Engineering digital biomarkers of interstitial glucose from noninvasive smartwatches.

Prediabetes affects one in three people and has a 10% annual conversion rate to type 2 diabetes without lifestyle or medical interventions. Management of glycemic health is essential to prevent progression to type 2 diabetes. However, there is currently no commercially-available and noninvasive method for monitoring glycemic health to aid in self-management of prediabetes. There is a critical need for innovative, practical strategies to improve monitoring and management of glycemic health. In this study, using a dataset of 25,000 simultaneous interstitial glucose and noninvasive wearable smartwatch measurements, we demonstrated the feasibility of using noninvasive and widely accessible methods, including smartwatches and food logs recorded over 10 days, to continuously detect personalized glucose deviations and to predict the exact interstitial glucose value in real time with up to 84% and 87% accuracy, respectively. We also establish methods for designing variables using data-driven and domain-driven methods from noninvasive wearables toward interstitial glucose prediction.

An open trial of app-assisted acceptance and commitment therapy (iACT) for eating disorders in type 1 diabetes.

BACKGROUND: Eating disorders (EDs) among individuals with type 1 diabetes (T1D) increase the risk of early and severe diabetes-related medical complications and premature death. Conventional eating disorder (ED) treatments have been largely ineffective for T1D patients, indicating the need to tailor treatments to this patient population and the unique conditions under which ED symptoms emerge (in the context of a chronic illness with unrelenting demands to control blood glucose, diet and exercise). The current study was a pilot open trial of iACT, a novel intervention for EDs in T1D grounded in Acceptance and Commitment Therapy (ACT). iACT was based on the premise that ED symptoms emerge as individuals attempt to cope with T1D and related emotional distress. iACT taught acceptance and mindfulness as an alternative to maladaptive avoidance and control, and leveraged personal values to increase willingness to engage in T1D management, even when it was upsetting (e.g., after overeating). A tailored mobile application ("app") was used in between sessions to facilitate the application of ACT skills in the moment that individuals are making decisions about their diabetes management. METHODS: Adults with T1D who met criteria for an ED completed 12 sessions of iACT (with three optional tapering sessions). In addition to examining whether treatment was acceptable and feasible (the primary aim of the study), the study also examined whether iACT was associated with increased psychological flexibility (i.e., the ability to have distressing thoughts/feelings about diabetes while pursuing personally meaningful values), and improvements in ED symptoms, diabetes management and diabetes distress. RESULTS: Treatment was acceptable to T1D patients with EDs and feasible to implement. Participants reported increased psychological flexibility with diabetes-related thoughts/feelings, and less obstruction and greater progress in pursuing personal values. There were large effects for change in ED symptoms, diabetes self-management and diabetes distress from baseline to end-of-treatment (Cohen's d = .90-1.79). Hemoglobin A1c also improved, but the p-value did not reach statistical significance, p = .08. CONCLUSIONS: Findings provide preliminary evidence for iACT to improve outcomes for T1D patients with EDs and support further evaluation of this approach in a controlled trial. TRIAL REGISTRATION: NCT02980627 . Registered 8 July 2016.

Non-invasive wearables for remote monitoring of HbA1c and glucose variability: proof of concept.

INTRODUCTION: Diabetes prevalence continues to grow and there remains a significant diagnostic gap in one-third of the US population that has pre-diabetes. Innovative, practical strategies to improve monitoring of glycemic health are desperately needed. In this proof-of-concept study, we explore the relationship between non-invasive wearables and glycemic metrics and demonstrate the feasibility of using non-invasive wearables to estimate glycemic metrics, including hemoglobin A1c (HbA1c) and glucose variability metrics. RESEARCH DESIGN AND METHODS: We recorded over 25 000 measurements from a continuous glucose monitor (CGM) with simultaneous wrist-worn wearable (skin temperature, electrodermal activity, heart rate, and accelerometry sensors) data over 8-10 days in 16 participants with normal glycemic state and pre-diabetes (HbA1c 5.2-6.4). We used data from the wearable to develop machine learning models to predict HbA1c recorded on day 0 and glucose variability calculated from the CGM. We tested the accuracy of the HbA1c model on a retrospective, external validation cohort of 10 additional participants and compared results against CGM-based HbA1c estimation models. RESULTS: A total of 250 days of data from 26 participants were collected. Out of the 27 models of glucose variability metrics that we developed using non-invasive wearables, 11 of the models achieved high accuracy (<10% mean average per cent error, MAPE). Our HbA1c estimation model using non-invasive wearables data achieved MAPE of 5.1% on an external validation cohort. The ranking of wearable sensor's importance in estimating HbA1c was skin temperature (33%), electrodermal activity (28%), accelerometry (25%), and heart rate (14%). CONCLUSIONS: This study demonstrates the feasibility of using non-invasive wearables to estimate glucose variability metrics and HbA1c for glycemic monitoring and investigates the relationship between non-invasive wearables and the glycemic metrics of glucose variability and HbA1c. The methods used in this study can be used to inform future studies confirming the results of this proof-of-concept study.

