Addressing the Burden of Multiple Daily Insulin Injections in Type 2 Diabetes with Insulin Pump Technology: A Narrative Review.

The growing prevalence of type 2 diabetes (T2D) remains a leading health concern in the US. Despite new medications and technologies, glycemic control in this population remains suboptimal, which increases the risk of poor outcomes, increased healthcare resource utilization, and associated costs. This article reviews the clinical and economic impacts of suboptimal glycemic control in patients on basal-bolus insulin or multiple daily injections (MDI) and discusses how new technologies, such as tubeless insulin delivery devices, referred to as "patch pumps", have the potential to improve outcomes in patients with T2D.

Prioritizing Patient Experiences in the Management of Diabetes and Its Complications: An Endocrine Society Position Statement.

Diabetes can be an arduous journey both for people with diabetes (PWD) and their caregivers. While the journey of every person with diabetes is unique, common themes emerge in managing this disease. To date, the experiences of PWD have not been fully considered to successfully implement the recommended standards of diabetes care in practice. It is critical for health-care providers (HCPs) to recognize perspectives of PWD to achieve optimal health outcomes. Further, existing tools are available to facilitate patient-centered care but are often underused. This statement summarizes findings from multistakeholder expert roundtable discussions hosted by the Endocrine Society that aimed to identify existing gaps in the management of diabetes and its complications and to identify tools needed to empower HCPs and PWD to address their many challenges. The roundtables included delegates from professional societies, governmental organizations, patient advocacy organizations, and social enterprises committed to making life better for PWD. Each section begins with a clinical scenario that serves as a framework to achieve desired health outcomes and includes a discussion of resources for HCPs to deliver patient-centered care in clinical practice. As diabetes management evolves, achieving this goal will also require the development of new tools to help guide HCPs in supporting PWD, as well as concrete strategies for the efficient uptake of these tools in clinical practice to minimize provider burden. Importantly, coordination among various stakeholders including PWD, HCPs, caregivers, policymakers, and payers is critical at all stages of the patient journey.

A Glycemia Risk Index (GRI) of Hypoglycemia and Hyperglycemia for Continuous Glucose Monitoring Validated by Clinician Ratings.

BACKGROUND: A composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data. METHODS: We assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation. RESULTS: The analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals. CONCLUSION: The GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.

Practical Strategies to Help Reduce Added Sugars Consumption to Support Glycemic and Weight Management Goals.

Overconsumption of added sugars is a key contributor to the growing obesity, prediabetes, and type 2 diabetes pandemics. The nutrition therapy guidance of the American Diabetes Association recognizes that using low- and no-calorie sweeteners (LNCS) to reduce consumption of added sugars can reduce low-nutrient-density sources of calories and carbohydrate to beneficially affect glycemia, weight, and cardiometabolic health. This article provides information for primary care providers, diabetes care and education specialists, and other diabetes clinicians on the safety of LNCS and summarizes research evidence on the role of LNCS in glycemic and weight management. It also provides practical strategies for counseling individuals about how to integrate LNCS into their healthy eating pattern.

Utilizing continuous glucose monitoring in primary care practice: What the numbers mean.

Use of continuous glucose monitoring (CGM) has been shown to improve glycemia control, reduce hypoglycemia, lower glycemic variability and enhance quality of life for individuals with type 1 diabetes and type 2 diabetes. However, many primary care physicians may be unfamiliar with the how CGM data can interpreted and acted upon. As adoption of this technology continues to grow, primary care physicians will be challenged to integrate CGM into their clinical practices. This article is intended to provide clinicians with practical guidance in interpreting and utilizing CGM data with their patients.

Demographic characteristics and acute complications among adults with type 1 diabetes: Comparison of two multicentre databases from Germany and the United States.

