens capture data on insulin dosing/timing and can integrate with continuous glucose monitoring (CGM) devices with essential insulin and glucose metrics combined into a single platform. Standardization of connected insulin pen reports is desirable to enhance clinical utility with a single report. Methods: An international expert panel was convened to develop a standardized connected insulin pen report incorporating insulin and glucose metrics into a single report containing clinically useful information. An extensive literature review and identification of examples of current connected insulin pen reports were performed serving as the basis for creation of a draft of a standardized connected insulin pen report. The expert panel participated in three virtual standardization meetings and online surveys. Results: The Ambulatory Glucose Profile (AGP) Report: Connected Insulin Pen brings all clinically relevant CGM-derived glucose and connected insulin pen metrics into a single simplified two-page report. The first page contains the time in ranges bar, summary of key insulin and glucose metrics, the AGP curve, and detailed basal (long-acting) insulin assessment. The second page contains the bolus (mealtime and correction) insulin assessment periods with information on meal timing, insulin-to-carbohydrate ratio, average bolus insulin dose, and number of days with bolus doses recorded. The report's second page contains daily glucose profiles with an overlay of the timing and amount of basal and bolus insulin administered. Conclusion: The AGP Report: Connected Insulin Pen is a standardized clinically useful report that should be considered by companies developing connected pen technology as part of their system reporting/output.

Practical Considerations for Initiating and Utilizing Flash Continuous Glucose Monitoring in Clinical Practice.

Use of continuous glucose monitoring (CGM) has been shown to improve clinical outcomes in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D), including improved glycemic control, better treatment adherence, and an increased understanding of their treatment regimens. Retrospective analysis of CGM data allows clinicians and patients to identify glycemic patterns that support and facilitate informed therapy adjustments. There are currently 2 types of CGM systems: real-time CGM (rtCGM) and flash CGM. The FreeStyle Libre 2 (FSL2) is the newest flash CGM system commercially available. Because the FSL2 system was only recently cleared for use in the US, many endocrinologists and diabetes specialists may be unfamiliar with the strengths, limitations, and potential of the FSL2 system. This article focuses on practical approaches and strategies for initiating and using flash CGM in endocrinology and diabetes specialty practices.

Further improvement in glycemic control after switching from exenatide two times per day to exenatide once-weekly autoinjected suspension in patients with type 2 diabetes: 52-week results from the DURATION-NEO-1 study.

INTRODUCTION: Investigate the effects of switching from two times per day exenatide to once-weekly exenatide administered by autoinjector (exenatide once-weekly suspension by autoinjector (QWS-AI)) or treatment with exenatide QWS-AI for 1 year. RESEARCH DESIGN AND METHODS: In this phase III open-label study, adults with type 2 diabetes were randomized to receive exenatide QWS-AI (2 mg) or exenatide two times per day (5 mcg for 4 weeks, followed by 10 mcg) for 28 weeks. During a subsequent non-randomized 24-week extension, patients who received exenatide two times per day were switched to exenatide QWS-AI and those randomized to exenatide QWS-AI continued this treatment. Efficacy measures included changes from baseline in glycated hemoglobin (A1C), fasting plasma glucose (FPG), and body weight. RESULTS: In total, 315 patients (mean baseline A1C of 8.5%) completed the initial 28 weeks of randomized treatment with exenatide QWS-AI (n=197) or exenatide two times per day (n=118) and were included in the 24-week extension (mean A1C of 7.0% and 7.3%, respectively, at week 28). From weeks 28-52, patients who switched from exenatide two times per day to exenatide QWS-AI had additional A1C reductions of approximately 0.5% (mean A1C change from baseline of -1.4% at week 52) and further reductions from baseline in FPG. Patients who continued exenatide QWS-AI treatment for 52 weeks showed clinically relevant A1C reductions (mean A1C change from baseline of -1.3% at week 52). Body-weight reductions achieved through week 28 were sustained at week 52 in both groups. There were no unexpected safety concerns or changes in the safety profile among patients who switched from exenatide two times per day to exenatide QWS-AI or those who continued exenatide QWS-AI treatment for 52 weeks. CONCLUSIONS: Switching from exenatide two times per day to exenatide QWS-AI resulted in further A1C reductions and maintenance of earlier decreases in body weight, while continued therapy with exenatide QWS-AI for 52 weeks maintained A1C and body-weight reductions, without additional safety or tolerability concerns. TRIAL REGISTRATION NUMBER: NCT01652716.