Comparative risk of musculoskeletal adverse reactions among new users of dipeptidyl peptidase-4 inhibitors: A retrospective cohort study.

Background: The effects of dipeptidyl peptidase-4 inhibitors (DPP4Is) on joint pain have been controversial. Objective: To assess the comparative musculoskeletal (MSk) risk of DPP4Is vs. non-DPP4Is. Methods: This study used a national claims database from January 2007 to December 2014. Exposure included the initiation of DPP4Is against the initiation of non-DPP4Is: metformin, sulfonylureas, thiazolidinediones, meglitinides, and glucagonlike peptide-1 receptor agonists (GLP-1 RAs). Insulin was not included in this study. Outcomes were newly diagnosed MSk conditions (arthralgia, arthropathy, and rheumatoid arthritis or other inflammatory polyarthropathies). Individuals exposed to DPP4Is were matched to those exposed to non-DPP4Is using a propensity score (PS). Balance between the DPP4I's group and the non-DPP4I's group was assessed using standardized differences for both continuous and categorical variables. Cox regressions were used to estimate hazard ratios (HRs) for MSk conditions. Results: Among PS-matched cohorts, incidence rates (IRs) for MSk conditions did not differ between DPP4I initiators and non-DPP4I initiators (HR = 1.01, 95% CI: 0.97-1.05). After stratifying non-DPP4Is by drug class, the results still showed that DPP4I initiators had similar MSk risk when compared to initiators of metformin, sulfonylureas, meglitinides, and GLP-1 RAs. However, thiazolidinedione initiators had higher risk of MSk conditions than DPP4I initiators (HR = 1.05, 95% CI: 1.00-1.10). Conclusions: This head-to-head comparison study estimated comparative MSk risks among different antidiabetic drugs. The risk of MSk conditions among DPP4I initiators were not significantly higher than non-DPP4I initiators.

Time of Day When Type 1 Diabetes Patients With Eating Disorder Symptoms Most Commonly Restrict Insulin.

OBJECTIVE: Restricting insulin to lose weight is a significant problem in the clinical management of type 1 diabetes (T1D). Little is known about this behavior or how to effectively intervene. Identifying when insulin restriction occurs could allow clinicians to target typical high-risk times or formulate hypotheses regarding factors that influence this behavior. The current study investigated the frequency of insulin restriction by time of day. METHODS: Fifty-nine adults with T1D and eating disorder symptoms completed 72 hours of real-time reporting of eating and insulin dosing with continuous glucose monitoring. We used a generalized estimating equation model to test the global hypothesis that frequency of insulin restriction (defined as not taking enough insulin to cover food consumed) varied by time of day, and examined frequency of insulin restriction by hour. We also examined whether patterns of insulin restriction for 72 hours corresponded with patients' interview reports of insulin restriction for the past 28 days. RESULTS: Frequency of insulin restriction varied as a function of time (p = .016). Insulin restriction was the least likely in the morning hours (6:00-8:59 AM), averaging 6% of the meals/snacks consumed. Insulin restriction was more common in the late afternoon (3:00-5:59 PM), peaking at 29%. Insulin was restricted for 32% of the meals/snacks eaten overnight (excluding for hypoglycemia); however, overnight eating was rare. Insulin restriction was associated with higher 120-minute postprandial blood glucose (difference = 44.4 mg/dL, 95% confidence interval = 22.7-68.5, p < .001) and overall poorer metabolic control (r = 0.43-0.62, p's < .01). Patients reported restricting insulin for a greater percentage of meals and snacks for the past 28 days than during the 72 hour real-time assessment; however, the reports were correlated (Spearman's ρ = 0.46, p < .001) and accounted for similar variance in HbA1c (34% versus 35%, respectively). CONCLUSIONS: Findings suggest that insulin restriction may be less likely in the morning, and that late afternoon is a potentially important time for additional therapeutic support. Results also suggest that systematic clinical assessment and treatment of overnight eating might improve T1D management.

