Diabetes Care Editors' Expert Forum 2018: Managing Big Data for Diabetes Research and Care.

Technological progress in the past half century has greatly increased our ability to collect, store, and transmit vast quantities of information, giving rise to the term "big data." This term refers to very large data sets that can be analyzed to identify patterns, trends, and associations. In medicine-including diabetes care and research-big data come from three main sources: electronic medical records (EMRs), surveys and registries, and randomized controlled trials (RCTs). These systems have evolved in different ways, each with strengths and limitations. EMRs continuously accumulate information about patients and make it readily accessible but are limited by missing data or data that are not quality assured. Because EMRs vary in structure and management, comparisons of data between health systems may be difficult. Registries and surveys provide data that are consistently collected and representative of broad populations but are limited in scope and may be updated only intermittently. RCT databases excel in the specificity, completeness, and accuracy of their data, but rarely include a fully representative sample of the general population. Also, they are costly to build and seldom maintained after a trial's end. To consider these issues, and the challenges and opportunities they present, the editors of Diabetes Care convened a group of experts in management of diabetes-related data on 21 June 2018, in conjunction with the American Diabetes Association's 78th Scientific Sessions in Orlando, FL. This article summarizes the discussion and conclusions of that forum, offering a vision of benefits that might be realized from prospectively designed and unified data-management systems to support the collective needs of clinical, surveillance, and research activities related to diabetes.

Real-world evidence concerning clinical and economic outcomes of switching to insulin glargine 300 units/mL vs other basal insulins in patients with type 2 diabetes using basal insulin.

This retrospective cohort study compared real-world clinical and healthcare-resource utilization (HCRU) data in patients with type 2 diabetes using basal insulin (BI) who switched to insulin glargine 300 units/mL (Gla-300) or another BI. Data from the Predictive Health Intelligence Environment database 12 months before (baseline) and 6 months after (follow-up) the switch date (index date, March 1, 2015 to May 31, 2016) included glycated haemoglobin A1c (HbA1c), hypoglycaemia, HCRU and associated costs. Baseline characteristics were balanced using propensity score matching. Change in HbA1c from baseline was similar in both matched cohorts (n = 1819 in each). Hypoglycaemia incidence and adjusted event rate were significantly lower with Gla-300. Patients switching to Gla-300 had a significantly lower incidence of HCRU related to hypoglycaemia. All-cause and diabetes-related hospitalization and emergency-department HCRU were also favourable for Gla-300. Lower HCRU translated to lower costs in patients using Gla-300. In this real-world study, switching to Gla-300 reduced the risk of hypoglycaemia in patients with type 2 diabetes when compared with those switching to another BI, resulting in less HCRU and potential savings of associated costs.

Fixed-dose combinations for treatment of type 2 diabetes mellitus.

INTRODUCTION: Combining antihyperglycemic agents with complementary mechanisms of action is a cornerstone of type 2 diabetes mellitus (T2DM) management. Although several fixed-dose combinations (FDCs) are available, representing standard types of combination therapy in T2DM, use of these products has been limited. METHODS: To address the likely concerns of prescribers and patients regarding the use of FDCs in the treatment of T2DM, literature searches were performed to ascertain the bioavailability, efficacy, tolerability, and cost-effectiveness of the currently approved FDCs compared with their individual component drugs given as separate pills in combination. Additionally, data were collected on rates of adherence, clinical outcomes, and overall treatment costs with FDCs versus dual therapy with the same constituent drugs. RESULTS: Bioavailability is equivalent for FDCs and dual therapy used in T2DM. Efficacy and tolerability also appear to be at least as good with FDCs as with dual therapy. Retrospective analyses have suggested that FDCs can enhance adherence to therapy, presumably as a result of the reduction in pill burden, and improved adherence may result in improved glycemic control and reduced disease management costs. In addition, because currently available FDCs come in two or more dose-strength formulations, they also afford some measure of dosing flexibility. CONCLUSIONS: The available evidence supports the wider use of FDCs in the treatment of patients with T2DM.

A simulation of the comparative long-term effectiveness of liraglutide and glimepiride monotherapies in patients with type 2 diabetes mellitus.