GLP-1 receptor agonists in the treatment of type 2 diabetes: role and clinical experience to date.

Glucagon-like peptide-1 (GLP-1) is a hormone of the incretin system responsible for a variety of glucoregulatory effects, including glucose-dependent secretion of insulin and inhibition of glucagon release, the effects of which are impaired in people with type 2 diabetes (T2D). Targeting this deficiency using GLP-1 receptor agonists (GLP-1RAs) is a well-established approach in T2D, with over a decade of clinical experience now accrued. This article reviews the evidence for subcutaneous GLP-1RAs and their role in T2D treatment, and explores the rationale for an oral GLP-1RA from a primary care perspective. Clinical trials and real-world studies with subcutaneous GLP-1RAs indicate that these agents have good glycated hemoglobin (HbA1 c)-lowering efficacy, an inherently low potential for hypoglycemia, and reduce body weight. Cardiovascular outcomes trials have established cardiovascular safety, and three GLP-1RAs have been proven to reduce the risk of major adverse cardiovascular events (MACE) in patients with established cardiovascular disease or at high cardiovascular risk. The most common adverse events associated with GLP-1RAs are gastrointestinal effects, which tend to occur soon after initiation and decline over time. T2D treatment guidelines recommend GLP-1RAs as a therapeutic option in various settings, including in those patients: i) not achieving HbA1 c targets after first-line metformin and lifestyle modifications; ii) at high risk of/with established atherosclerotic cardiovascular disease (regardless of HbA1c; GLP-1RAs of proven benefit); iii) not achieving HbA1 c targets on basal insulin if not already receiving a GLP-1RA. Despite the known benefits of GLP-1RAs, adherence and persistence rates are suboptimal, potentially due in part to injection-related concerns. With some patients having a preference for oral medications, the development of an oral GLP-1RA is a logical approach to improving treatment options for patients with T2D. Co-formulation of semaglutide with an absorption enhancer has enabled the development and recent approval of the first oral GLP-1RA, oral semaglutide, which has the potential to expand use of GLP-1RAs in clinical practice.

Development of risk models for major adverse chronic renal outcomes among patients with type 2 diabetes mellitus using insurance claims: a retrospective observational study.

Objective: To develop and validate models allowing the prediction of major adverse chronic renal outcomes (MACRO) in patients with type 2 diabetes mellitus (T2DM) using insurance claims data.Methods: The Optum Integrated Real World Evidence Electronic Health Records and Claims de-identified database (10/01/2006-09/30/2016) was used to identify T2DM patients ≥50 years old. Risk factors were assessed over a 12-month baseline period, and MACRO were subsequently assessed until the end of data availability, continuous enrollment, or death. Separate models were built for moderate-to-severe diabetic kidney disease (DKD), end-stage renal disease (ESRD), and renal death. A random split-sample approach was employed, where 70% of the sample served for model development (training set) and the remaining 30% served for validation (testing set). C-statistics were used to assess model performance.Results: A total of 160,031 patients were included. Risk factors associated with MACRO for all models included adapted diabetes complications severity index, heart failure, anemia, diabetic nephropathy, and CKD. C-statistics ranged between 0.70 (moderate-to-severe DKD) and 0.84 (renal death) in the testing set. A substantial proportion (e.g. 88.7% for moderate-to-severe DKD) of patients predicted to be at high-risk of MACRO did not have diabetic nephropathy, proteinuria, or CKD at baseline.Conclusions: The models developed using insurance claims data could reliably predict the risk of MACRO in patients with T2DM and enabled patients at higher-risk of DKD to be identified in the absence of baseline diabetic nephropathy, CKD, or proteinuria. These models could help establish strategies to reduce the risk of MACRO in T2DM patients.

