iGlarLixi: A New Once-Daily Fixed-Ratio Combination of Basal Insulin Glargine and Lixisenatide for the Management of Type 2 Diabetes.

BACKGROUND: Patients with type 2 diabetes require treatment intensification to maintain glycemic control. Clinician reluctance, patient injection fears, hypoglycemia, weight gain, or other objections may lead to clinical inertia, whereby therapy is not intensified and patients live with uncontrolled hyperglycemia and increased risk for complications. Initiation of injectable therapy with a glucagon-like peptide (GLP)-1 receptor agonist and/or basal insulin is a recommended option for patients with type 2 diabetes inadequately controlled on one or more oral agents. PURPOSE: This article reviews clinical evidence and provides information on dosing and administration of iGlarLixi, a titratable fixed-ratio combination of insulin glargine and the GLP-1 receptor agonist lixisenatide that effectively lowers both fasting and postprandial glucose levels. FINDINGS: In phase 3 trials, iGlarLixi provided greater A1C reduction than insulin glargine or lixisenatide alone, without increased hypoglycemia risk compared with insulin glargine. iGlarLixi did not lead to weight gain versus insulin glargine and was associated with a lower frequency of gastrointestinal adverse effects than lixisenatide. iGlarLixi was recently approved by the U.S. Food and Drug Administration to improve glycemic control in adults with type 2 diabetes inadequately controlled on basal insulin (<60 units daily) or lixisenatide. iGlarLixi is administered by subcutaneous injection once daily, and the dose is titrated based on each patient's insulin needs using a simple titration algorithm. CONCLUSION: iGlarLixi offers an effective and well-tolerated treatment option for patients with type 2 diabetes requiring additional glycemic control, with comparable or improved safety outcomes than its separate components. Because of its simple regimen and low rate of adverse effects, iGlarLixi may improve adherence and, consequently, therapeutic outcomes.

Initiating Titratable Fixed-Ratio Combinations of Basal Insulin Analogs and Glucagon-Like Peptide-1 Receptor Agonists: What You Need to Know.

IN BRIEF Titratable fixed-ratio combinations (FRCs) of a basal insulin and a glucagon-like peptide-1 (GLP-1) receptor agonist are new therapeutic options for people with type 2 diabetes. Two FRCs-insulin degludec/liraglutide and insulin glargine/lixisenatide-have been approved for use in the United States. The two components in these FRCs target different aspects of diabetes pathophysiology, working in a complementary manner to decrease blood glucose while mitigating the side effects associated with each component (hypoglycemia and weight gain with insulin and gastrointestinal side effects with GLP-1 receptor agonists). This article reviews these products and key considerations for their use.

How Similar Are Biosimilars? What Do Clinicians Need to Know About Biosimilar and Follow-On Insulins?

IN BRIEF As more patents on biological medicines expire, increased numbers of biologic copies, referred to as "biosimilars," will likely become available in the United States in the coming years. With greater availability and the drive for health care savings, the use of biosimilars and of "follow-on" biological products is likely to increase in routine clinical practice. Health care practitioners need to be fully aware of these products and accompanying considerations if they are to make informed decisions together with their patients.

Therapeutic Options for the Management of Postprandial Glucose in Patients With Type 2 Diabetes on Basal Insulin.

In Brief For patients with type 2 diabetes who require add-on therapy to metformin plus basal insulin, GLP-1 receptor agonists may be a favorable option because they effectively manage postprandial glucose, reduce body weight, and have an overall favorable safety profile compared to other agents. Given the wide range of treatment combinations available for type 2 diabetes management, health professionals must partner with patients to determine the best choices based on patients' individual lifestyle, resources, and treatment goals.

The role of the kidney in hyperglycemia: a new therapeutic target in type 2 diabetes mellitus.