STUDY OBJECTIVE: To project and compare long-term outcomes of morbidity and mortality, and costs of complications of type 2 diabetes mellitus from a randomized controlled trial of patients receiving liraglutide versus glimepiride monotherapy. DESIGN: Mathematic simulation using the validated Center for Outcomes Research (CORE) Diabetes Model, calibrated to baseline patient characteristics from a short-term, randomized, controlled trial of liraglutide and glimepiride monotherapies (Liraglutide Effect and Action in Diabetes [LEAD]-3 trial) and using data from long-term outcomes studies. SETTING: Simulated routine clinical practice. PATIENTS: Seven hundred forty-six patients with type 2 diabetes who participated in the LEAD-3 trial, and three hypothetical cohorts of 5000 patients each that were based on the baseline characteristics of the patients in the LEAD-3 trial. The patients in the LEAD-3 trial were randomly assigned to monotherapy with liraglutide 1.2 mg/day (251 patients), liraglutide 1.8 mg/day (247 patients), or glimepiride 8 mg/day (248 patients). MEASUREMENTS AND MAIN RESULTS: The impact of the three treatments for type 2 diabetes on survival and cumulative incidence of cardiovascular, ocular, or renal events and costs were estimated at three time periods: 10, 20, and 30 years. Simulations predicted improved survival for liraglutide 1.8 and 1.2 mg at all three time points compared with glimepiride. Survival benefits were greatest after 30 years of follow-up: 16.5%, 13.6%, and 7.3%, respectively. The frequency of nonfatal renal and ocular events was lower for both liraglutide doses than for glimepiride. The rate of neuropathies leading to first or recurrent amputation was higher for glimepiride compared with both liraglutide doses. The average cumulative cost/patient was higher for glimepiride compared with liraglutide 1.2 mg and liraglutide 1.8 mg. CONCLUSION: With use of the CORE Diabetes Model and data from the LEAD-3 trial, long-term projected survival, diabetes complications, and costs favored liraglutide 1.2- and 1.8-mg monotherapies compared with glimepiride in the treatment of type 2 diabetes.

State of diabetes care in the United States.

As of 2005, it was estimated that 7% of the US population, approximately 21 million people, have diabetes. The major concern with diabetes is long-term complications, which are responsible for increased rates of morbidity and mortality. Studies have shown that lower glycosylated hemoglobin reduces the microvascular and macrovascular complications associated with diabetes. To achieve this goal, the American Diabetes Association provides treatment goals to aggressively control diabetes to improve outcomes and decrease morbidity and mortality. Although studies have proved the beneficial effects of currently used agents, there are still various concerns, including weight gain, high risk of hypoglycemia, poor postprandial control, and failure to maintain long-term glycemic control. With the advent of new incretin-related therapies, some of these concerns may be addressed. Diabetes is of growing concern, and better knowledge of treatment options and goals should be a priority for all healthcare professionals.

What are incretins, and how will they influence the management of type 2 diabetes?

OBJECTIVE: To review the pathophysiology of type 2 diabetes (T2DM), the role of incretins, the potential of incretin-based therapies to address unmet therapeutic needs in T2DM, and the potential impact this will have on the contribution of managed care pharmacy to diabetes therapy. SUMMARY: Diabetes, the fifth leading cause of death by disease in the United States, costs approximately $132 billion per year in direct and indirect medical expenses. According to the Centers for Disease Control and Prevention.s National Health and Nutrition Examination Survey, a majority of diabetes patients do not achieve target A1C levels with their current treatment regimens. Advances in understanding the pathophysiologic abnormalities underlying the metabolic dysfunctions associated with T2DM are leading to the development of new treatment approaches and new therapeutic classes of drugs. Novel incretin-based therapies currently available, and in late-stage development, are among those showing the greatest promise for addressing the unmet needs of traditional therapies.

Real-world trials to answer real-world questions.

Currently, there is a discrepancy between clinical trials designed to assess the efficacy and safety of a new medication under investigation and the real-life questions that need to be addressed regarding the clinical use of the medication by patients, healthcare professionals and society. The data necessary to obtain regulatory approval may be of limited relevance to policy makers when calculating economic parameters such as value for money or cost effectiveness. 'Real-world' studies examine questions relevant to health policy and reimbursement. There are many different forms of clinical trials, but in designing trials incorporating realistic budget impact estimates the important issue is to ensure we are asking a sensible question and attempting to answer it with an appropriate experimental design. As an example, a real-world trial currently underway that examines scenarios of introducing inhaled insulin into clinical practice is described.