One-week glucose control via zero-order release kinetics from an injectable depot of glucagon-like peptide-1 fused to a thermosensitive biopolymer.

Stimulation of the glucagon-like peptide-1 (GLP1) receptor is a useful treatment strategy for type 2 diabetes because of pleiotropic effects, including the regulation of islet hormones and the induction of satiety. However, the native ligand for the GLP1 receptor has a short half-live owing to enzymatic inactivation and rapid clearance. Here, we show that a subcutaneous depot formed after a single injection of GLP1 recombinantly fused to a thermosensitive elastin-like polypeptide results in zero-order release kinetics and circulation times of up to 10 days in mice and 17 days in monkeys. The optimized pharmacokinetics leads to 10 days of glycemic control in three different mouse models of diabetes, as well as to the reduction of glycosylated hemoglobin levels and weight gain in ob/ob mice treated once weekly for 8 weeks. Our results suggest that the optimized GLP1 formulation could enhance therapeutic outcomes by eliminating peak-and-valley pharmacokinetics and improving overall safety and tolerability. The design principles that we established should be broadly applicable for improving the pharmacological performance of other peptide and protein therapeutics.

Effect of Intensive Versus Standard Blood Pressure Treatment According to Baseline Prediabetes Status: A Post Hoc Analysis of a Randomized Trial.

OBJECTIVE: To determine whether the effects of intensive (<120 mmHg) compared with standard (<140 mmHg) systolic blood pressure (SBP) treatment are different among those with prediabetes versus those with fasting normoglycemia at baseline in the Systolic Blood Pressure Intervention Trial (SPRINT). RESEARCH DESIGN AND METHODS: This was a post hoc analysis of SPRINT. SPRINT participants were categorized by prediabetes status, defined as baseline fasting serum glucose ≥100 mg/dL versus those with normoglycemia (fasting serum glucose <100 mg/dL). The primary outcome was a composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Cox regression was used to calculate hazard ratios for study outcomes with intensive compared with standard SBP treatment among those with prediabetes and normoglycemia. RESULTS: Among 9,361 participants randomized (age 67.9 ± 9.4 years; 35.5% female), 3,898 and 5,425 had baseline prediabetes and normoglycemia, respectively. After a median follow-up of 3.26 years, the hazard ratio for the primary outcome was 0.69 (95% CI 0.53, 0.89) and 0.83 (95% CI 0.66, 1.03) among those with prediabetes and normoglycemia, respectively (P value for interaction 0.30). For all-cause mortality, the hazard ratio with intensive SBP treatment was 0.77 (95% CI 0.55, 1.06) for prediabetes and 0.71 (95% CI 0.54, 0.94) for normoglycemia (P value for interaction 0.74). Effects of intensive versus standard SBP treatment on prespecified renal outcomes and serious adverse events were similar for prediabetes and normoglycemia (all interaction P > 0.05). CONCLUSIONS: In SPRINT, the beneficial effects of intensive SBP treatment were similar among those with prediabetes and fasting normoglycemia.

Technosphere insulin: inhaled prandial insulin.