BACKGROUND: Diabetes is a complex and chronic metabolic disease characterized by hyperglycemia due to defects in the secretion and action of insulin. Diabetes affects more than 8% of the US population. Type 2 diabetes mellitus (T2DM) is the most common form of diabetes and is associated with the development of a number of devastating microvascular complications, including retinopathy, neuropathy, and nephropathy. Diabetes is also a major risk factor for heart disease and stroke. Despite the availability of numerous treatment options for T2DM, glycemic control rates remain poor. Recently, there has been renewed interest in the role that the kidney plays in glucose homeostasis and the potential of the kidney as a therapeutic target in T2DM. PURPOSE: This article discusses the role of the kidneys and particularly sodium glucose cotransporter 2 in glucose homeostasis and the potential of inhibiting this transporter as a new treatment option for T2DM. CONCLUSIONS: The kidney plays an important role in glucose homeostasis by reabsorbing filtered glucose. In patients with T2DM, glucose reabsorption appears to be increased, potentially contributing to the hyperglycemia associated with this disease. Initial results from clinical trials with a number of sodium glucose cotransporter 2 inhibitors suggest that these compounds act to increase glucose excretion and decrease plasma glucose and body weight, and are generally well tolerated and do not appear to increase the risk of hypoglycemia. CLINICAL IMPLICATIONS: Sodium glucose cotransporter 2 inhibitors have a unique mechanism of action that is independent of insulin secretion or action. Results from ongoing and future clinical trials will determine whether this class of compounds becomes a treatment option for reducing hyperglycemia in patients with T2DM.

Type 2 diabetes and cardiovascular disease: risk reduction and early intervention.

People with type 2 diabetes (T2D) have a higher risk of cardiovascular (CV) disease (CVD) than those without. This increased risk begins with pre-diabetes, potentially 7-10 years before T2D is diagnosed. Selecting medication for patients with T2D should focus on reducing the risk of CVD and established CVD. Within the last decade, several antihyperglycemic agents with proven CV benefit have been approved for the treatment of hyperglycemia and for the prevention of primary and secondary CV events, including glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors. T2D treatment guidelines recommend that an antihyperglycemic agent with proven CV benefit should be used after metformin in patients with high risk of or established CVD, regardless of glycated hemoglobin levels. Despite the availability of antihyperglycemic agents with proven CV benefit, and guidelines on when to use them, less than one in four patients with T2D and CVD receive this type of therapy. These findings suggest a potential gap between current recommendations and clinical practice. This article reviews the approved agents with CV indications, with a focus on injectable GLP-1RAs, and their place in the T2D treatment paradigm according to current guidelines. We aim to provide primary healthcare providers with in-depth information on subsets of patients who would benefit from this type of therapy and when it should be initiated, taking into consideration safety and tolerability and other disease factors. An individualized treatment approach is increasingly recommended in the management of T2D, employing a shared decision-making strategy between patients and healthcare professionals.

GLP-1 receptor agonists and cardiovascular outcomes in patients with type 2 diabetes: Clinical evidence and best practice.

ABSTRACT: Cardiovascular disease (CVD) is a major cause of death and disability among people with type 2 diabetes (T2D), presenting a significant impact on longevity, patient quality of life, and health care costs. In the United States, attainment of recommended glycemic targets is low and T2D-related cardiovascular complications remain a significant burden. Many glucose-lowering treatment options are available, but glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are recommended in recent guidelines as the preferred add-on therapy to metformin to improve glycemic control. This is particularly the case for patients with T2D and established atherosclerotic CVD, at high risk of atherosclerotic CVD, and/or with chronic kidney disease. Recommendations were based on GLP-1RA and SGLT-2 inhibitor cardiovascular outcomes trials (CVOTs), which consistently showed that these agents pose no additional cardiovascular risk compared with placebo. Three GLP-1RAs (liraglutide, dulaglutide, and subcutaneous semaglutide) demonstrated significantly lower major adverse cardiovascular events versus placebo and are now approved for this indication. However, to realize improvement in outcomes in the clinical setting, organized, systematic, and coordinated approaches to patient management are also needed. For example, nurse-led diabetes self-management education and support programs have been shown to be effective. This article explores T2D management with emphasis on cardiovascular risk and CVOTs performed to date and reviews the clinical experience with GLP-1RAs for managing hyperglycemia and their impact on cardiovascular risk. In addition, practical guidance is given for key health care providers involved in the care of patients with T2D with cardiovascular risk outside of diabetes clinics/endocrinology centers.