Practical Guidance on Effective Basal Insulin Titration for Primary Care Providers.

IN BRIEF Basal insulin therapy is well established for glycemic control in patients with diabetes but often is not optimally implemented, leading to poor clinical outcomes and adherence. Primary care providers can and should work together with other members of the diabetes care team to allow for effective titration of basal insulin that involves patients and their caregivers. Adequate guidance and monitoring during the titration process can minimize some of the adverse effects caused by basal insulin administration, while improving glycemic control in a timely manner.

Effect of Insulin Degludec Versus Insulin Glargine U100 on Hypoglycemia in Hispanic Patients With Type 2 Diabetes: Results From the SWITCH 2 Trial.

IN BRIEF Hispanic patients with type 2 diabetes have poorer glycemic control and are at higher risk of severe diabetes complications and mortality than non-Hispanic white patients. This post hoc analysis investigated the safety and efficacy of insulin degludec versus insulin glargine 100 units/mL (glargine U100) in the Hispanic patient subpopulation from the SWITCH 2 trial. In Hispanic patients, hypoglycemia was consistently lower and nocturnal hypoglycemia was significantly lower with degludec versus glargine U100 at similar levels of glycemic control. Overall, results in Hispanic patients in SWITCH 2 were consistent with those in non-Hispanic patients.

Efficacy and tolerability of exenatide once weekly over 7 years in patients with type 2 diabetes: An open-label extension of the DURATION-1 study.

AIMS: To investigate the glycemic efficacy, effects on cardiovascular risk factors, and safety of exenatide once weekly (QW) in patients with type 2 diabetes over 7 years in the DURATION-1 study. METHODS: Patients were initially randomized to exenatide QW 2 mg or exenatide twice daily for 30 weeks, after which they received open-label, open-ended treatment with exenatide QW 2 mg for up to 7 years. Efficacy analyses included changes from baseline in glycated hemoglobin (HbA1C) and cardiovascular risk factors. RESULTS: Of 295 patients in the intention-to-treat population, 122 (41%) completed 7 years of treatment. Patients in the 7-year completer population showed sustained glycemic improvements from baseline (7-year least-squares mean [LSM] change in HbA1C, -1.53%) and significant improvements in several cardiovascular risk factors, including body weight, diastolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Seven-year completers who received no additional glucose-lowering therapies (n = 65 [53%]) had similar improvements in HbA1C, and numerically greater reductions in body weight (7-year LSM change, -6.46 kg vs -3.87 kg), compared with the overall cohort. There were no unexpected safety findings. CONCLUSIONS: Treatment with exenatide QW for 7 years was associated with sustained improvements in glycemic control and several cardiovascular risk factors.

Evaluation of the Use of Exenatide Once-Weekly Suspension Autoinjector Among Patients With Type 2 Diabetes Mellitus and Health Care Professionals.

