Maintenance of glycaemic control with liraglutide versus oral antidiabetic drugs as add-on therapies in patients with type 2 diabetes uncontrolled with metformin alone: A randomized clinical trial in primary care (LIRA-PRIME).

AIM: To compare (in the LIRA-PRIME [NCT02730377], a randomized open-label trial), the efficacy of liraglutide in controlling glycaemia versus an oral antidiabetic drug (OAD) in patients with uncontrolled type 2 diabetes (T2D), despite metformin use in a primary care setting (n = 219 sites, n = 9 countries). MATERIALS AND METHODS: Adults (n = 1991) with T2D (HbA1c 7.5%-9.0%) receiving metformin were randomized 1:1 to liraglutide (≤1.8 mg/d) or one OAD, selected by the investigator, added to metformin, for up to 104 weeks. Primary endpoint: time to inadequate glycaemic control (HbA1c > 7.0%) at two scheduled consecutive visits after week 26. Outcomes were assessed for liraglutide versus a pooled OAD group, and (post hoc) liraglutide versus sodium-glucose co-transporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, and sulphonylureas individually. RESULTS: Among randomized patients (liraglutide, n = 996; OAD, n = 995), 47.6% were female, mean age was 57.4 years and mean HbA1c was 8.2%. Median time to inadequate glycaemic control was 44 weeks longer with liraglutide versus OAD (109 weeks [25% percentile, 38; 75% percentile, not available] vs. 65 weeks [25% percentile, 35; 75% percentile, 107], P < .0001). Changes in HbA1c and body weight at week 104 or at premature treatment discontinuation significantly favoured liraglutide over OAD. Hypoglycaemia rates were comparable between groups and few patients discontinued because of adverse events (liraglutide, 7.9% [n = 79]; OAD, 4.1% [n = 41]). Similar results were observed in the post hoc analysis for liraglutide versus individual OAD classes. CONCLUSIONS: Glycaemic control was better maintained with liraglutide versus OAD, supporting liraglutide use when intensifying therapy in primary care patients with T2D.

American Association of Clinical Endocrinology Clinical Practice Guideline: The Use of Advanced Technology in the Management of Persons With Diabetes Mellitus.

OBJECTIVE: To provide evidence-based recommendations regarding the use of advanced technology in the management of persons with diabetes mellitus to clinicians, diabetes-care teams, health care professionals, and other stakeholders. METHODS: The American Association of Clinical Endocrinology (AACE) conducted literature searches for relevant articles published from 2012 to 2021. A task force of medical experts developed evidence-based guideline recommendations based on a review of clinical evidence, expertise, and informal consensus, according to established AACE protocol for guideline development. MAIN OUTCOME MEASURES: Primary outcomes of interest included hemoglobin A1C, rates and severity of hypoglycemia, time in range, time above range, and time below range. RESULTS: This guideline includes 37 evidence-based clinical practice recommendations for advanced diabetes technology and contains 357 citations that inform the evidence base. RECOMMENDATIONS: Evidence-based recommendations were developed regarding the efficacy and safety of devices for the management of persons with diabetes mellitus, metrics used to aide with the assessment of advanced diabetes technology, and standards for the implementation of this technology. CONCLUSIONS: Advanced diabetes technology can assist persons with diabetes to safely and effectively achieve glycemic targets, improve quality of life, add greater convenience, potentially reduce burden of care, and offer a personalized approach to self-management. Furthermore, diabetes technology can improve the efficiency and effectiveness of clinical decision-making. Successful integration of these technologies into care requires knowledge about the functionality of devices in this rapidly changing field. This information will allow health care professionals to provide necessary education and training to persons accessing these treatments and have the required expertise to interpret data and make appropriate treatment adjustments.

Trial design and baseline data for LIRA-PRIME: A randomized trial investigating the efficacy of liraglutide in controlling glycaemia in type 2 diabetes in a primary care setting.

AIMS: Using a pragmatic approach, the LIRA-PRIME trial aims to address a knowledge gap by comparing efficacy in controlling glycaemia with glucagon-like peptide-1 analog liraglutide vs oral antidiabetic drugs (OADs) in patients with type 2 diabetes (T2D) uncontrolled with metformin monotherapy in primary care practice. We report the study design and patient baseline characteristics. MATERIALS AND METHODS: This 104-week, two-arm, open-label, active-controlled trial is active in 219 primary care practices across nine countries. At screening, eligible patients with T2D were at least 18 years of age, had been using a stable daily dose of metformin ≥1500 mg or the maximum tolerated dose for ≥60 days, and had a glycated haemoglobin (HbA1c) of 7.5% to 9.0%, measured ≤90 days before screening. Patients were randomized (1:1) to liraglutide or OAD, both in addition to pre-trial metformin. Individual OADs were chosen by the treating physician based on local guidelines. The primary endpoint is time to inadequate glycaemic control, defined as HbA1c above 7.0% at two scheduled consecutive visits after the first 26 weeks of treatment. RESULTS: The trial randomized 1997 patients with a mean (standard deviation) age of 56.9 (10.8) years, T2D duration of 7.2 (5.9) years (range, <1-47 years), and HbA1c of 8.2%. One-fifth of patients had a history of diabetes complications, and most were overweight (24.8%) or had obesity (65.3%). CONCLUSIONS: This pragmatically designed, large-scale, multinational, randomized clinical trial will help guide treatment decisions for patients with T2D who are inadequately controlled with metformin monotherapy and treated in primary care.

