Efficacy of iGlarLixi in adults with type 2 diabetes inadequately controlled (glycated haemoglobin ≥8%, ≥64 mmol/mol) on two oral antidiabetes drugs: Post hoc analysis of the LixiLan-O randomized trial.

AIMS: To assess the efficacy and safety of iGlarLixi (the titratable fixed-ratio combination of insulin glargine 100 U/mL [iGlar] plus lixisenatide [Lixi]), in adults with type 2 diabetes (T2D) with glycated haemoglobin (HbA1c) levels ≥8% (≥64 mmol/mol). MATERIALS AND METHODS: The LixiLan-O study (NCT02058147) compared iGlarLixi with iGlar or Lixi in adults with T2D inadequately controlled on metformin ± a second oral antidiabetes drug (OAD). This exploratory analysis evaluated the LixiLan-O subgroup of participants with baseline HbA1c levels of ≥8% (≥64 mmol/mol) who were receiving metformin plus a second OAD at screening. RESULTS: The mean diabetes duration was 10.0 years, and the mean duration of second OAD use was 4.5 years. iGlarLixi demonstrated greater mean reductions from baseline in HbA1c and 2-hour postprandial glucose (PPG) compared with iGlar or Lixi (HbA1c -1.9% vs. -1.6% or -1.0% [-20 vs. -17 or -10 mmol/mol; 2-hour PPG -7.2 vs. -4.6 or -5.5 mmol/L). Greater proportions of participants achieved HbA1c <7% (<53 mmol/mol) with iGlarLixi versus iGlar or Lixi (67% vs. 51% or 18%), and the composite endpoints of HbA1c <7% (<53 mmol/mol) with no body weight gain (36% vs. 19% or 16%), and HbA1c <7% (<53 mmol/mol) with no body weight gain and no documented symptomatic hypoglycaemia (plasma glucose ≤3.9 mmol/L; 28% vs. 15% or 15%). The incidence rates of documented symptomatic hypoglycaemia were 29.0%, 27.9% and 12.1% for iGlarLixi, iGlar and Lixi, respectively. CONCLUSIONS: Adults with T2D and HbA1c ≥64 mmol/mol (≥8%) despite two OADs at screening achieved better glycaemic control with iGlarLixi versus iGlar or Lixi, without increased risk of hypoglycaemia versus iGlar.

COPD Population in US Primary Care: Data From the Optimum Patient Care DARTNet Research Database and the Advancing the Patient Experience in COPD Registry.

PURPOSE: To describe demographic and clinical characteristics of chronic obstructive pulmonary disease patients managed in US primary care. METHODS: This was an observational registry study using data from the Chronic Obstructive Pulmonary Disease (COPD) Optimum Patient Care DARTNet Research Database from which the Advancing the Patient Experience COPD registry is derived. Registry patients were aged ≥35 years at diagnosis. Electronic health record data were collected from both registries, supplemented with patient-reported information/outcomes from the Advancing the Patient Experience registry from 5 primary care groups in Texas, Ohio, Colorado, New York, and North Carolina (June 2019 through November 2020). RESULTS: Of 17,192 patients included, 1,354 were also in the Advancing the Patient Experience registry. Patients were predominantly female (56%; 9,689/17,192), White (64%; 9,732/15,225), current/ex-smokers (80%; 13,784/17,192), and overweight/obese (69%; 11,628/16,849). The most commonly prescribed maintenance treatments were inhaled corticosteroid with a long-acting ß2-agonist (30%) and inhaled corticosteroid with a long-acting muscarinic antagonist (27%). Although 3% (565/17,192) of patitents were untreated, 9% (1,587/17,192) were on short-acting bronchodilator monotherapy, and 4% (756/17,192) were on inhaled corticosteroid monotherapy. Despite treatment, 38% (6,579/17,192) of patients experienced 1 or more exacerbations in the last 12 months. These findings were mirrored in the Advancing Patient Experience registry with many patients reporting high or very high impact of disease on their health (43%; 580/1,322), a breathlessness score 2 or more (45%; 588/1,315), and 1 or more exacerbation in the last 12 months (50%; 646/1,294). CONCLUSIONS: Our findings highlight the high exacerbation, symptom, and treatment burdens experienced by COPD patients managed in US primary care, and the need for more real-life effectiveness trials to support decision making at the primary care level.

Pharmacologic Approaches to Glycemic Treatment of Type 2 Diabetes: Synopsis of the 2020 American Diabetes Association's Standards of Medical Care in Diabetes Clinical Guideline.

