Evolution and Revolution-Our Changing Relationship With Insulin.

Type 2 diabetes is a progressive condition with a complex pathophysiology. Over time, additional therapies are needed to maintain glycemic control. It is well known that, by the time of diagnosis, beta cell function has already declined by 50% to 80%. When the body is no longer able to make enough insulin to control blood glucose levels, insulin replacement therapy is needed. However, barriers to initiation of insulin therapy are multifactorial and contribute to delays in treatment and consequent uncontrolled glycemia; this leads to an increased risk of disease complications. In this roundtable discussion, the authors review how people living with type 2 diabetes and their healthcare providers view the initiation of insulin. Other topics include the benefits of longer-acting basal insulin analogs compared with long-acting analogs. The authors emphasize the importance of early and positive conversations about insulin therapy, as well as the benefits of shared decision-making and the use of the wider medical team for the timely initiation of basal insulin therapy.

Post Hoc Analysis Evaluating the Impact of Antihyperglycemic Background Therapies on Attainment of A1C Targets Without Hypoglycemia in the ACHIEVE Control Pragmatic, Real-Life Study.

BACKGROUND: ACHIEVE Control, a prospective, open-label, randomized, pragmatic, real-life study in insulin-naive people with type 2 diabetes (A1C 8.0-11.0%), demonstrated superiority of insulin glargine 300 units/mL (Gla-300) versus first-generation standard-of-care basal insulin (SOC-BI; glargine 100 units/mL or insulin detemir) in achieving individualized A1C targets without documented symptomatic (glucose ≤3.9 mmol/L [≤70 mg/dL] or <3.0 mmol/L [<54 mg/dL]) or severe hypoglycemia (American Diabetes Association level 3) at 6 months. Noninsulin antihyperglycemic background therapies are commonly used; however, sulfonylureas may increase hypoglycemia risk. This post hoc analysis assessed outcomes according to background therapy. METHODS: Subgroup analyses were performed per concomitant use/nonuse of sulfonylureas, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase 4 inhibitors, or sodium-glucose cotransporter 2 (SGLT2) inhibitors. End points (6 and 12 months) included A1C target attainment without documented symptomatic or severe hypoglycemia, A1C target attainment, and absence of documented symptomatic or severe hypoglycemia. RESULTS: Odds ratios (ORs) at 12 months mostly favored Gla-300 versus SOC-BI across subgroups except in analysis of SGLT2 inhibitors, in which ORs were similar. Among sulfonylurea users, ORs at 12 months strongly favored Gla-300 versus SOC-BI for all end points, particularly A1C target achievement without documented symptomatic hypoglycemia (glucose ≤3.9 mmol/L [≤70 mg/dL]; OR 1.25, 95% CI 1.02-1.53) or severe hypoglycemia and achievement of no documented symptomatic hypoglycemia (glucose <3.0 mmol/L [<54 mg/dL]; OR 1.25, 95% CI 1.02-1.52) or severe hypoglycemia. CONCLUSION: The results suggest that, in insulin-naive people with type 2 diabetes, Gla-300 is effective with a risk of hypoglycemia that is lower than or similar to that of SOC-BI regardless of background medication. Individuals receiving concomitant sulfonylureas were more likely to remain without symptomatic or severe hypoglycemia with Gla-300.

Initiative to Improve Evidence-Based Chronic Obstructive Pulmonary Disease Hospitalist Care Using a Novel On-Line Gamification Patient Simulation Tool: A Prospective Study.

Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality. Much of the disease burden comes from exacerbations requiring hospitalization. Unwarranted care variation and divergence from evidence-based COPD management guidelines among hospitalists is a leading driver of the poor outcomes and excess costs associated with COPD-related hospitalizations. We engaged with Novant Health hospitalists to determine if measurement and feedback using fixed-choice simulated patients improves evidence-based care delivery and reduces costs. We created a series of gamified acute-care COPD case simulations with real-time feedback over 16 weeks then performed a year-over-year analytic comparison of the cost, length of stay (LOS), and revisits over the six months prior to the introduction of the simulated patients, the four months while caring for the simulated patients, and the six months after. In total, 245 hospitalists from 15 facilities at Novant Health participated. At baseline, the overall quality-of-care was measured as 58.4% + 12.3%, with providers correctly identifying COPD exacerbation in 92.4% of cases but only identifying the grade and group in 61.9% and 49.5% of cases, respectively. By the study end, the quality-of-care had improved 10.5% (p < 0.001), including improvements in identifying the grade (+9.7%, p = 0.044) and group (+8.4%, p = 0.098). These improvements correlated with changes in real-world performance data, including a 19% reduction in COPD-related pharmacy costs. Overall, the annualized impact of COPD improvements led to 233 fewer inpatient days, 371 fewer revisit days, and inpatient savings totaling nearly $1 million. Engaging practicing providers with patient simulation-based serial measurements and gamified evidence-based feedback potentially reduces inpatient costs while simultaneously reducing patient LOS and revisit rates.

Switching between GLP-1 receptor agonists in clinical practice: Expert consensus and practical guidance.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an established treatment for patients with type 2 diabetes (T2D). Differences between GLP-1RAs in pharmacokinetics, dosing regimens and clinical effects, including cardiovascular (CV) outcomes, mean there may be benefits to switching from one to another. However, clinical guidance on switching is lacking and data from clinical trials are limited. This article provides a clinical perspective and consensus on the benefits of switching between GLP-1RAs, the triggers for switching and how best to manage this in clinical practice. Once weekly (OW) semaglutide is used as an example to illustrate how the authors might switch to a different GLP-1RA in clinical practice. METHODS: Literature was searched and perspectives from 10 healthcare professionals with experience in switching patients with T2D to OW semaglutide from another GLP-1RA were collated. RESULTS: Medical triggers for switching to another GLP-1RA included HbA1c targets not being met, a desire for additional weight loss, poor adherence, patients moving to increased CV risk status and adverse effects with the current GLP-1RA. Non-medical triggers for switching included patient preference, cost, formulary changes and insurance mandates. Once the decision to switch is made, an individualised approach is recommended, based on considerations that include reimbursement requirements, treatment duration with (and dose of) previous GLP-1RA, the patient's experience initiating the prior GLP-1RA, any concomitant treatment and clinical characteristics. When switching, it is important to emphasise that treatment burden will not increase and that if gastrointestinal adverse effects occur, they are typically transient. Any transient gastrointestinal adverse effects that may occur (or recur) when switching to another GLP-1RA can be reduced by slow up-titration and advising patients to reduce food portion sizes and fat intake. CONCLUSION: Switching from one GLP-1RA to another, such as OW semaglutide, can provide clinical benefits and may delay the need for treatment intensification.

How Effective Is the Fixed-Ratio Combination of Insulin Degludec and Liraglutide (IDegLira) in Different Patient Populations, and When Should It Be Used in Clinical Practice?

The efficacy and safety of the fixed-ratio combination of insulin degludec (degludec) and liraglutide (IDegLira) were confirmed in the DUAL clinical trial program, in which IDegLira demonstrated superior or noninferior glycemic control over comparators in addition to its low risks of hypoglycemia and weight gain. This article identifies the patient types for whom IDegLira is most appropriate by reviewing the DUAL results and subsequent post hoc analyses and presenting real-world cases in which IDegLira has been used effectively in U.S. clinical practice. In the clinic, IDegLira has been used effectively when patients wanted to avoid more complex injectable regimens, particularly those with renal insufficiency for whom treatment options are limited.

Insulin glargine 300 U/mL versus first-generation basal insulin analogues in insulin-naïve adults with type 2 diabetes: 12-month outcomes of ACHIEVE Control, a prospective, randomized, pragmatic real-life clinical trial.