Target attainment in insulin-naive patients at high risk for hypoglycemia: Results from ACHIEVE Control.

AIMS: To better understand outcomes in people with type 2 diabetes at high risk of hypoglycemia, we conducted post hoc analyses in subgroups of participants from the real-world ACHIEVE Control study (NCT02451137) with ≥1 hypoglycemia risk factor. METHODS: Insulin-naive adults with type 2 diabetes and A1c ≥8% were randomized 1:1 to insulin glargine 300 U/mL (Gla-300) or standard-of-care basal insulin (SOC-BI). Participants had documented history of ≥1 risk factors for hypoglycemia: chronic kidney disease, cardiovascular disease, dementia or blindness, age ≥65 years, or history of hypoglycemia. Outcomes included individualized A1c target attainment without documented symptomatic hypoglycemia (blood glucose [BG] ≤3.9 mmol/L or <3.0 mmol/L) or severe hypoglycemia, A1c target attainment, and absence of documented symptomatic or severe hypoglycemia at 6 and 12 months. RESULTS: Within subgroups, odds ratios generally showed trends favoring Gla-300 versus SOC-BI, particularly for hypoglycemia avoidance in participants ≥65 years of age (BG ≤3.9 mmol/L; odds ratio, 1.52; 95% confidence interval, 1.14-2.03) and those with chronic kidney disease (BG ≤3.9 mmol/L; odds ratio, 2.28; 95% confidence interval, 1.26-4.12). Results were consistent with the overall population. CONCLUSIONS: These data suggest potential benefit of Gla-300 versus SOC-BI for avoiding hypoglycemia in participants with ≥1 hypoglycemia risk factor.

Hypoglycemia and diabetes: increased need for awareness.

Hypoglycemia is an abnormally low plasma glucose concentration that may expose individuals to potential harm. It is associated with treatment of type 1 diabetes and type 2 diabetes. Diabetes-related hypoglycemia may result in various complications, reduced quality of life, and increased costs. Hypoglycemia, therefore, impacts patient management and must be considered by primary healthcare practitioners at the forefront of diabetes care. This paper reviews the impact of hypoglycemia on patients and healthcare practitioners in the clinical setting. Recognizing hypoglycemia and its risk factors and identifying high-risk patients can assist with prevention and management. Prevention rather than treatment of hypoglycemia is preferable by individualizing glycemic goals, considering hypoglycemia risk factors, and continuing professional support. Education of patients and healthcare practitioners is also a key factor in hypoglycemia prevention. Although several newer-generation therapies and treatment strategies for type 2 diabetes have a lower risk of hypoglycemia than established agents, long-term safety data are currently lacking. Thus, choice of therapy is important, with hypoglycemic risk varying according to drug selection.

Putting medications where they belong: practical advice for managing type 2 diabetes in clinical practice.

PURPOSE: Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder that affects almost 24 million Americans. Healthcare providers often do not initiate and/or intensify therapy appropriately during patient visits, which may be due, in part, to a lack of understanding of the new diabetes medications. This review focuses on means by which primary care nurse practitioners (NPs) might evaluate the utility of pharmacologic agents based upon their relation to the pathogenesis of T2DM. DATA SOURCES: The evidence used in developing this review included evidence-based reviews, clinical trials, cohort studies, position statements, and guidelines. The authors obtained relevant reports through a computerized search of the literature using PubMed, MEDLINE, and other search engines and scanning syllabi from national and international meetings on the subject of type 2 diabetes. CONCLUSIONS: Medications used to manage T2DM utilize different pharmacologic approaches. These include stimulating insulin production, reducing hepatic gluconeogenesis, slowing polysaccharide digestion, and increasing insulin sensitivity in muscle, liver, and fat to achieve euglycemia. IMPLICATIONS FOR PRACTICE: Patients with T2DM should be treated to their lowest targeted glycemic goals as soon as they are diagnosed as safely and as rationally as possible. NPs in primary care practice can facilitate more effective diabetes management.