INTRODUCTION: Insulin therapy is a mainstay for treatment of diabetes mellitus; however, many barriers to insulin exist. Insulin human inhalation powder (technosphere insulin) is a new FDA-approved alternative to subcutaneous bolus insulin. AREAS COVERED: This is an overview of technosphere insulin (TI). Pharmacokinetics, clinical efficacy, safety and tolerability are discussed. EXPERT OPINION: TI is more quickly absorbed than subcutaneous insulin therapies and has a shorter duration of action. It appears to be noninferior compared with subcutaneous insulin regimens, and is associated with less hypoglycemia. Thus, it may serve as an alternative insulin agent in patients reluctant to administer multiple subcutaneous injections of insulin daily or in patients who experience late postprandial hypoglycemia with subcutaneous insulin. Cough is the most common side effect, but tends to be mild and transient. A small decrease in the forced expiratory volume has been demonstrated, but does not appear to progress and is reversible. Patients should have periodic pulmonary function tests. TI is contraindicated in patients with chronic lung disease. The long-term risk of lung cancer is being monitored but at this point does not appear to be higher than the expected incidence of lung cancer in this population.

Forty-Year Trends in Tooth Loss Among American Adults With and Without Diabetes Mellitus: An Age-Period-Cohort Analysis.

INTRODUCTION: This study aimed to assess the trends in tooth loss among adults with and without diabetes mellitus in the United States and racial/ethnic disparities in tooth loss patterns, and to evaluate trends in tooth loss by age, birth cohorts, and survey periods. METHODS: Data came from 9 waves of the National Health and Nutrition Examination Survey (NHANES) from 1971 through 2012. The trends in the estimated tooth loss in people with and without diabetes were assessed by age groups, survey periods, and birth cohorts. The analytical sample was 37,609 dentate (ie, with at least 1 permanent tooth) adults aged 25 years or older. We applied hierarchical age-period-cohort cross-classified random-effects models for the trend analysis. RESULTS: The estimated number of teeth lost among non-Hispanic blacks with diabetes increased more with age than that among non-Hispanic whites with diabetes (z = 4.05, P < .001) or Mexican Americans with diabetes (z = 4.38, P < .001). During 1971-2012, there was a significant decreasing trend in the number of teeth lost among non-Hispanic whites with diabetes (slope = -0.20, P < .001) and non-Hispanic blacks with diabetes (slope = -0.37, P < .001). However, adults with diabetes had about twice the tooth loss as did those without diabetes. CONCLUSION: Substantial differences in tooth loss between adults with and without diabetes and across racial/ethnic groups persisted over time. Appropriate dental care and tooth retention need to be further promoted among adults with diabetes.

Momentary Predictors of Insulin Restriction Among Adults With Type 1 Diabetes and Eating Disorder Symptomatology.

OBJECTIVE: Individuals with type 1 diabetes who restrict insulin to control weight are at high risk for diabetes-related complications and premature death. However, little is known about this behavior or how to effectively intervene. The aim of the current study was to identify predictors of insulin restriction in the natural environment that might inform new treatment directions. RESEARCH DESIGN AND METHODS: Eighty-three adults with type 1 diabetes and a range of eating disorder symptomatology completed 3 days of ecological momentary assessment. Participants reported emotions, eating, and insulin dosing throughout the day using their cellular telephone. Linear mixed models were used to estimate the effects of heightened negative affect (e.g., anxiety) before eating and characteristics of the eating episode (e.g., eating a large amount of food) on the risk of insulin restriction. RESULTS: Individuals who reported greater-than-average negative affect (general negative affect and negative affect specifically about diabetes) during the study period were more likely to restrict insulin. Momentary increases in anxiety/nervousness and guilt/disgust with self before eating (relative to an individual's typical level) further increased the odds of restricting insulin at the upcoming meal. Insulin restriction was more likely when individuals reported that they broke a dietary rule (e.g., "no desserts"). CONCLUSIONS: Results suggest that insulin restriction might be decreased by helping patients with type 1 diabetes respond effectively to heightened negative affect (e.g., anxiety, guilt) and encouraging patients to take a less rigid, punitive approach to diabetes management.

The Effect of Blood Glucose Self-Monitoring Among Inmates With Diabetes.

