Shifting Paradigms in the Medical Management of Type 2 Diabetes: Reflections on Recent Cardiovascular Outcome Trials.

An important challenge in the management of patients with type 2 diabetes is cardiovascular disease (CVD) prevention. While it is well established that intensive glycemic control prevents the onset and slows the progression of certain microvascular complications, such a strategy utilized in multiple clinical trials over the past few decades has failed to show a similar benefit with regard to cardiovascular events, including mortality. Despite this, a major hope has been the discovery of glucose-lowering medications that simultaneously improve cardiovascular outcomes. Over the past year and a half, four randomized clinical trials (involving empagliflozin, pioglitazone, liraglutide, and semaglutide) have reported important benefits in preventing adverse cardiovascular outcomes in patients with or at risk for type 2 diabetes and established CVD. On the basis of these landmark trials, we propose that a paradigm shift in the management of patients with type 2 diabetes, specifically in those with prior macrovascular disease. A transition from current algorithms based primarily on hemoglobin A1c values to a more comprehensive strategy additionally focused on CVD prevention seems warranted.

Hyperglycemia grand rounds: descriptive findings of outcomes from a continuing education intervention to improve glycemic control and prevent hypoglycemia in the hospital setting.

UNLABELLED: Hyperglycemia is common in the hospital in-patient setting and is associated with adverse outcomes. Healthcare professionals (HCPs) often fail to use best practices established to manage this condition or to coordinate care among team members. OBJECTIVES: The objective of the Hyperglycemia Grand Rounds (HGR) continuing education initiative was to improve knowledge levels in a team setting, leading to improved clinical competence, evidence-based behaviors, and improved patient care. METHODS: To achieve that goal, a four-module seminar series was presented to HCPs on-site in a "Grand Rounds" format at healthcare institutions across the United States. Outcomes data included satisfaction, learning, impact, and intent-to-implement measures at event time and at follow-up. At the site level, detailed questionnaires assessed skill gaps and expected outcomes from administrators at the time the modules were scheduled and the impact after modules were completed. Demographic information allowed identification of HCPs receiving maximum benefits; data on barriers to implementation are reported. RESULTS: Seventy-eight percent of participants self-reported a positive impact on competence, performance, or patient outcomes. Forty percent of learners said they intended to make specific changes in practices. Eighty-two percent of administrators confirmed expected changes in their health system. The follow-up study concurred with the initial findings. CONCLUSION: The HGR was an effective program in improving self-reported competence amongst attendees that could potentially lead to improved care. This descriptive report summarizes outcomes from 1 year of educational efforts to more than 2000 healthcare professionals.

Individualizing insulin therapy in the management of type 2 diabetes.

It is recognized that reducing hyperglycemia early on in disease progression has long-term benefits for patients with diabetes. Insulin therapy has greater potential to reduce hyperglycemia than other therapies; however, there is often a significant delay in insulin initiation and intensification. Insulin replacement therapy in type 2 diabetes should no longer be viewed as the treatment of last resort. With the development of modern insulin analogs, the field has evolved. Large clinical trials have improved our understanding of the potential benefits and risks associated with intensive glycemic control in different patient populations and highlighted the need for individualization of glycemic targets and treatment strategies. Current treatment guidelines recognize the important role of insulin therapy both early on and throughout the progression of type 2 diabetes.

Treating patients with diabetes of long duration: GLP-1 receptor agonists and insulin in combination.

Patients with long-standing type 2 diabetes mellitus (T2DM) can be clinically challenging for physicians to treat because these patients often lack sufficient ß-cell function to respond to some oral glucose-lowering agents, may have profound comorbidities, and may have renal impairment that limits the use of traditional agents. These complications, in addition to older age, also increase the risk of hypoglycemia, which can be a major barrier to treatment success. Individualizing treatment targets to balance the benefits of glycemic control with risks of hypoglycemia is the first step to successfully treating these patients. Careful selection of combination therapy strategies to address limited ß-cell function, renal function, and cardiovascular status, along with attention to selection of agents associated with lower risk of hypoglycemia, is important. Basal insulin analogs are often used in patients with long-standing diabetes to address insulinopenic states. Incretin-based therapies, particularly GLP-1 receptor agonists, provide postprandial control with lower risks of hypoglycemia than prandial insulin. The author discusses the management of patients with long-standing diabetes who may have limited ß-cell function and require transition to insulin therapy with gradual intensification.