DESCRIPTION: The American Diabetes Association (ADA) updates the Standards of Medical Care in Diabetes annually to provide clinicians, patients, researchers, payers, and other interested parties with evidence-based recommendations for the diagnosis and management of diabetes. METHODS: To develop the 2020 Standards, the ADA Professional Practice Committee, comprising physicians, adult and pediatric endocrinologists, diabetes educators, registered dietitians, epidemiologists, pharmacists, and public health experts, continuously searched MEDLINE (English language only) from 15 October 2018 through August-September 2019 for pertinent studies, including high-quality trials that addressed pharmacologic management of type 2 diabetes. The committee selected and reviewed the studies, developed the recommendations, and solicited feedback from the larger clinical community. RECOMMENDATIONS: This synopsis focuses on guidance relating to the pharmacologic treatment of adults with type 2 diabetes. Recommendations address oral and noninsulin injectable therapies, insulin treatment, and combination injectable therapies. Results of recent large trials with cardiovascular and renal outcomes are emphasized.

2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group.

The 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group was coordinated and supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health. It is designed to improve patient care and support informed decision making about asthma management in the clinical setting. This update addresses six priority topic areas as determined by the state of the science at the time of a needs assessment, and input from multiple stakeholders:A rigorous process was undertaken to develop these evidence-based guidelines. The Agency for Healthcare Research and Quality's (AHRQ) Evidence-Based Practice Centers conducted systematic reviews on these topics, which were used by the Expert Panel Working Group as a basis for developing recommendations and guidance. The Expert Panel used GRADE (Grading of Recommendations, Assessment, Development and Evaluation), an internationally accepted framework, in consultation with an experienced methodology team for determining the certainty of evidence and the direction and strength of recommendations based on the evidence. Practical implementation guidance for each recommendation incorporates findings from NHLBI-led patient, caregiver, and clinician focus groups. To assist clincians in implementing these recommendations into patient care, the new recommendations have been integrated into the existing Expert Panel Report-3 (EPR-3) asthma management step diagram format.

Diabetes Technology: Review of the 2019 American Diabetes Association Standards of Medical Care in Diabetes.

Description: The American Diabetes Association (ADA) annually updates its Standards of Medical Care in Diabetes to provide clinicians, patients, researchers, payers, and other interested parties with evidence-based recommendations for the diagnosis and management of patients with diabetes. Methods: The ADA Professional Practice Committee comprises physicians, adult and pediatric endocrinologists, diabetes educators, registered dietitians, epidemiologists, pharmacists, and public health experts. To develop the 2019 standards, the committee continuously searched MEDLINE through November 2018 to consider and review studies, particularly high-quality trials including persons with diabetes, for potential incorporation into recommendations. It also solicited feedback from the larger clinical community. Recommendations: This synopsis focuses on selected guidance relating to use of diabetes technology in adults with diabetes. Recommendations address self-monitoring of blood glucose, continuous glucose monitors, and automated insulin delivery systems.

When basal insulin is not enough: A dose-response relationship between insulin glargine 100 units/mL and glycaemic control.

AIMS: A post-hoc analysis to assess the impact in people with type 2 diabetes, of increasing doses of basal insulin on glycaemic measures, body weight and hypoglycaemia. RESEARCH DESIGN AND METHODS: We included data from prospective, randomized controlled treat-to-target trials of ≥24 weeks' duration in people with type 2 diabetes, uncontrolled on metformin and sulphonylureas, and treated with insulin glargine 100 units/mL (U100), who had at least six fasting plasma glucose (FPG) measurements. The impact of insulin dose on glycated haemoglobin (HbA1c) values, FPG, hypoglycaemia incidence (<3.9 mmol/L [70 mg/dL]), and body weight was analysed. A total of 458 participants from three eligible trials were included. RESULTS: The observed relationship between higher basal insulin doses and glycaemic control was non-linear, with increasing insulin dose leading to smaller reductions in FPG and HbA1c for doses >0.3 IU/kg/d, with a plateauing effect at 0.5 IU/kg/d. Total daily dose of insulin >0.5 IU/kg/d resulted in greater weight gain, but without higher rates of hypoglycaemia, compared with insulin doses ≤0.5 IU/kg/d. CONCLUSIONS: This analysis indicates that basal insulin doses >0.5 IU/kg/d have diminishing additional impact on improving glycaemic measures, with the disadvantage of additional weight gain. Clinicians should consider anti-hyperglycaemic treatment intensification at doses approaching 0.5 IU/kg/d.

Initiating therapy in patients newly diagnosed with type 2 diabetes: Combination therapy vs a stepwise approach.

There is clear evidence that achieving glycaemic targets reduces the risk of developing complications as a result of type 2 diabetes (T2D). Many patients, however, continue to have suboptimal glycaemic control because of issues that include unclear advice on how to achieve these targets as well as clinical inertia. The two management approaches recommended for patients newly diagnosed with T2D are stepwise and combination therapy, each of which has advantages and disadvantages. Stepwise therapy may result in good patient adherence and allow greater individualization of therapy, and minimization of side effects and cost, and so may be appropriate for patients who are closer to goal. Stepwise therapy, however, may also lead to frequent delays in achieving glycaemic goals and longer exposure to hyperglycaemia. Combination therapy, which is now emerging as an important therapy option, has a number of potential advantages over stepwise therapy, including reduction in clinical inertia and earlier and more frequent achievement of glycated haemoglobin goals by targeting multiple pathogenic mechanisms simultaneously, which may more effectively delay disease progression. Compared with stepwise therapy, the disadvantages of combination therapy include reduced patient adherence resulting from complex, multi-drug regimens, difficulty determining the cause of poor efficacy and/or side effects, patient refusal to accept disease, and higher cost. Fixed-dose and fixed-ratio combinations are novel therapeutic approaches which may help address several issues of treatment complexity and patient burden associated with combination therapy comprising individual drugs. The choice of which drugs to administer and the decision to use stepwise vs combination therapy, however, should always be made on an individualized basis.