The increasing prevalence and risk of complications from diabetes necessitate patient participation and attentiveness to select appropriate foods, perform regular physical activity, and be active in diabetes management and self-maintenance. Diabetes is often largely asymptomatic; consequently, early diagnosis and treatment are necessary. Inmates are a unique population challenged by the increased prevalence of chronic conditions including diabetes. Diabetes standards for inmates contain diagnostic and treatment management guidelines that incorporate personal glucose monitoring for insulin users. In December 2009, the Federal Bureau of Prisons initiated a program to distribute glucose meters to insulin-dependent inmates to facilitate self-monitoring blood glucose. The purpose of this study was to evaluate the effect of these glucose meters on hemoglobin A1c levels.

Education, glucose control, and mortality risks among U.S. older adults with diabetes.

AIMS: Studies have shown that diabetes mellitus disproportionately afflicts persons of low socioeconomic status and that the burden of disease is greatest among the disadvantaged. However, our understanding of educational differences in the control of diabetes and its impact on survival is limited. This study investigated the associations among education, hemoglobin A1c (HbA1c), and subsequent mortality in adults with diabetes. METHODS: Prospective cohort data from the 2006, 2008, and 2010 Health and Retirement Study were linked with biomarker data for U.S. older adults with diabetes (n=3312). Weighted distributions were estimated for all subjects at baseline and by the American Diabetes Association's general guidelines for HbA1c control (<7.0% [53 mmol/mol] vs. ≥7.0% [53 mmol/mol]). Proportional hazard models were used to estimate educational differences in all-cause mortality by HbA1c level with sequential adjustments for contributing risk factors. RESULTS: Mortality risks associated with HbA1c≥7.0% [53 mmol/mol] were significantly greater in lower-educated adults than higher-educated adults (P<0.001). We found that the hazard ratios (HR) associated with HbA1c ≥7.0% [53 mmol/mol] were highest among low-educated adults (HR=2.18, 95% CI: 1.62, 2.94) and that a combination of socioeconomic, psychosocial, and behavioral factors accounted for most, but not all, of the associations. CONCLUSIONS: Educational differences in HbA1c control have significant implications for mortality and efforts to reduce these disparities should involve more vigilant screening and monitoring of lower-educated adults with diabetes.

Methods and initial findings from the Durham Diabetes Coalition: Integrating geospatial health technology and community interventions to reduce death and disability.

OBJECTIVE: The Durham Diabetes Coalition (DDC) was established in response to escalating rates of disability and death related to type 2 diabetes mellitus, particularly among racial/ethnic minorities and persons of low socioeconomic status in Durham County, North Carolina. We describe a community-based demonstration project, informed by a geographic health information system (GHIS), that aims to improve health and healthcare delivery for Durham County residents with diabetes. MATERIALS AND METHODS: A prospective, population-based study is assessing a community intervention that leverages a GHIS to inform community-based diabetes care programs. The GHIS integrates clinical, social, and environmental data to identify, stratify by risk, and assist selection of interventions at the individual, neighborhood, and population levels. RESULTS: The DDC is using a multifaceted approach facilitated by GHIS to identify the specific risk profiles of patients and neighborhoods across Durham County. A total of 22,982 patients with diabetes in Durham County were identified using a computable phenotype. These patients tended to be older, female, African American, and not covered by private health insurance, compared with the 166,041 persons without diabetes. Predictive models inform decision-making to facilitate care and track outcomes. Interventions include: 1) neighborhood interventions to improve the context of care; 2) intensive team-based care for persons in the top decile of risk for death or hospitalization within the coming year; 3) low-intensity telephone coaching to improve adherence to evidence-based treatments; 4) county-wide communication strategies; and 5) systematic quality improvement in clinical care. CONCLUSIONS: To improve health outcomes and reduce costs associated with type 2 diabetes, the DDC is matching resources with the specific needs of individuals and communities based on their risk characteristics.

Barriers to care for patients with diabetes in Durham, North Carolina, why are we withholding life-sustaining medications from the patients who need them the most?

The diabetes epidemic and its complications disproportionately affect minorities and the poor. Medical treatments that can prevent or delay diabetes complications are widely available but poverty underlies much of why there are disparities in diabetes care and outcomes. Lack of access to care, food insecurity and inability to pay for medications prevents adherence to a medication and lifestyle regimen that can be life-sustaining. At the very least, US policies should be changed to provide life-sustaining medications that prevent costly complications to patients who cannot afford them. Adopting value-based insurance design would benefit patients with diabetes who cannot afford to pay for medications but would also reduce healthcare costs in the long run.