Management of type 2 diabetes mellitus in older patients: current and emerging treatment options.

Elderly patients with type 2 diabetes mellitus (T2DM) are a rapidly emerging population that presents unique clinical challenges. This diverse patient group can differ widely in terms of physical and mental status, which can increase their risk of complications including hypoglycemia, falls, and depression. These factors can negatively impact their glycemic control, safety, and quality of life. The risk of hypoglycemic events is elevated among elderly patients with diabetes. In many cases, these events are related to antidiabetic therapy and the pursuit of strict glycemic control. Fear of a hypoglycemic episode, on the part of the patient and/or healthcare provider, is another major barrier to achieving glycemic control. Hypoglycemic events, even in the absence of awareness of the event (asymptomatic), can have negative consequences. To help manage these risks, several national and international organizations have proposed guidelines to address individualized treatment goals for older adults with diabetes. This article reviews current treatment guidelines for setting glycemic targets in elderly patients with T2DM, and discusses the role of emerging treatment options in this patient population.

Hypoglycemia: minimizing its impact in type 2 diabetes.

OBJECTIVE: To review and discuss the risks and impact of hypoglycemia and provide guidance for the prevention of hypoglycemia in type 2 diabetes (T2DM). METHODS: We review and discuss the risks and impact of hypoglycemia, providing specific guidance regarding the prevention of hypoglycemia and judicial selection of glucose-lowering agents in individuals with T2DM. RESULTS: Hypoglycemia in T2DM is underrecognized and underreported. Emerging evidence from large clinical trials suggest that hypoglycemia may be an important risk factor for morbidity and mortality in T2DM. In addition, hypoglycemia is associated with reduced quality of life, greater healthcare utilization costs, and poor adherence to medical regiments. CONCLUSION: These findings have led professional organizations to emphasize the prevention of hypoglycemia as an important consideration when initiating or intensifying treatment regimens. In clinical settings, particular attention should be paid to a patient's risk for hypoglycemia when initiating or intensifying the pharmacological treatment regimen. The endocrinologist can play an important role in educating not only the patient, but also other members of the diabetes-management team regarding the need for individualized therapy.

Diversity in diabetes: the role of insulin aspart.

Diabetes management is changing not only with novel treatments but also in patient demography. This presents clinical challenges and influences our view of diabetes therapies. Insulin analogues have been developed to overcome some of the limitations of traditional human insulins, with the aim of providing a more physiological pharmacokinetic/pharmacodynamic profile. The rapid-acting insulin analogue insulin aspart has been investigated in many clinical trials over the past 10 years and the aim of this review is to present the insulin aspart clinical trial data from across the spectrum of patients with diabetes. Five studies have looked at insulin aspart use (including continuous subcutaneous insulin infusion) in children and adolescents, where the analogue was as effective and well tolerated as soluble human insulin. One large-scale, randomized, controlled trial in pregnant women with type 1 diabetes observed trends towards a reduction in major hypoglycaemia, fewer preterm deliveries and lower birthweight with insulin aspart compared with soluble human insulin. Two 6-month, randomized, controlled, multicentre, multinational, parallel-group, open-label trials reported significant reductions in haemoglobin A(1c) and major nocturnal hypoglycaemia with insulin aspart compared with soluble human insulins in patients with type 1 diabetes. There are fewer data involving insulin analogue use in hospitals and in elderly patients with diabetes, but some recent studies have investigated insulin aspart in the emergency department, intensive/non-intensive care setting and in a pharmacokinetic/pharmacodynamic study in patients aged ≥ 65 years. In summary, the evidence would suggest that insulin aspart is suitable for use in a variety of patients with diabetes.

A look into the future: improving diabetes care by 2015.

Insulin initiation, which was traditionally the province of specialists, is increasingly undertaken by primary care. However, significant barriers to appropriate and timely initiation still exist. Whilst insulin is recognized as providing the most effective treatment in type 2 diabetes, it is also widely considered to be the most challenging and time consuming. This editorial identifies that the organization of existing healthcare services, the challenges faced by patients, and the treatments themselves contribute to suboptimal insulin management. In order to improve future diabetes care, it will be necessary to address all three problem areas: (1) re-think the best use of existing human and financial resources to promote and support patient self-management and adherence to treatment; (2) empower patients to participate more actively in treatment decision making; and (3) improve acceptance, persistence and adherence to therapy by continuing to refine insulin therapy and treatment regimens in terms of safety, simplicity and convenience. The principles discussed are also applicable to the successful management of any chronic medical illness.