BACKGROUND: Ease of injection is important to patients. An autoinjector was developed to deliver exenatide, a glucagon-like peptide-1 receptor agonist for type 2 diabetes mellitus. For autoinjection, 0.06-mm exenatide-containing microspheres are suspended in medium-chain triglycerides. Herein, we report design verification and usability testing of the autoinjector for exenatide once-weekly suspension (QWS) delivery. METHODS: Exenatide QWS in a single-chamber cartridge is self-injected subcutaneously with three main steps: mix, unlock, and inject. Design verification testing used validated testing methodology. A summative validation study with simulated-use scenarios evaluated unassisted performance on critical tasks (ease of use and the injection process). RESULTS: The autoinjector met specified design requirements for dose accuracy and torque/force. Of 104 participants enrolled (73 lay users, 16 health care professionals, and 15 pharmacists), 90 independently referred to instructions for use during testing. Users successfully achieved critical tasks on first attempt 87-100% of the time. Approximately 78% of participants successfully completed the full injection scenario, including 72% of lay users reporting visual or dexterity impairments. Initial use errors on critical tasks included not mixing well (n = 12), not removing needle cap (n = 8), and not holding needle to the skin for complete injection (n = 5). Untrained injection-naïve and trained injection-experienced lay users made the fewest errors (7% and 3%, respectively). Trained and untrained participants took 2:33 and 5:03 minutes, respectively, to complete a weekly injection. CONCLUSIONS: Users with a range of injection experience can rapidly learn to administer exenatide QWS autoinjector correctly, thus minimizing patient effort to manage their diabetes with injectable therapy.

Day-to-day fasting self-monitored blood glucose variability is associated with risk of hypoglycaemia in insulin-treated patients with type 1 and type 2 diabetes: A post hoc analysis of the SWITCH Trials.

AIMS: To investigate the association between day-to-day fasting self-monitored blood glucose (SMBG) variability and risk of hypoglycaemia in type 1 (T1D) and type 2 diabetes (T2D), and to compare day-to-day fasting SMBG variability between treatments with insulin degludec (degludec) and insulin glargine 100 units/mL (glargine U100). MATERIALS AND METHODS: Data were retrieved from two double-blind, randomized, treat-to-target, two-period (32 weeks each) crossover trials of degludec vs glargine U100 in T1D (SWITCH 1, n = 501) and T2D (SWITCH 2, n = 720). Available fasting SMBGs were used to determine the standard deviation (SD) of day-to-day fasting SMBG variability for each patient and the treatment combination. The association between day-to-day fasting SMBG variability and overall symptomatic, nocturnal symptomatic and severe hypoglycaemia was analysed for the pooled population using linear regression, with fasting SMBG variability included as a three-level factor defined by population tertiles. Finally, day-to-day fasting SMBG variability was compared between treatments. RESULTS: Linear regression showed that day-to-day fasting SMBG variability was significantly associated with overall symptomatic, nocturnal symptomatic and severe hypoglycaemia risk in T1D and T2D (P < 0.05). Day-to-day fasting SMBG variability was significantly associated (P < 0.01) with all categories of hypoglycaemia risk, with the exception of severe hypoglycaemia in T2D when analysed within tertiles. Degludec was associated with 4% lower day-to-day fasting SMBG variability than glargine U100 in T1D (P = 0.0082) and with 10% lower day-to-day fasting SMBG variability in T2D (P < 0.0001). CONCLUSIONS: Higher day-to-day fasting SMBG variability is associated with an increased risk of overall symptomatic, nocturnal symptomatic and severe hypoglycaemia. Degludec has significantly lower day-to-day fasting SMBG variability vs glargine U100.

An investigation into the durability of glycemic control in patients with type II diabetes initiated on canagliflozin or sitagliptin: A real-world analysis of electronic medical records.

AIMS: The aims of this study were to assess glycemic control, weight loss, and durability of glycemic control in patients initiated on canagliflozin (CANA) versus sitagliptin (SITA). METHODS: Adults with type II diabetes mellitus initiated on CANA or SITA (index date) were identified from IQVIA™ Real-World Data Electronic Medical Records - US database (03/29/2012-04/30/2016). Inverse probability of treatment weighting accounted for baseline differences between cohorts. Outcomes were compared using weighted Cox regression and Kaplan-Meier curves and included time to reaching HbA1c thresholds (<7%[53 mmol/mol], <8%[64 mmol/mol], <9%[75 mmol/mol]), weight loss ≥5%, failure to maintain HbA1c below threshold, new antihyperglycemic (AHA) prescription, and failure to maintain HbA1c/new AHA prescription. RESULTS: Weighted cohorts were well balanced (NCANA = 14,542; NSITA = 15,151). CANA patients were 12-15% more likely to reach the HbA1c thresholds, 47% more likely to lose ≥5% of body weight, 31% less likely to have a new AHA prescription, 10-15% less likely to fail to maintain HbA1c, and 13-26% less likely to fail to maintain HbA1c or have a new AHA, versus SITA patients. CONCLUSIONS: CANA patients were more likely to reach HbA1c and weight loss thresholds and maintain HbA1c below threshold versus SITA patients, while being less likely to have a prescription for a new AHA, suggesting more durable glycemic control with CANA.