HARMONY 3: 104-week randomized, double-blind, placebo- and active-controlled trial assessing the efficacy and safety of albiglutide compared with placebo, sitagliptin, and glimepiride in patients with type 2 diabetes taking metformin.

OBJECTIVE: To compare the efficacy and safety of weekly albiglutide with daily sitagliptin, daily glimepiride, and placebo. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes receiving metformin were randomized to albiglutide (30 mg), sitagliptin (100 mg), glimepiride (2 mg), or placebo. Blinded dose titration for albiglutide (to 50 mg) and glimepiride (to 4 mg) was based on predefined hyperglycemia criteria. The primary end point was change in HbA1c from baseline at week 104. Secondary end points included fasting plasma glucose (FPG), weight, and time to hyperglycemic rescue. RESULTS: Baseline characteristics were similar among the albiglutide (n = 302), glimepiride (n = 307), sitagliptin (n = 302), and placebo (n = 101) groups. Baseline HbA1c was 8.1% (65.0 mmol/mol); mean age was 54.5 years. The mean doses for albiglutide and glimepiride at week 104 were 40.5 and 3.1 mg, respectively. At week 104, albiglutide significantly reduced HbA1c compared with placebo (-0.9% [-9.8 mmol/mol]; P < 0.0001), sitagliptin (-0.4% [-4.4 mmol/mol]; P = 0.0001), and glimepiride (-0.3% [-3.3 mmol/mol]; P = 0.0033). Outcomes for FPG and HbA1c were similar. Weight change from baseline for each were as follows: albiglutide -1.21 kg (95% CI -1.68 to -0.74), placebo -1.00 kg (95% CI -1.81 to -0.20), sitagliptin -0.86 kg (95% CI -1.32 to -0.39), glimepiride 1.17 kg (95% CI 0.70-1.63). The difference between albiglutide and glimepiride was statistically significant (P < 0.0001). Hyperglycemic rescue rate at week 104 was 25.8% for albiglutide compared with 59.2% (P < 0.0001), 36.4% (P = 0.0118), and 32.7% (P = 0.1504) for placebo, sitagliptin, and glimepiride, respectively. Rates of serious adverse events in the albiglutide group were similar to comparison groups. Diarrhea (albiglutide 12.9%, other groups 8.6-10.9%) and nausea (albiglutide 10.3%, other groups 6.2-10.9%) were generally the most frequently reported gastrointestinal events. CONCLUSIONS: Added to metformin, albiglutide was well tolerated; produced superior reductions in HbA1c and FPG at week 104 compared with placebo, sitagliptin, and glimepiride; and resulted in weight loss compared with glimepiride.

Feasibility and preliminary effects of a virtual environment for adults with type 2 diabetes: pilot study.