BACKGROUND: Studies on acute complications in adult T1D were previously reported from the United States (U.S.) and from Germany. The aim was to compare demographic characteristics and patterns of severe hypoglycaemia (SH) and diabetic ketoacidosis (DKA) between Germany and the U.S. METHODS: Descriptive comparison on individuals aged ≥18 years, with T1D duration ≥2 years were made between the German diabetes-patient registry (DPV) and the U.S. electronic-health-record database (T1PCO). Individuals in both databases were divided into patients with haemoglobin A1c (HbA1c) <7% and HbA1c ≥7%. RESULTS: 5190 (DPV) and 31,430 individuals (T1PCO) fulfilled the inclusion criteria. DPV patients were younger, more often male and had lower body-mass index. In both databases, more males than females had HbA1c <7%. Individuals had higher HbA1c in T1PCO compared to DPV. The relationship between HbA1c and DKA was similar in both databases. SH revealed a U-shaped curve in T1PCO, but no clear pattern was present in DPV. SH events increased with higher age in DPV, but not in T1PCO. CONCLUSION: Patterns of SH differ between Germany and U.S. Differences in capture of SH among the databases cannot be excluded, but differences in health care including patient education and level of care by specialists are likely.

Comparison of Second-Generation Basal Insulin Analogs: A Review of the Evidence from Continuous Glucose Monitoring.

Many people with insulin-treated diabetes continue to experience inadequate glycemic control and a high incidence of hypoglycemic events, despite improvements in therapeutic strategies. While glycated hemoglobin (HbA1c) is currently recognized as the gold-standard for assessing glycemic control, the measure reflects mean blood glucose levels over a period of time, does not inform on acute glycemic deviations, and can be unreliable in certain populations. Continuous glucose monitoring (CGM) facilitates the acquisition of blood glucose data around the clock and, importantly, predicts and/or captures acute hyper- and hypoglycemic episodes. In light of the recent publication of the Time in Range (TIR) International Consensus Group report on key CGM metrics, we performed a review of current CGM evidence for second-generation basal insulins in both people with type 1 and type 2 diabetes. The identified studies highlight the varied CGM-related metrics used to assess basal insulins, which complicate comparisons. Furthermore, all studies had small sample sizes and typically were of short duration, which may account for the lack of statistically significant between-treatment differences observed. Differences were seen in the titration approaches used and the settings in which participants were observed. These results highlight the need for further studies of second-generation basal insulin analogs that are designed to capture the standard metrics proposed by the TIR consensus group, with additional consideration given to sample size and study duration.

Patients With Type 2 Diabetes Are Willing to Do More to Overcome Therapeutic Inertia: Results From a Double-Blind Survey.

We performed a survey of 305 patients with type 2 diabetes receiving basal insulin and 240 physicians to measure key contrasts and similarities in patients' preferences and providers' beliefs and perceptions regarding insulin use. Many patients reported being more frustrated with their lack of treatment progress than physicians were aware of. Patients were also more likely to say they would do more than their physicians believed they would to better manage their diabetes. Identifying priorities and setting clear goals and timelines for achieving glycemic control could provide an opportunity to address these differences and reduce patients' frustration.

Differences between patients with type 1 diabetes with optimal and suboptimal glycaemic control: A real-world study of more than 30 000 patients in a US electronic health record database.

AIMS: To use electronic health record data from real-world clinical practice to assess demographics, clinical characteristics and disease burden of adults with type 1 diabetes (T1D) in the United States. MATERIALS AND METHODS: Retrospective observational study of adults with T1D for ≥24 months at their first visit with a T1D diagnosis code ("index date") between July 2014 and June 2016 in the Optum Humedica database. Demographic characteristics, acute complications (severe hypoglycaemia [SH], diabetic ketoacidosis [DKA]), microvascular complications, cardiovascular (CV) events and health care resource utilization during the 12 months before the index date ("baseline period") were compared between patients with optimal versus suboptimal glycaemic control (glycated haemoglobin [HbA1c] <7.0% vs. ≥7.0% [53 mmol/mol]) at the closest measurement to the index date. RESULTS: Of 31 430 adults with T1D, 79.9% had suboptimal glycaemic control (mean HbA1c 8.8% [73 mmol/mol]). These patients were more likely to be younger, African American, uninsured or on Medicaid, obese, smokers, have uncontrolled hypertension and have depression. Despite worse glycaemic control and increased CV risk factors of uncontrolled hypertension, obesity and smoking, rates of coronary heart disease and stroke were not higher in these patients. Patients with suboptimal glycaemic control also experienced more diabetes complications (including SH, DKA and microvascular disease) and utilized more emergency care, with more emergency department visits and inpatient stays. CONCLUSION: This real-world study of >30 000 adults with T1D showed that individuals with suboptimal versus optimal glycaemic control differed significantly in terms of health care coverage, comorbidities, diabetes-related complications, health care utilization and CV risk factors. However, suboptimal control was not associated with increased risk of CV outcomes.

