Initiation and Titration of Basal Insulin in Primary Care: Barriers and Practical Solutions.

Basal insulin therapy is a critical part of effective type 2 diabetes (T2D) management for many patients, yet its initiation and titration are often delayed or avoided. Aversion to basal insulin therapy contributes to unnecessary hyperglycemia and poorer outcomes for patients. Primary care physicians often make decisions regarding the initiation of basal insulin in T2D, as they work closely with patients and are well placed to discuss and manage the transition to basal insulin therapy. However, many primary care clinicians hesitate to initiate basal insulin due to concerns regarding time or effort needed to educate patients, doubts about patient acceptance or ability to manage titration or injection, or patient fears of hypoglycemia. Resistance to basal insulin therapy is often linked to the outdated perception that the need for insulin represents a failure to control the disease, or that insulin is dangerous or toxic. Time concerns can be addressed via group classes and mobile technology and by working with diabetes educators in the community. Hypoglycemia or weight gain can be minimized with proper titration and use of second-generation basal insulins. This article reviews strategies for the initiation of basal insulin therapy, with an emphasis on the characteristics and titration of second-generation basal insulins, introducing current guidelines and offering suggestions for recognizing and overcoming barriers to insulin therapy in the management of T2D.

Primary Care Management of Patients With Type 2 Diabetes: Overcoming Inertia and Advancing Therapy With the Use of Injectables.

Type 2 diabetes (T2D) is a progressive disease caused by insulin resistance and associated progressive ß-cell functional decline, as well as multiple other related metabolic and pathophysiologic changes. Left unchecked, T2D increases the risk of long-term microvascular and cardiovascular complications and is associated with excess morbidity and mortality. Despite multiple effective options for reducing hyperglycemia, patients are not optimally managed, largely due to delays in appropriate and timely advancement of therapy. Glucagon-like peptide-1 receptor agonists and basal insulin are recommended by treatment guidelines as effective options for advancing therapy to achieve glycemic control. However, injected therapies often face resistance from patients and clinicians. Glucagon-like peptide-1 receptor agonists are associated with weight loss, low risk of hypoglycemia, and potential beneficial cardiovascular effects. The class is recommended for patients across the spectrum of disease severity and represents an attractive option to add to basal insulin therapy when additional control is needed. Newer second-generation basal insulin analogues offer advantages over first-generation basal insulins in terms of lower hypoglycemia rates and greater flexibility in dosing. Incorporating injectable therapy into patient care in a timely manner has the potential to improve outcomes and must not be overlooked. Primary care clinicians play a significant role in managing patients with T2D, and they must be able to address and overcome patient resistance and their own barriers to advancing therapy if optimal treatment outcomes are to be achieved. The purpose of this expert opinion article was to provide a commentary on the key principle of advancing therapy with injectables to control hyperglycemia.

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.

Fixed-ratio combination therapy for type 2 diabetes: the top ten things you should know about insulin and glucagon-like peptide-1 receptor agonist combinations.

Many individuals with type 2 diabetes (T2D) will eventually require insulin therapy to help achieve and maintain adequate glycemic control. However, the use of insulin can be associated with adverse effects such as hypoglycemia and weight gain, and in some patients the addition of insulin to treatment regimens is often still insufficient to achieve target glycemic control. Combining basal insulin with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) for the treatment of patients with T2D has been demonstrated to be effective and well tolerated, while mitigating many of the adverse events associated with giving either of these drug classes alone. Two titratable, fixed-ratio combination therapies, iGlarLixi and IDegLira, that combine basal insulin and a GLP-1 RA in a once-daily subcutaneous injection are currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with T2D. The fixed-ratio combination iGlarLixi combines insulin glargine 100 Units/mL with lixisenatide, while IDegLira combines insulin degludec 100 Units/mL with liraglutide. While these new fixed-ratio combinations contain antihyperglycemic medications that are familiar to most health care providers, there are many questions relating to their use when formulated as a fixed-ratio combination therapy. This article discusses the 'top 10' considerations that health care providers should know about these novel combination therapies as these agents begin to gain an increasing presence in clinical practice.

Making Insulin Accessible: Does Inhaled Insulin Fill an Unmet Need?