Development of predictive risk models for major adverse cardiovascular events among patients with type 2 diabetes mellitus using health insurance claims data.

BACKGROUND: There exist several predictive risk models for cardiovascular disease (CVD), including some developed specifically for patients with type 2 diabetes mellitus (T2DM). However, the models developed for a diabetic population are based on information derived from medical records or laboratory results, which are not typically available to entities like payers or quality of care organizations. The objective of this study is to develop and validate models predicting the risk of cardiovascular events in patients with T2DM based on medical insurance claims data. METHODS: Patients with T2DM aged 50 years or older were identified from the Optum™ Integrated Real World Evidence Electronic Health Records and Claims de-identified database (10/01/2006-09/30/2016). Risk factors were assessed over a 12-month baseline period and cardiovascular events were monitored from the end of the baseline period until end of data availability, continuous enrollment, or death. Risk models were developed using logistic regressions separately for patients with and without prior CVD, and for each outcome: (1) major adverse cardiovascular events (MACE; i.e., non-fatal myocardial infarction, non-fatal stroke, CVD-related death); (2) any MACE, hospitalization for unstable angina, or hospitalization for congestive heart failure; (3) CVD-related death. Models were developed and validated on 70% and 30% of the sample, respectively. Model performance was assessed using C-statistics. RESULTS: A total of 181,619 patients were identified, including 136,544 (75.2%) without prior CVD and 45,075 (24.8%) with a history of CVD. Age, diabetes-related hospitalizations, prior CVD diagnoses and chronic pulmonary disease were the most important predictors across all models. C-statistics ranged from 0.70 to 0.81, indicating that the models performed well. The additional inclusion of risk factors derived from pharmacy claims (e.g., use of antihypertensive, and use of antihyperglycemic) or from medical records and laboratory measures (e.g., hemoglobin A1c, urine albumin to creatinine ratio) only marginally improved the performance of the models. CONCLUSION: The claims-based models developed could reliably predict the risk of cardiovascular events in T2DM patients, without requiring pharmacy claims or laboratory measures. These models could be relevant for providers and payers and help implement approaches to prevent cardiovascular events in high-risk diabetic patients.

Safety and Efficacy of Insulin Degludec/Liraglutide (IDegLira) and Insulin Glargine U100/Lixisenatide (iGlarLixi), Two Novel Co-Formulations of a Basal Insulin and a Glucagon-Like Peptide-1 Receptor Agonist, in Patients With Diabetes Not Adequately Controlled on Oral Antidiabetic Medications.

IN BRIEF Novel co-formulations of basal insulin analogs and glucagon-like peptide-1 (GLP-1) receptor agonists have provided new options for patients with type 2 diabetes who are not reaching recommended glycemic targets. The components of currently available co-formulations (insulin degludec/ liraglutide [IDegLira,] and insulin glargine U100/lixisenatide [iGlarLixi]) act synergistically to address multiple pathophysiologic defects while minimizing the side effects associated with either component when used alone. In Europe, these products are approved for use in patients on regimens of one or more oral antidiabetic drugs; in the United States, they are indicated for use as an adjunct to diet and exercise in patients with type 2 diabetes inadequately controlled with either basal insulin or their respective GLP-1 receptor agonist component. This article reviews key clinical trials in which these products were initiated in insulin-naive patients and describes how they can be safely and effectively titrated in clinical practice.