Persistence with Basal-Bolus Insulin Therapy in Patients with Type 2 Diabetes Mellitus and Effect on Clinical and Economic Outcomes: A Retrospective Claims Database Study.

BACKGROUND: Persistence with multiple daily insulin injections (MDI) may be challenging for patients with type 2 diabetes (T2DM). However, limited information is available regarding the effect of persistence with MDI on outcomes. OBJECTIVE: To evaluate persistence with basal and bolus insulin therapy and assess its relationship with clinical and economic outcomes in a real-world setting. METHODS: This retrospective matched cohort study used 2012-2015 data from multiple U.S. commercial health plans (IBM MarketScan). Patients with T2DM aged 18-64 years with ≥ 2 basal and ≥ 2 bolus insulin claims during a 12-month period were eligible for inclusion if they had 18 months of continuous health plan enrollment (6-month baseline and 12-month post-index). Persistence during 12 months post-index was defined using 2 methods: (a) method 1, ≤ 90-day gaps in both basal and bolus insulin claims and (b) method 2, ≥ 1 basal and ≥ 1 bolus insulin claim every quarter (every 90 days) for 4 consecutive quarters after index bolus claim. Propensity score matching was used to match persistent and nonpersistent method 2 cohorts. Mean per-patient all-cause and diabetes-related medical costs (2015 U.S. dollars, excluding outpatient drugs) and health care resource use (HCRU) were calculated. For patients with hemoglobin A1c (A1c) values during baseline and post-index months 10-12, treatment success was defined as (a) A1c decrease from baseline of ≥ 1% and/or (b) baseline A1c ≥ 7% with post-index A1c < 7%. Baseline characteristics of matched cohorts were compared using standardized mean differences (SMDs). Outcome variables were compared using t-tests, chi-square tests, and generalized linear models. RESULTS: Characteristics of 12,882 eligible patients and 12-month persistence rates were similar as defined by method 1 (22.4%) and method 2 (21.1%). After matching, the method 2 cohorts included 2,723 and 8,169 persistent and nonpersistent patients, respectively, with well-balanced baseline characteristics (mean age 53 years; 58% men; all SMDs < 0.1). All-cause annual medical costs were lower for the persistent cohort (mean $13,499 vs. $17,362; P < 0.0001), as were annual diabetes-related costs (mean $6,392 vs. $8,376; P < 0.0001). In persistent versus nonpersistent cohorts, 11% versus 15% of patients, respectively, experienced ≥ 1 hospitalization; 21% versus 24%, respectively, had ≥ 1 ED visit; 9% versus 12%, respectively, experienced ≥ 1 diabetes-related hospitalization; and 13% versus 15%, respectively, had ≥ 1 diabetes-related ED visit (P ≤ 0.005 for all). Mean baseline A1c was similar in persistent and nonpersistent cohorts (9.7% vs. 9.6%, respectively; P = 0.63). Persistence with MDI was associated with greater mean reduction in A1c (-1.3% vs. -0.8%, respectively; P = 0.006) and greater percentages of patients achieving treatment success (55% vs. 39%, respectively, for nonpersistent; P = 0.009). CONCLUSIONS: Poor persistence with basal-bolus insulin therapy over 12 months of follow-up was prevalent and was associated with greater medical costs, greater HCRU, and poorer glycemic control than for patients who were persistent. Interventions are needed to improve persistence with insulin therapy and aid patients with T2DM to achieve glycemic control. DISCLOSURES: Funding for this study was provided by Becton, Dickinson and Company (BD). All authors except Edelman are employees and stockholders of BD. Edelman reports board membership at Senseonics and participation in advisory board/speakers bureau at Lilly USA, MannKind, Novo Nordisk, Sanofi-Aventis U.S., Merck, and AstraZeneca, all unrelated to this study. A poster for this study was presented at the AMCP Managed Care & Specialty Pharmacy Annual Meeting 2018; April 23-26, 2018; Boston MA.