Current challenges in diabetes management.

The burden of diabetes on the health care system mandates efforts to more optimally treat those with the disease and to prevent its development in those at risk. Early and intensive intervention in patients with diabetes reduces the risk of microvascular and macrovascular complications and disease progression. Current challenges in diabetes management include: (1) optimizing the use of currently available therapies to ensure adequate glycemic, blood pressure, and lipid control and to reduce complications; (2) educating patients on diabetes self-management; (3) improving patient adherence to lifestyle and pharmacologic interventions; (4) reducing barriers to the early use of insulin; and (5) improving the delivery of health care to people with chronic conditions.

New concepts in diabetes: how multihormonal regulation can improve glycemic control.

It is estimated that 18.2 million Americans are currently living with diabetes, a disease that continues to place significant economic burdens on patients, their families, health plans, systems, and society. Recent data from the American Diabetes Association indicates that the annual direct and indirect costs of diabetes are rapidly increasing. Improved glycemic control--which has been repeatedly demonstrated to reduce the risk of developing microvascular complications and is likely to reduce the risk of macrovascular complications associated with type 1 and type 2 diabetes--has the potential to improve quality of life and reduce health care expenditures. However, despite recent advances in oral antidiabetic agents and insulin management (e.g., development of rapid- and long-acting insulin analogs and continuous subcutaneous insulin infusion [CSII]), only a portion of the patient population is able to achieve the goals for glycemic control recommended by the American Diabetes Association, the American College of Endocrinology, and other guideline-setting organizations. Moreover, improved glycemia achieved with present therapeutic modalities may be associated with the risk of hypoglycemic events and undesired weight gain. The latter can negatively affect plasma lipids, blood pressure, and therapy adherence. New research into the pathophysiology of diabetes indicates that multiple hormones--not just insulin and glucagon but amylin, GLP-1 (a glucagon-like peptide), and others--are involved in the regulation of plasma glucose levels, providing insight into why even insulin is often ineffective in helping patient with diabetes achieve their glycemic goals. The use of analogs of these newly recognized, important glucoregulatory hormones; agents that delay the degradation of the hormones and therefore raise their concentration; and/or agents that bind to their receptors may facilitate achievement of improved glycemia. One of these agents, pramlintide, represents the first new potential antihyperglycemic agent for the treatment of type 1 diabetes since insulin was introduced more than 80 years ago. There is substantial potential for these agents to improve glycemic control and patient outcomes and to reduce the personal, societal, and economic burdens of diabetes. Some of these novel multihormonal glucoregulatory therapies will likely soon become important components of the diabetes armamentarium. It is therefore important that managed care pharmacy decision makers learn about them.

Thiazolidinediones in the treatment of managed care patients with type 2 diabetes.

Insulin resistance and progressive beta-cell failure are fundamental defects in type 2 diabetes. Treatments that improve insulin sensitivity and beta-cell function can improve these defects and improve glycemic control. The thiazolidinediones (TZDs) improve insulin sensitivity, fasting and postprandial plasma glucose levels, and glycosylated hemoglobin (HbA1c) levels. These agents can be used as monotherapy, and they have been successfully combined with other antidiabetic therapies. The TZDs have also been associated with improvements in various cardiovascular risk factors, including hypertension, the dyslipidemic profile often observed in patients with diabetes or insulin resistance, aspects of endothelial dysfunction, abnormal hemostasis, and levels of several inflammatory markers. Studies are currently under way to evaluate the effects of TZDs on cardiovascular event rates. Accumulating evidence suggests that TZDs may enhance or preserve beta-cell function and thus may have a more durable therapeutic effect than some of the other oral antidiabetic agents. Using TZDs as monotherapy or as a component of combination therapy will contribute to improved glycemic control and should reduce the risk of diabetic complications. A number of studies have shown that a strategy of aggressive use of pharmacologic agents to achieve glycemic control is associated with cost benefits.