AIM: To report the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) versus standard-of-care basal insulin analogues (SOC-BI) at 12 months in the ACHIEVE Control trial, which is a prospective pragmatic randomized real-life study in insulin-naïve adults with type 2 diabetes (T2D). METHODS: A total of 3304 insulin-naïve adults with T2D and glycated haemoglobin (HbA1c) concentration of 64 to 97 mmol/mol (8.0% to 11.0%) after ≥1 year of treatment with two or more antihyperglycaemic agents were randomized to Gla-300 or SOC-BI. Key secondary endpoints included HbA1c target attainment without documented symptomatic (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia at 12 months. RESULTS: At 12 months, 26.1% (Gla-300) and 23.7% (SOC-BI) of adults achieved HbA1c targets without documented symptomatic (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia (odds ratio [OR] 1.14, 95% confidence interval [CI] 0.97-1.35); 33.0% and 29.5%, respectively, achieved HbA1c targets without documented symptomatic (<3.0 mmol/L [<54 mg/dL]) or severe hypoglycaemia (OR 1.19, 95% CI 1.02-1.38). The OR for HbA1c target achievement was 1.15 (95% CI 0.99-1.34), and favoured Gla-300 versus SOC-BI for absence of documented symptomatic or severe hypoglycaemia at 12 months for both ≤3.9 mmol/L (≤70 mg/dL; OR 1.21, 95% CI 1.05-1.40) and < 3.0 mmol/L (<54 mg/dL; OR 1.26, 95% CI 1.07-1.48). CONCLUSION: Gla-300 tended to be associated with lower hypoglycaemia risk than SOC-BI in real-world clinical practice during the 12-month follow-up.

The Pleiotropic Effects of Sodium-Glucose Cotransporter-2 Inhibitors: Beyond the Glycemic Benefit.

Type 2 diabetes (T2D) is associated with an increased risk of macro- and microvascular complications, including cardiovascular disease (CVD), heart failure (HF), and chronic kidney disease (CKD). Of the currently available glucose-lowering therapies, sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are the only class to target the pathophysiologic increase in renal glucose reabsorption in patients with T2D. In CV outcomes trials of SGLT-2is in patients with T2D and established CVD or varying levels of CV risk, empagliflozin, canagliflozin, and dapagliflozin were associated with significant improvements in the risk of composite CV and renal outcomes compared with placebo that extended beyond their glycemic effects. Real-world observational studies have also reported improvements in CV outcomes with SGLT-2is compared with other glucose-lowering therapy in routine clinical practice. This review describes the pleiotropic effects of SGLT-2is and discusses the potential mechanisms for these effects as well as how they potentially provide benefits beyond glycemic control in patients with T2D. These favorable nonglycemic effects indicate that SGLT-2is may be of particular benefit in patients with diabetic complications, such as CVD, HF, or CKD. Ongoing large randomized trials in specific patient populations, including those with CVD, HF, or CKD (with or without T2D), may help to confirm the benefits of SGLT-2is in these patients and further elucidate the potential mechanisms of their pleiotropic effects. FUNDING: AstraZeneca.

Insulin Initiation and Titration in Patients With Type 2 Diabetes.

Insulin initiation and titration can be challenging for many primary care providers who are involved in the treatment of patients with type 2 diabetes. Despite the introduction of advanced insulin analogs and improvements in insulin delivery devices, many patients with type 2 diabetes continue to experience suboptimal glycemic control. With an increasing number of treatment options available, type 2 diabetes management is moving away from a "one-size-fits-all" approach and toward individualized treatment regimens based on particular patient needs. Given this, nurse practitioners, physician assistants, pharmacists, and certified diabetes educators are becoming increasingly valuable resources in busy primary care practices.

Real-world evidence in diabetes: relevance to clinical practice.

Real-world studies may be distinguished from traditional randomized controlled trials (RCTs) based on the study population and the setting in which the research is conducted. While RCTs are the gold standard for evaluating the efficacy and safety of new therapeutic interventions, they are typically conducted in specialized environments that may lack the everyday reality of clinical, home, and community settings. There is often a gap between efficacy shown in RCTs and the effectiveness observed in real-world settings. Real-world studies and resultant real-world data can be used to develop real-world evidence (RWE). RWE adds to the evidence from RCTs by providing additional results obtained from a broader patient population outside the constraints of RCTs to evaluate what is happening in usual clinical practice. Thus, RWE is useful in determining the effectiveness and safety of an intervention in clinical practice, and it can also provide information on health care resource utilization and costs, which are not typically evaluated in RCTs.

A Quality Collaboration in Heart Failure and Pneumonia Inpatient Care at Novant Health: Standardizing Hospitalist Practices to Improve Patient Care and System Performance.