BACKGROUND: Innovative interventions that empower patients in diabetes self-management (DSM) are needed to provide accessible, sustainable, cost-effective patient education and support that surpass current noninteractive interventions. Skills acquired in digital virtual environments (VEs) affect behaviors in the physical world. Some VEs are programmed as real-time three-dimensional representations of various settings via the Internet. For this research, a theoretically grounded VE that facilitates DSM was developed and pilot tested. It offered weekly synchronous DSM education classes, group meetings, and social networking in a community in which participants practiced real world skills such as grocery shopping, exercising, and dining out, allowing for interactive knowledge application. The VE was available 24/7 on the Internet, minimizing access barriers. OBJECTIVE: The objective of this study was to evaluate the feasibility and efficacy of participation in a VE for DSM education and support. METHODS: This study utilized a single group, pre-mid-post measure design. At 0, 3, and 6 months, we assessed participants' perceived VE usability and usefulness, self-efficacy, diabetes self-management behaviors, perceived social support, and diabetes knowledge using validated survey measures; and we recorded metabolic indicators (HbA1c, BP, BMI). Process data were continuously collected in the VE (log-ins, voice recordings, locations visited, objects interacted with, and movement). Data analysis included descriptive statistics, t tests to evaluate changes in mediators and outcomes over time, and depiction of utilization and movement data. RESULTS: We enrolled 20 participants (13/20, 65% white, 7/20, 35% black), with an age range of 39-72 years (mean age, 54 years) and diabetes duration from 3 months to 25 years. At baseline, 95% (18/19) and 79% (15/19) of participants rated usefulness and ease of use as high on validated surveys with no significant changes at 3 or 6 months. Participants logged into the site a mean of 2.5 hours/week over the course of 6 months. High DSM class attendance was reflected by the largest percentage of time spent in the classroom (48.6%). Self-efficacy, social support, and foot care showed significant improvement (P<.05). There were improvement trends in clinical outcomes that were clinically meaningful but did not reach statistical significance given the small sample size. CONCLUSIONS: Because relatively little is known about usability, acceptability, and efficacy of health interventions in VEs, this study constitutes an important, innovative first step in exploring the potential of VEs for facilitating DSM. The preliminary data suggest that VEs provide a feasible and useful platform for patients and educators that affects self-management and related mediators. Flexible access to both synchronous and asynchronous diabetes education, skill building activities, and support from a home computer remove barriers to attending clinic-based meetings. This program has potential for improving DSM in an easily disseminated alternative model.

Once-weekly albiglutide versus once-daily liraglutide in patients with type 2 diabetes inadequately controlled on oral drugs (HARMONY 7): a randomised, open-label, multicentre, non-inferiority phase 3 study.

BACKGROUND: As new members of a drug class are developed, head-to-head trials are an important strategy to guide personalised treatment decisions. We assessed two glucagon-like peptide-1 receptor agonists, once-weekly albiglutide and once-daily liraglutide, in patients with type 2 diabetes inadequately controlled on oral antidiabetic drugs. METHODS: We undertook this 32-week, open-label, phase 3 non-inferiority study at 162 sites in eight countries: USA (121 sites), Australia (9 sites), Peru (7 sites), Philippines (7 sites), South Korea (5 sites), UK (5 sites), Israel (4 sites), and Spain (4 sites). 841 adult participants (aged ≥18 years) with inadequately controlled type 2 diabetes and a BMI between 20 and 45 kg/m(2) were enrolled and randomised in a 1:1 ratio to receive albiglutide 30 mg once weekly titrated to 50 mg at week 6, or liraglutide 0·6 mg once daily titrated to 1·2 mg at week 1 and 1·8 mg at week 2. The randomisation schedule was generated by an independent randomisation team by the permuted block method with a fixed block size of 16. Participants and investigators were unmasked to treatment. The primary endpoint was change from baseline in HbA1c for albiglutide versus liraglutide, with a 95% CI non-inferiority upper margin of 0·3%. The primary analysis was by modified intention to treat. The study is registered with ClinicalTrials.gov, number NCT01128894. FINDINGS: 422 patients were randomly allocated to the albigultide group and 419 to the liraglutide group; 404 patients in the abliglutide group and 408 in the liraglutide group received the study drugs. The primary endpoint analysis was done on the modified intention-to-treat population, which included 402 participants in the albiglutide group and 403 in the liraglutide group. Model-adjusted change in HbA1c from baseline to week 32 was -0·78% (95% CI -0·87 to -0·69) in the albigludite group and -0·99% (-1·08 to -0·90) in the liraglutide group; treatment difference was 0·21% (0·08-0·34; non-inferiority p value=0·0846). Injection-site reactions occurred in more patients given albiglutide than in those given liraglutide (12·9% vs 5·4%; treatment difference 7·5% [95% CI 3·6-11·4]; p=0·0002), whereas the opposite was the case for gastrointestinal events, which occurred in 49·0% of patients in the liraglutide group versus 35·9% in the albiglutide group (treatment difference -13·1% [95% CI -19·9 to -6·4]; p=0·00013). INTERPRETATION: Patients who received once-daily liraglutide had greater reductions in HbA1c than did those who received once-weekly albiglutide. Participants in the albiglutide group had more injection-site reactions and fewer gastrointestinal events than did those in the liraglutide group. FUNDING: GlaxoSmithKline.