Quality goal attainment and maintenance in patients with type II diabetes mellitus initiated on canagliflozin or a glucagon-like peptide-1 receptor agonist in an actual practice setting.

OBJECTIVE: To compare achievement of quality goals (HbA1c, weight loss/body mass index [BMI], systolic blood pressure [SBP]), including maintaining HbA1c, between patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin 300 mg (CANA) or a GLP-1 in an actual practice setting. METHODS: Adults with T2DM newly initiated on CANA or a GLP-1 were identified from the IQVIATM Real-World Data Electronic Medical Records-US database (2012Q2-2016Q1). To account for differences in baseline characteristics, inverse probability of treatment weighting was used. Outcomes were compared using Cox models (hazard ratios [HRs] and 95% confidence intervals [CIs]) and Kaplan-Meier analyses. RESULTS: CANA (n = 11,435) and GLP-1 (n = 11,582) cohorts had similar attainment of HbA1c < 8.0% (64 mmol/mol) and HbA1c < 9.0% (75 mmol/mol; HbA1c < 8.0%: HR [CI] = 0.98 [0.91-1.06]; HbA1c < 9.0%: HR [CI] = 1.02 [0.93-1.12]), while GLP-1 patients were 10% more likely to achieve HbA1c < 7.0% (53 mmol/mol). CANA and GLP-1 patients were similar in maintaining HbA1c < 7.0%, < 8.0%, or <9.0%, achieving weight loss ≥5% (HR [CI] = 1.05 [0.99-1.12]), achieving BMI <30 kg/m2 (HR [CI] = 1.11 [0.98-1.27]), and achieving SBP <140 mmHg (HR [CI] = 1.07 [0.98-1.17]). CANA patients were 30% less likely to discontinue treatment, 28% less likely to have a prescription for a new anti-hyperglycemic, and 17-21% less likely to fail to maintain HbA1c < 8.0% or 9.0% or have a prescription for a new anti-hyperglycemic (composite outcome) vs GLP-1. No significant difference was observed for the composite outcome using the HbA1c < 7.0% threshold. CONCLUSIONS: This retrospective study in an actual practice setting showed that CANA patients were generally as likely as GLP-1 patients to achieve HbA1c, weight, and blood pressure thresholds, and to maintain glycemic control while being less likely to discontinue treatment and/or have a new anti-hyperglycemic prescribed.

HBA1C CONTROL AND COST-EFFECTIVENESS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS INITIATED ON CANAGLIFLOZIN OR A GLUCAGON-LIKE PEPTIDE 1 RECEPTOR AGONIST IN A REAL-WORLD SETTING.