Individualizing glycemic targets in type 2 diabetes mellitus: implications of recent clinical trials.

One of the first steps in the management of patients with type 2 diabetes mellitus is setting glycemic goals. Professional organizations advise setting specific hemoglobin A(1c) (HbA(1c)) targets for patients, and individualization of these goals has more recently been emphasized. However, the operational meaning of glycemic goals, and specific methods for individualizing them, have not been well-described. Choosing a specific HbA(1c) target range for a given patient requires taking several factors into consideration, including an assessment of the patient's risk for hyperglycemia-related complications versus the risks of therapy, all in the context of the overall clinical setting. Comorbid conditions, psychological status, capacity for self-care, economic considerations, and family and social support systems also play a key role in the intensity of therapy. The individualization of HbA(1c) targets has gained more traction after recent clinical trials in older patients with established type 2 diabetes mellitus failed to show a benefit from intensive glucose-lowering therapy on cardiovascular disease (CVD) outcomes. The limited available evidence suggests that near-normal glycemic targets should be the standard for younger patients with relatively recent onset of type 2 diabetes mellitus and little or no micro- or macrovascular complications, with the aim of preventing complications over the many years of life. However, somewhat higher targets should be considered for older patients with long-standing type 2 diabetes mellitus and evidence of CVD (or multiple CVD risk factors). This review explores these issues further and proposes a framework for considering an appropriate and safe HbA(1c) target range for each patient.

Reexamining the evidence for inpatient glucose control: new recommendations for glycemic targets.

PURPOSE: To review the risks of hyperglycemia in hospitalized patients, data supporting the benefits of treating hyperglycemia, and recommendations from the 2009 American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on the management of inpatient hyperglycemia. SUMMARY: Inpatient hyperglycemia is common, costly, and associated with poor clinical outcomes in many disease states. Despite inconsistencies in clinical trial results, good glucose management in the hospital remains important. Target blood glucose concentrations (BGs) were recently modified to somewhat higher values with the expectation that the benefit of treatment will persist with a lower risk of hypoglycemia, which is itself another marker of poor outcome in critically and non-critically ill patients. In the intensive care unit (ICU), the threshold to start treatment is a BG of 180 mg/dL are no longer recommended. In non-critically ill patients, premeal BG targets are <140 mg/dL; random BGs of <180 mg/dL are recommended. Scheduled subcutaneous insulin is the treatment of choice for hyperglycemia in non-critically ill patients; use of sliding-scale insulin is strongly discouraged. To avoid hypoglycemia, insulin regimens should be reassessed if BG falls to <100 mg/dL. CONCLUSION: Poor glycemic control in the hospital setting is a quality-of-care, safety, and cost issue. Safe and effective strategies to implement optimal glycemic control require multidisciplinary involvement. Insulin given i.v. in the ICU or subcutaneously on an as-scheduled regimen in other parts of the hospital is the treatment of choice.

Addressing hyperglycemia from hospital admission to discharge.