UNLABELLED: Glycemic control is fundamental to the management of diabetes. However, studies suggest that a significant proportion of people with diabetes, particularly those using insulin, are not achieving glycemic targets. The reasons for this are likely to be multifactorial. The real and perceived risk of hypoglycemia and the need for multiple daily injections are widely recognized as key barriers to effective insulin therapy. Therefore, there is a clear unmet need for a treatment option which can help mitigate these barriers. Alternative methods of insulin administration have been under investigation for several years, and pulmonary delivery has shown the most promise to date. Inhaled Technosphere(®) Insulin (TI; Afrezza(®); MannKind Corporation) was approved in 2014 for use as prandial insulin in people with diabetes. TI shows a more rapid onset of action and a significantly faster decline in activity than current subcutaneous rapid-acting insulin analogs (RAAs), and TI is more synchronized to the physiologic timing of the postprandial glucose excursion. This results in lower postprandial hypoglycemia with similar glycemic control compared with RAAs, and less weight gain. Together with the ease of use of the TI inhaler and the reduction in the number of daily injections, these findings imply that TI may be useful in helping to overcome patient resistance to insulin, improve adherence and mitigate clinical inertia in health-care providers, with potential beneficial effects on glycemic control. FUNDING: Writing and editorial support in the preparation of this publication was funded by Sanofi US, Inc., Bridgewater, New Jersey, USA. Funding for the article processing charges for this publication was provided by MannKind Corporation.

The past, present, and future of basal insulins.

Insulin production by the pancreas follows a basic pattern where basal levels of insulin are secreted during fasting periods, with prandial increases in insulin associated with food ingestion. The aim of insulin therapy in patients with diabetes is to match the endogenous pattern of insulin secretion as closely as possible without causing hypoglycaemia. There are several optimal pharmacokinetic and pharmacodynamic properties of long-acting basal insulins that can help to achieve this aim, namely, as follows: activity that is flat and as free of peaks as possible, a duration of action of ≥24-h, and as little day-to-day variation as possible. The long-acting basal insulins are a fundamental therapy for patients with type 1 and type 2 diabetes, and those that are currently available have many benefits; however, the development of even longer-acting insulins and improved insulin delivery techniques may lead to better glycemic control for patients in the future. Established long-acting basal insulins available in the United States and Europe include insulin glargine 100 units/mL and insulin detemir, both of which exhibit similar glycemic control to that of the intermediate-acting neutral protamine Hagedorn insulin, but with a reduction in hypoglycaemia. Newer insulin products available include new insulin glargine 300 units/mL (United States and Europe) and the ultra-long-acting insulin degludec (Europe) with basal insulin peglispro currently in development. These new insulins demonstrate different pharmacokinetic/pharmacodynamic profiles and longer durations of action (>24 h) compared with insulin glargine 100 units/mL, which may lead to potential benefits. The introduction of biosimilar insulins may also broaden access to insulins by reducing treatment costs. Copyright © 2015 John Wiley & Sons, Ltd.

Inhaled insulin: a breath of fresh air? A review of inhaled insulin.

PURPOSE: Despite many advances in diabetes care over the last century, some elements of insulin therapy remain inadequate for optimal care of the patient with diabetes. There is a need for improved pharmacokinetics and pharmacodynamics of rapid-acting insulin analogues to mimic physiologic insulin secretion. In addition, a major barrier to successful insulin therapy has been patient resistance. Alternative routes of insulin administration, including inhaled insulin, have been under investigation for several years. This review discusses the rationale for pulmonary delivery of insulin, compares previous inhaled insulin products, reviews the literature on the safety and efficacy of a current inhaled insulin formulation under investigation, and compares this product with other prandial insulin products. METHODS: English-language studies and reviews of inhaled insulin were searched in MEDLINE, the ClinicalTrials.gov registry (through May 2014), and the US Food and Drug Administration Website. FINDINGS: Inhaled insulin has several favorable characteristics due to pulmonary anatomy/physiology and the lack of injections. Pharmacokinetic and pharmacodynamic studies have shown a time-action profile suitable for prandial insulin use. Inhaled insulin seems to be safe and effective compared with other prandial insulin products and may be preferable to subcutaneous rapid-acting insulin analogues in terms of time-action profiles and rates of hypoglycemia. Small decreases in forced expiratory volume in 1 second (FEV1) have been shown with inhaled insulin, although this finding is not progressive over time and reverses with cessation of the medication. IMPLICATIONS: Although several inhaled insulin products have been under investigation, only one (Exubera(®) [Nektar Therapeutics, San Carlos, California/Pfizer Inc, New York, New York]) was approved by the US Food and Drug Administration, and it was pulled from the market after only a short period of time. Technosphere(®) insulin (MannKind Corporation, Valencia, California) is currently the only inhaled insulin that remains under investigation. A review of the past and present literature on inhaled insulin is pertinent in understanding the current status of inhaled insulin and its risks and benefits. The current literature suggests that inhaled insulin could be a valuable option for prandial insulin administration, with a favorable risk to benefit ratio in some patients.