Incidences of Severe Hypoglycemia and Diabetic Ketoacidosis and Prevalence of Microvascular Complications Stratified by Age and Glycemic Control in U.S. Adult Patients With Type 1 Diabetes: A Real-World Study.

OBJECTIVE: To assess the burden of disease for adults with type 1 diabetes in a U.S. electronic health record database by evaluating acute and microvascular complications stratified by age and glycemic control. RESEARCH DESIGN AND METHODS: This is a retrospective observational study of adults with type 1 diabetes (1 July 2014-30 June 2016) classified using a validated algorithm, with disease duration ≥24 months and, during a 12-month baseline period, not pregnant and having one or more insulin prescriptions and one or more HbA1c measurements. Demographic characteristics, acute complications (severe hypoglycemia [SH], diabetic ketoacidosis [DKA]), and microvascular complications (neuropathy, nephropathy, retinopathy) were stratified by age (18-25, 26-49, 50-64, ≥65 years) and glycemic control (HbA1c <7%, 7% to <9%, ≥9%). RESULTS: Of 31,430 patients, ∼20% had HbA1c <7%. Older patients had lower HbA1c values than younger patients (P < 0.001). Patients with poor glycemic control had the highest annual incidence of SH (4.2%, 4.0%, and 8.3%) and DKA (1.3%, 2.8%, and 15.8%) for HbA1c <7%, 7% to <9%, and ≥9% cohorts, respectively (both P < 0.001), and a higher prevalence of neuropathy and nephropathy (both P < 0.001). CONCLUSIONS: For adults with type 1 diabetes, glycemic control appears worse than previously estimated. Rates of all complications increased with increasing HbA1c. Compared with HbA1c <7%, HbA1c ≥9% was associated with twofold and 12-fold higher incidences of SH and DKA, respectively. Younger adults had more pronounced higher risks of SH and DKA associated with poor glycemic control than older adults.

Sodium-glucose co-transporter inhibitors as adjunctive treatment to insulin in type 1 diabetes: A review of randomized controlled trials.

Many patients with type 1 diabetes (T1D) struggle to achieve glycaemic control and experience significant fluctuations in glucose concentrations, despite insulin treatment. Sodium-glucose co-transporter (SGLT)-2 inhibitors and dual SGLT-1/2 inhibitors increase glucose elimination via the kidneys and reduce hyperglycaemia via insulin-independent mechanisms. This review examines available efficacy and safety data for these agents under investigation as adjunctive therapy for T1D. Across randomized trials of up to 52 weeks, SGLT-2 inhibitors or SGLT-1/2 inhibitors as an adjunct to insulin demonstrated significant reductions in glycated haemoglobin, glucose exposure, and measures of glycaemic variability, as well as increased time in the target glycaemic range, compared with placebo. Non-glycaemic benefits included reductions in body weight and insulin doses, as well as improvements in some cardiovascular risk factors and treatment satisfaction. SGLT-2 inhibitors and SGLT-1/2 inhibitors were associated with similar rates of hypoglycaemia but a higher incidence of genitourinary infections, compared with placebo. Diabetic ketoacidosis occurred more often with SGLT-2 inhibitors and SGLT-1/2 inhibitors vs placebo, although the incidence was generally low. Risk mitigation strategies in light of clinical trial data are also discussed. Positive data from randomized controlled trials of the SGLT-2 inhibitor dapagliflozin have led to the approval of dapagliflozin as an adjunct to insulin in adults with T1D having body mass index ≥27 kg/m2 in whom insulin does not provide adequate glycaemic control in Europe and to approval as an adjunct to insulin for adults with T1D in Japan.