OBJECTIVE: To compare glycated hemoglobin (HbA1c) control and medication costs between patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin 300 mg (CANA) or a glucagon-like peptide 1 receptor agonist (GLP-1 RA) in a real-world setting. METHODS: Adults with T2DM newly initiated on CANA or a GLP-1 RA (index date) were identified from IQVIA™ Real-World Data Electronic Medical Records U.S. database (March 29, 2012-April 30, 2016). Inverse probability of treatment weighting accounted for differences in baseline characteristics. HbA1c levels at 3-month intervals were compared using generalized estimating equations. Medication costs used wholesale acquisition costs. RESULTS: For both cohorts (CANA: n = 11,435; GLP-1 RA: n = 11,582), HbA1c levels decreased at 3 months postindex and remained lower through 30 months. Absolute changes in mean HbA1c from index to 3 months postindex for CANA and GLP-1 RA were -1.16% and -1.21% (patients with baseline HbA1c ≥7% [53 mmol/mol]); -1.54% and -1.51% (patients with baseline HbA1c ≥8% [64 mmol/mol]); and -2.13% and -1.99% (patients with baseline HbA1c ≥9% [75 mmol/mol]), respectively. Postindex, CANA patients with baseline HbA1c ≥7% had similar HbA1c levels at each interval versus GLP-1 RA patients, except 9 months (mean HbA1c, 7.75% [61 mmol/mol] vs. 7.86% [62 mmol/mol]; P = .0305). CANA patients with baseline HbA1c ≥8% and ≥9% had consistently lower HbA1c numerically versus GLP-1 RA patients and statistically lower HbA1c at 9 (baseline HbA1c ≥8% or ≥9%), 27, and 30 months (baseline HbA1c ≥9%). Continuous 12-month medication cost $3,326 less for CANA versus GLP-1 RA. CONCLUSION: This retrospective study demonstrated a similar evolution of HbA1c levels among CANA and GLP-1 RA patients in a real-world setting. Lower medication costs suggest CANA is economically dominant over GLP-1 RA (similar effectiveness, lower cost). ABBREVIATIONS: AHA = antihyperglycemic agent BMI = body mass index CANA = canagliflozin 300 mg DCSI = diabetes complications severity index eGFR = estimated glomerular filtration rate EMR = electronic medical record GLP-1 RA = glucagon-like peptide 1 receptor agonist HbA1c = glycated hemoglobin ICD-9-CM = International Classification of Diseases-Ninth Revision-Clinical Modification ICD-10-CM = International Classification of Diseases-Tenth Revision-Clinical Modification IPTW = inverse probability of treatment weighting ITT = intent-to-treat MPR = medication possession ratio PDC = proportion of days covered PS = propensity score PSM = propensity score matching Quan-CCI = Quan-Charlson comorbidity index SGLT2 = sodium-glucose cotransporter 2 T2DM = type 2 diabetes mellitus WAC = wholesale acquisition cost.

Efficacy and tolerability of the new autoinjected suspension of exenatide once weekly versus exenatide twice daily in patients with type 2 diabetes.

AIMS: To simplify administration of aqueous exenatide once weekly, which requires reconstitution, the exenatide microspheres have been reformulated in a ready-to-use autoinjector with a Miglyol diluent (exenatide QWS-AI). This study compared the efficacy and safety of exenatide QWS-AI with the first-in-class glucagon-like peptide-1 receptor agonist exenatide twice daily (BID). MATERIALS AND METHODS: This randomized, open-label, controlled study in patients with type 2 diabetes using diet and exercise or taking stable oral glucose-lowering medication randomized patients 3:2 to either exenatide QWS-AI (2 mg) or exenatide BID (10 µg) for 28 weeks. The primary outcome was the 28-week change in glycated haemoglobin (HbA1c). A subset of patients completed a standardized meal test for postprandial and pharmacokinetic assessments. RESULTS: A total of 375 patients (mean HbA1c, 8.5% [69 mmol/mol]; body mass index, 33.2 kg/m2 ; diabetes duration, 8.5 years) received either exenatide QWS-AI (n = 229) or exenatide BID (n = 146); HbA1c was reduced by -1.4% and -1.0%, respectively (least-squares mean difference, -0.37%; P = .0072). More patients achieved HbA1c <7.0% with exenatide QWS-AI (49.3%) than with exenatide BID (43.2%; P = .225). Body weight was reduced in both groups (P = .37 for difference). Gastrointestinal adverse events (AEs) were reported in 22.7% (exenatide QWS-AI) and 35.6% (exenatide BID) of patients; fewer patients in the exenatide QWS-AI group withdrew because of AEs than in the exenatide BID group. Minor hypoglycaemia occurred most often with concomitant sulfonylurea use. CONCLUSIONS: Exenatide QWS-AI was associated with a greater reduction in HbA1c, similar weight loss and a favorable gastrointestinal AE profile compared with exenatide BID.

Glycaemic control and hypoglycaemia in people with type 2 diabetes switching from twice-daily basal insulin to once-daily insulin glargine 300 U/mL or insulin glargine 100 U/mL (EDITION 1 and EDITION 2 subgroup analysis).