Treatment of Type 1 Diabetes: Synopsis of the 2017 American Diabetes Association Standards of Medical Care in Diabetes.

DESCRIPTION: The American Diabetes Association (ADA) annually updates Standards of Medical Care in Diabetes to provide clinicians, patients, researchers, payers, and other interested parties with evidence-based recommendations for the diagnosis and management of patients with diabetes. METHODS: For the 2017 Standards of Care, the ADA Professional Practice Committee did MEDLINE searches from 1 January 2016 to November 2016 to add, clarify, or revise recommendations on the basis of new evidence. The committee rated the recommendations as A, B, or C, depending on the quality of evidence, or E for expert consensus or clinical experience. The Standards of Care were reviewed and approved by the Executive Committee of the ADA Board of Directors, which includes health care professionals, scientists, and laypersons. Feedback from the larger clinical community informed revisions. RECOMMENDATION: This synopsis focuses on recommendations from the 2017 Standards of Care about monitoring and pharmacologic approaches to glycemic management for type 1 diabetes.

Pharmacologic Therapy for Type 2 Diabetes: Synopsis of the 2017 American Diabetes Association Standards of Medical Care in Diabetes.

DESCRIPTION: The American Diabetes Association (ADA) annually updates the Standards of Medical Care in Diabetes to provide clinicians, patients, researchers, payers, and other interested parties with evidence-based recommendations for the diagnosis and management of patients with diabetes. METHODS: For the 2017 Standards, the ADA Professional Practice Committee updated previous MEDLINE searches performed from 1 January 2016 to November 2016 to add, clarify, or revise recommendations based on new evidence. The committee rates the recommendations as A, B, or C, depending on the quality of evidence, or E for expert consensus or clinical experience. The Standards were reviewed and approved by the Executive Committee of the ADA Board of Directors, which includes health care professionals, scientists, and laypersons. Feedback from the larger clinical community informed revisions. RECOMMENDATIONS: This synopsis focuses on recommendations from the 2017 Standards about pharmacologic approaches to glycemic treatment of type 2 diabetes.

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.

The Use of Albuterol/Budesonide as Reliever Therapy to Reduce Asthma Exacerbations.

Prevention of asthma exacerbations and reduction of systemic corticosteroid burden remain unmet needs in asthma. US asthma guidelines recommend concomitant short-acting ß2-agonist (SABA) and inhaled corticosteroid (ICS) as an alternative reliever at step 2. The Food and Drug Administration approved a pressurized metered-dose inhaler containing albuterol and budesonide for as-needed treatment or prevention of bronchoconstriction and for reducing exacerbation risk in patients with asthma aged ≥18 years. This combination is approved for use as a reliever with or without maintenance therapy, but it is not indicated for maintenance therapy (or for single maintenance and reliever therapy). Intervening with as-needed SABA-ICS during the window of opportunity to reduce inflammation during loss of asthma control can reduce exacerbation risk, by exerting both genomic and nongenomic anti-inflammatory effects. We propose that the use of albuterol-budesonide rather than albuterol as a reliever to manage episodic symptoms driven by acute bronchoconstriction and airway inflammation can improve outcomes. This combination approach, shown to decrease asthma exacerbations and oral corticosteroid burden in patients with moderate-to-severe asthma, represents a paradigm shift for asthma treatment in the United States. Further safety and efficacy studies should provide evidence that this type of reliever should be standard of care.

Implications of Cardiopulmonary Risk for the Management of COPD: A Narrative Review.

Chronic obstructive pulmonary disease (COPD) constitutes a major global health burden and is the third leading cause of death worldwide. A high proportion of patients with COPD have cardiovascular disease, but there is also evidence that COPD is a risk factor for adverse outcomes in cardiovascular disease. Patients with COPD frequently die of respiratory and cardiovascular causes, yet the identification and management of cardiopulmonary risk remain suboptimal owing to limited awareness and clinical intervention. Acute exacerbations punctuate the progression of COPD in many patients, reducing lung function and increasing the risk of subsequent exacerbations and cardiovascular events that may lead to early death. This narrative review defines and summarises the principles of COPD-associated cardiopulmonary risk, and examines respiratory interventions currently available to modify this risk, as well as providing expert opinion on future approaches to addressing cardiopulmonary risk.