Clinical Implications of Real-time and Intermittently Scanned Continuous Glucose Monitoring.

Two types of continuous glucose monitoring (CGM) systems are now available: real-time CGM (rtCGM) and intermittently scanned (isCGM). Current rtCGM systems automatically transmit a continuous stream of glucose data to the user, provide alerts and active alarms, and transmit glucose data (trend and numerical) in real time to a receiver, smart watch, or smartphone. The current isCGM system provides the same type of glucose data but requires the user to purposely scan the sensor to obtain information, and it does not have alerts and alarms. Both CGM technologies have significant advantages over self-monitoring of blood glucose; however, differences in the features and capabilities of the two approaches must be considered when guiding patient selection of the system that meets their individual needs.

Recommendations for Initiating Use of Afrezza Inhaled Insulin in Individuals with Type 1 Diabetes.

Treatment with Afrezza® (insulin human) inhalation powder in individuals with type 1 diabetes (T1D) reduces HbA1c levels similar to rapid-acting insulin analogs, but with significantly less hypoglycemia due to its unique time action profile. Examinations of studies of Afrezza pharmacokinetics/pharmacodynamics, relevant clinical trials, and U.S. Food and Drug Administration (FDA) documentation suggest that current FDA-mandated dosing recommendations for initiating Afrezza treatment may not result in optimal glycemic control for individuals with T1D. Recommendations for initiating Afrezza insulin therapy in T1D patients are presented in this article.

Type 2 Diabetes in the Real World: The Elusive Nature of Glycemic Control.

Despite U.S. Food and Drug Administration (FDA) approval of over 40 new treatment options for type 2 diabetes since 2005, the latest data from the National Health and Nutrition Examination Survey show that the proportion of patients achieving glycated hemoglobin (HbA1c) <7.0% (<53 mmol/mol) remains around 50%, with a negligible decline between the periods 2003-2006 and 2011-2014. The Healthcare Effectiveness Data and Information Set reports even more alarming rates, with only about 40% and 30% of patients achieving HbA1c <7.0% (<53 mmol/mol) in the commercially insured (HMO) and Medicaid populations, respectively, again with virtually no change over the past decade. A recent retrospective cohort study using a large U.S. claims database explored why clinical outcomes are not keeping pace with the availability of new treatment options. The study found that HbA1c reductions fell far short of those reported in randomized clinical trials (RCTs), with poor medication adherence emerging as the key driver behind the disconnect. In this Perspective, we examine the implications of these findings in conjunction with other data to highlight the discrepancy between RCT findings and the real world, all pointing toward the underrealized promise of FDA-approved therapies and the critical importance of medication adherence. While poor medication adherence is not a new issue, it has yet to be effectively addressed in clinical practice-often, we suspect, because it goes unrecognized. To support the busy health care professional, innovative approaches are sorely needed.

Understanding the Gap Between Efficacy in Randomized Controlled Trials and Effectiveness in Real-World Use of GLP-1 RA and DPP-4 Therapies in Patients With Type 2 Diabetes.