BACKGROUND: Heart failure and pneumonia are among the most measured and expensive conditions to treat in the United States across all payer types and are top of mind for value-driven hospital organizations and payers seeking to not only improve the quality of care for patients but also reduce unnecessary spending. Care standardization potentially leads to better patient outcomes and reduced excess costs but is a difficult objective to achieve. METHODS: A pre-post analysis of clinical practice, patient outcomes, and cost was designed to determine if serial measurement and feedback using simulated patients improves patient care quality and reduces costs for two common conditions cared for by hospitalists: pneumonia and heart failure. Care decisions measured using the simulations were compared to patient-level data collected by the system. RESULTS: Intrafacility care variation seen among Novant Health's 11 facilities employing hospitalists decreased from 14.9% to 8.5%, and overall quality-of-care scores by individual providers improved by 14.6 percentage points from study start to end. Overall, care changes (for example, troponin usage, palliative care consults, beta blocker orders) documented in the simulated patients matched the available patient-level data. Care standardization around evidence-based practices, as measured by the simulations, was associated with appreciable decreases in patient length of stay and readmissions, amounting to nearly $1.1 million in savings for Novant Health. CONCLUSION: An approach using simulated patients that includes serial measurement and feedback may help significantly reduce practice variation between different facilities in a health system and reduce costs substantially without negatively affecting outcomes.

Improved Treatment Engagement Among Patients with Diabetes Treated with Insulin Glargine 300 U/mL Who Participated in the COACH Support Program.

INTRODUCTION: Persistence with basal insulin therapy can be suboptimal, despite recent improvements in insulin formulations and delivery systems. Patient support programs may help increase adherence. This study evaluated the impact of the Toujeo® COACH support program, which provides patients with continuing and individualized education and advice on lifestyle changes, by assessing its effect on number of refills and days on therapy. METHODS: The study population included 1724 patients with diabetes who filled a first prescription for insulin glargine 300 U/mL (Gla-300) between April and December 2015 and received a welcome call from a Guide, and 1724 matched control patients from the Symphony Health Integrated Dataverse® prescription claims database. Control patients received Gla-300 but did not enroll in the program. These patients were matched based on age, gender, location, prior use of insulin, insulin dose, number of concomitant drugs, and copay tier. RESULTS: The COACH and control groups comprised 52% men and 48% women; 22% were aged 18-47 years, 23% were 48-55 years, 27% 56-61 years, and 28% ≥ 62 years. Most (99%) had used insulin in the year before receiving the welcome call. At 6 months, patients in the COACH group had refilled their prescription 3.2 times on average, compared with 2.4 times for control patients (P < 0.0001); at 9 months, the average number of refills was 4.7 and 3.6, respectively (P < 0.0001). The average number of days on therapy at 6 months was 102.2 days in the COACH group and 81.5 days in the control group (P < 0.0001); at 9 months, the average number of days on therapy was 151.9 and 121.6, respectively (P < 0.0001). CONCLUSION: Patients in the COACH program were significantly more likely to refill their prescriptions and stay on therapy. Patient support programs such as the COACH program could be an effective way to help improve diabetes care. FUNDING: Sanofi US, Inc. and McKesson Corporation.

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.

Insulin glargine 300 units/mL: a guide for healthcare professionals involved in the management of diabetes.

Insulin glargine 300 units/mL: Insulin glargine 300 units/mL (Gla-300) is a formulation of insulin glargine that delivers the same number of insulin units in one-third of the injectable volume of insulin glargine 100 units/mL (Gla-100). Glucose control: Recently approved in the United States and in Europe for use in type 1 and type 2 diabetes, Gla-300 has a more constant and evenly distributed glucose-lowering effect compared with Gla-100, with a duration of action beyond 24 hours and lower within-day and between-day intra-individual variability in blood glucose levels. These benefits translate into predictable and sustained glucose control from a once-daily injection, with potential for fewer hypoglycemia episodes and less weight gain. CASE STUDIES: Case studies are presented to highlight the potential clinical benefits and considerations associated with initiating treatment with Gla-300 in people with type 1 and type 2 diabetes.