BACKGROUND: This review examines glycemia management practices in hospitalized patients. Optimal glycemic control remains a challenge among hospitalized patients. Recent studies have questioned the benefit of tight glycemic control and have raised concerns regarding the safety of this approach. As a result, medical societies have updated glycemic targets and have published new consensus guidelines for management of glycemia in hospitalized patients. This review highlights recent inpatient glycemic trials, the new glycemic targets and recommended strategies for management of glycemia in hospitalized patients. METHODS: Medline and PubMed searches (diabetes, hyperglycemia, hypoglycemia, intensive therapy insulin, tight glycemic control, and hospital patients) were performed for English-language articles on treatment of diabetes, insulin therapy, hyperglycemia or hypoglycemia in hospitalized patients published from 2004 to present. Earlier works cited in these papers were surveyed. Clinical studies, reviews, consensus/guidelines statements, and meta-analyses relevant to the identification and management of diabetes and hyperglycemia in hospitalized patients were included and selected. This is not an exhaustive review of the published literature. RESULTS: Insulin remains the most appropriate agent for a majority of hospitalized patients. In critically ill patients insulin is given as a continuous intravenous (IV) infusion and in non-critically ill inpatients hyperglycemia is best managed using scheduled subcutaneous (SC) basal-bolus insulin regimens supplemented with correction doses as needed and adjusted daily with the guidance of frequent blood glucose monitoring. Prevention of hypoglycemia is equally as important to patient outcomes and is an equally necessary part of any effective glucose control program. Modern insulin analogs offer advantages over the older human insulins (e.g., regular and neutral protamine Hagedorn [NPH] insulin) because their time-action profiles more closely correspond to physiological basal and prandial insulin requirements, and have a lower propensity for inducing hypoglycemia than human insulin formulations. Long-acting basal insulin analogs (glargine, detemir) are suitable and preferred for the basal component of therapy; rapid-acting insulin analogs (aspart, lispro, glulisine) are recommended for bolus and correction doses. Sliding-scale insulin (SSI) regimens are not effective and should not be used, especially as this excludes a basal insulin component from the therapy. CONCLUSIONS: Optimal glycemic management in the hospital setting requires judicious treatment of hyperglycemia while avoiding hypoglycemia. Insulin is the most appropriate agent for management of hyperglycemia for the majority of hospitalized patients. Intravenous insulin infusion is still preferred during and immediately after surgery, but s.c. basal insulin analogs with prandial or correction doses should be used after the immediate post-operative period, and also should be used in non-critically ill patients. Frequent and effective glucose monitoring is critical for avoiding wide deviations from acceptable glucose levels, which under a recently promulgated consensus guideline currently range between 140 mg/dL and 180 mg/dL. Glucose targets near 140 mg/dL are recommended as being the most appropriate for all hospitalized patients.

Comparisons of different insulin infusion protocols: a review of recent literature.

PURPOSE OF REVIEW: To provide an update on the currently available insulin infusion protocols for treatment of hyperglycemia in critically ill patients and to discuss the major differences and similarities among them. RECENT FINDINGS: We identified a total of 26 protocols, 20 of which used manual blood-glucose calculations, and six that used computerized algorithms. The major differences and similarities among the insulin infusion protocols were in the following areas: patient characteristics, target glucose level, time to achieve target glucose level, incidence of hypoglycemia, rationale for adjusting the rates of insulin infusion, and methods of blood-glucose measurements. Several computerized protocols hold promise for safer achievement of glycemic targets. SUMMARY: Insulin infusion is the most effective method for controlling hyperglycemia in critically ill patients. Clinicians should utilize a validated insulin infusion protocol that is well tolerated, and is most appropriate and practical for their institution based on the resources that are available.

Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control.

This report presents an algorithm to assist primary care physicians, endocrinologists, and others in the management of adult, nonpregnant patients with type 2 diabetes mellitus. In order to minimize the risk of diabetes-related complications, the goal of therapy is to achieve a hemoglobin A1c (A1C) of 6.5% or less, with recognition of the need for individualization to minimize the risks of hypoglycemia. We provide therapeutic pathways stratified on the basis of current levels of A1C, whether the patient is receiving treatment or is drug naïve. We consider monotherapy, dual therapy, and triple therapy, including 8 major classes of medications (biguanides, dipeptidyl-peptidase-4 inhibitors, incretin mimetics, thiazolidinediones, alpha-glucosidase inhibitors, sulfonylureas, meglitinides, and bile acid sequestrants) and insulin therapy (basal, premixed, and multiple daily injections), with or without orally administered medications. We prioritize choices of medications according to safety, risk of hypoglycemia, efficacy, simplicity, anticipated degree of patient adherence, and cost of medications. We recommend only combinations of medications approved by the US Food and Drug Administration that provide complementary mechanisms of action. It is essential to monitor therapy with A1C and self-monitoring of blood glucose and to adjust or advance therapy frequently (every 2 to 3 months) if the appropriate goal for each patient has not been achieved. We provide a flow-chart and table summarizing the major considerations. This algorithm represents a consensus of 14 highly experienced clinicians, clinical researchers, practitioners, and academicians and is based on the American Association of Clinical Endocrinologists/American College of Endocrinology Diabetes Guidelines and the recent medical literature.