OBJECTIVE: The objective of this study was to estimate and explain the gap between clinical efficacy and real-world (RW) effectiveness of type 2 diabetes medications. RESEARCH DESIGN AND METHODS: This mixed-methods quasi-experimental study used retrospective claims (Optum/Humedica) to compare the change in HbA1c of RW patients with type 2 diabetes 12 months after starting a glucagon-like peptide 1 receptor agonist (GLP-1 RA) or dipeptidyl peptidase 4 (DPP-4) inhibitor with published findings from randomized controlled trials (RCTs) evaluating these drugs. Selected RW patients were similar to RCT patients, and regression analysis was used in the RW data to adjust for differences between poorly adherent and adherent patients to explain why RCT and RW findings may differ. RESULTS: RW patients initiating a GLP-1 RA (n = 221) or a DPP-4 (n = 652) experienced smaller reductions in HbA1c (GLP-1 RA: -0.52% [-6 mmol/mol], DPP-4: -0.51% [-6 mmol/mol])than reported in RCTs (-1.30% [-14 mmol/mol] from seven GLP-1 RA RCTs, n = 2,600; -0.68% [-8 mmol/mol] from four DPP-4 RCTs, n = 1,889). Baseline HbA1c, additional medications, and adherence were significant explanatory factors in the RW HbA1c change. Modeled estimates of RCT efficacy (-1.04% GLP-1 RA [-12 mmol/mol], -0.69% DPP-4 [-8 mmol/mol]) were within the RCTs' reported range (GLP-1 RA: -0.84% to -1.60% [-9 to -18 mmol/mol], DPP-4: -0.47% to -0.90% [-5 to -10 mmol/mol]). Poor medication adherence accounted for approximately three-fourths of the gap between RW and expected RCT results (gap = 0.51% [6 mmol/mol] GLP-1 RA; 0.18% [3 mmol/mol] DPP-4). CONCLUSIONS: Poor medication adherence is primarily why RW effectiveness is significantly less than RCT efficacy, suggesting an urgent need to effectively address adherence among patients with type 2 diabetes.

Achievement of Glycated Hemoglobin Goals in the US Remains Unchanged Through 2014.

INTRODUCTION: Previous research has found that the percentage of US adults with diabetes achieving a glycated hemoglobin (HbA1c) target of <7.0% with currently available treatments has been fairly constant from 2003 to 2010, remaining at just over 50% [1]. The objective of this study was to compare the most recent data (2011-2014) with earlier data to track progress on HbA1c target achievement, for both the general target of <7.0% and inferred individualized targets based on age and the presence of complications. METHODS: Data from 2677 adults with self-reported diabetes from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2014 were examined to determine the percentage of adults who achieved HbA1c targets of <7% and an individualized target based on age and comorbidities. National estimates are reported by using weights that account for the complex sampling design of the NHANES. RESULTS: The percentage of people with diabetes and HbA1c <7.0% slightly declined from 52.2% (95% CI 48.7-55.7%) to 50.9% (95% CI 47.2-54.7%) between the two most recent waves of data. Achievement of individualized targets declined from 69.8% (95% CI 66.5-73.0%) to 63.8% (95% CI 60.1-67.5%). The percentage with HbA1c >9.0% increased from 12.6% (95% CI 10.5-14.8%) to 15.5% (95% CI 12.9-18.2%). Achievement of individualized targets varied by age group and presence of comorbidities, but exhibited similar trends as general target achievement. CONCLUSIONS: Despite the development of many new medications to treat diabetes during the past decade, the proportion of patients achieving glycemic control targets has not improved. FUNDING: Intarcia Therapeutics.

Where Are We Now? A Clinicians' Guide to the Use of Follow-On Insulin for Patients with Diabetes.

Insulin has been used as a standard treatment for patients with diabetes for almost 100 years. Over time, advances in insulin development have improved its pharmacologic properties. (Online access: http://courses.elseviercme.com/t2dm/666). Most recently, the US Food and Drug Administration approved a novel, follow-on basal insulin agent, with more expected to be commercially available in the near future. With the imminent availability of follow-on basal insulin agents, clinicians need to be aware of the potential benefits and concerns in order to facilitate informed decision making and to provide the best possible advice and guidance to their patients with diabetes. This program will review how follow-on insulin products are developed, manufactured, and receive regulatory approval; evaluate clinical trial data for new and emerging follow-on basal insulin agents; and provide practical information and guidance on how they may be incorporated into clinical practice. While it is unknown how follow-on basal insulins will affect patient outcomes, they have the potential to increase access to treatment among patients with diabetes and reduce healthcare costs.