In this post hoc analysis we compared glycaemic control and hypoglycaemia between insulin glargine 300 U/mL (Gla-300) and glargine 100 U/mL (Gla-100) administered once daily in people with type 2 diabetes (T2DM) from the EDITION 1 (basal plus mealtime insulin) and EDITION 2 (basal insulin plus oral antihyperglycaemic drugs) trials who were previously receiving twice-daily insulin. At randomization, 16.9% and 20.0% of people in EDITION 1 and 2, respectively, were receiving twice-daily basal insulin. Glycated haemoglobin change from baseline to Month 6 was similar over 6 months with Gla-300 or Gla-100 (least squares mean difference -0.01%; 95% confidence interval [CI] -0.27 to 0.24] in EDITION 1 and 0.16%; 95% CI -0.25 to 0.57, in EDITION 2). Participants previously receiving twice-daily insulin in EDITION 1 had a lower risk of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia with Gla-300 vs Gla-100 at night (00:00-05:59 hours), but not at any time (24 hours); in EDITION 2 the risk was reduced at night and any time (24 hours). In conclusion, Gla-300 provided similar glycaemic control with less hypoglycaemia compared with Gla-100 in people with T2DM switching from twice-daily to once-daily basal insulin.

Quality measure and weight loss assessment in patients with type 2 diabetes mellitus treated with canagliflozin or dipeptidyl peptidase-4 inhibitors.

BACKGROUND: Achieving control of glycated hemoglobin (HbA1c), blood pressure (BP), and body weight (BW) remains a challenge for most patients with type 2 diabetes mellitus (T2DM). In clinical trials, canagliflozin (CANA), an inhibitor of sodium-glucose co-transporter 2, has shown significant improvement compared to some dipeptidyl peptidase-4 (DPP-4) inhibitors in the achievement of such quality measures. This study used recent electronic medical records (EMR) data to assess quality measure achievement of HbA1C, BP, and BW loss in patients treated with CANA versus DPP-4 inhibitors. METHODS: Adult patients with ≥1 T2DM diagnosis and ≥12 months of clinical activity (baseline) before first CANA or DPP-4 prescription (index) were identified in the QuintilesIMS Health Real-World Data EMRs-US database (03/29/2012-10/30/2015). Patients were observed from the index to last encounter. Inverse probability of treatment weighting (IPTW) was used to adjust for observed baseline confounders between groups. Kaplan-Meier (KM) rates and Cox proportional hazard models were used to compare achievement of HbA1c < 7% (among patients <65 years old), HbA1c < 8%, systolic BP < 140 mmHg, diastolic BP < 90 mmHg, and BW loss ≥ 5% among patients not meeting these respective targets at baseline. RESULTS: A total of 10,702 CANA and 17,679 DPP-4 patients were selected. IPTW resulted in balanced baseline demographic, comorbidity, and disease characteristics (CANA: N = 13,793, mean age: 59.0 years; DPP-4: N = 14,588, mean age: 58.9 years). Up until 24 months post-index, CANA patients were more likely to reach an HbA1c < 7% (hazard ratio [HR] = 1.10, P = 0.007, KM rates: 42.8% vs. 40.3%), an HbA1c < 8% (HR = 1.16, P < 0.001, KM rates: 63.7% vs. 60.0%), and a BW loss ≥ 5% (HR = 1.46, P < 0.001, KM rates: 55.2% vs. 46.2%), compared to DPP-4 patients. Up until 12 months post-index, CANA patients were more likely to reach a systolic BP < 140 mmHg (HR = 1.07, P = 0.04, KM rates: 87.8% vs. 83.9%). but not a diastolic BP < 90 mmHg (HR = 0.95, P = 0.361), compared to DPP-4 patients. CONCLUSIONS: This retrospective study of EMR data covering up to 30 months after CANA approval (March 2013) suggests that patients initiated on CANA were more likely to reach HbA1c, systolic BP, and weight loss objectives specified by general diabetes care guidelines than patients initiated on DPP-4 inhibitors.