Rationale use of GLP-1 receptor agonists in patients with type 1 diabetes.

Clinicians and patients are rapidly adapting GLP-1 receptor agonists as efficacious and safe therapeutic options for managing type 2 diabetes (T2DM). GLP-1 receptor agonists stimulate insulin production and secretion from the pancreatic ß cells in a glucose-dependent manner, improve gastric emptying, favor weight reduction, and reduce postabsorptive glucagon secretion from pancreatic α cells. GLP-1 receptor activity is impaired in patients with T2DM. GLP-1 secretion and subsequent physiologic actions in patients with type 1 diabetes (T1DM) is ill-defined. Some researchers have suggested that the use of GLP-1 receptor agonists in T1DM may reduce excessive postprandial glucagon secretion allowing patients to reduce their total daily dose of exogenous insulin. Hypoglycemia risk may also be minimized in T1DM as glucagon counter-regulation can be preserved to some degree via the glucose-dependent action of the GLP-1 receptor agonists. This paper will consider the physiologic and pharmacologic benefits of adding GLP-1 receptor agonists to therapeutic regimens of patients with T1DM.

Practical Application of Continuous Glucose Monitoring in Clinical Practice: Case Studies.

The prevalence of diabetes continues to rise exponentially and contributes significantly to morbidity, mortality, and health care resource utilization. Individuals with diabetes have adopted continuous glucose monitoring (CGM) as their preferred method for glucose measurement. Primary care clinicians should become proficient in utilizing this technology in their practices. This case-based article provides practical guidance in CGM interpretation allowing patients to become successful partners in diabetes self-management. Our approach to data interpretation and shared decision-making is applicable to all current CGM systems.

Continuous glucose monitoring overview: features and evidence.

The prevalence of diabetes is growing in the United States at an alarming rate. Early and intensive diagnosis and management of diabetes can reduce the economic burden and improve the societal burden of long-term diabetes-related complications. Healthcare providers practicing in the primary care setting are on the front line of screening, diagnosis, and managing a large majority of persons with diabetes.Until recently, blood glucose monitoring, along with timely A1C measurements, has been the recommended means by which patients can best achieve their prescribed metabolic targets. However, supplies and testing can be costly and burdensome, affecting patient compliance and medication adherence. The recent introduction of integrated diabetes technology including continuous glucose monitoring (CGM) has had a tremendous impact on treating patients to their prescribed glycemic targets safely and efficiently while minimizing their risk of developing treatment-emergent hypoglycemia. Patients who utilize CGM are able to reduce their risk of hospitalizations, minimize work absenteeism, lower their A1C, lower their risk of hypoglycemia, as well as long-term microvascular and macrovascular complications.The American Diabetes Association updated its evidence-based Standards of Medical Care in Diabetes in 2022 around the use of CGM, as has the American Association of Clinical Endocrinology. Because these devices can have a positive effect on the management of persons with diabetes, managed care and healthcare providers should allow technological integration for their patients.

Primary care management of type 2 diabetes: a comparison of the efficacy and safety of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 inhibitors (DPP4is) exert their effects via the incretin system, which augments glucose-dependent insulin secretion in response to nutrient intake (the 'incretin effect'). Both classes are well-established pharmacologic options for the management of glycemic control in individuals with type 2 diabetes (T2D) after failure of first-line metformin; however, they have inherent differences in their mechanisms of action that are reflected in their clinical safety and efficacy profiles. GLP-1RAs have high glycemic efficacy and are associated with weight loss and, in some cases, cardioprotective effects, with a side-effect profile of predominantly transient gastrointestinal adverse events. Most GLP-1RAs are administered as subcutaneous injection, although an oral formulation of one GLP-1RA, semaglutide, has recently become available. DPP4is provide moderate glycemic control, are weight-neutral, and do not offer any cardiovascular benefits, but are generally well tolerated. DPP4is are all administered orally. This narrative review aims to provide guidance for a primary care audience on the similarities and differences between GLP-1RA and DPP4i therapies, with a focus on their mechanism of action, clinical safety, efficacy, and real-world effectiveness. The role of incretin-based therapies in the T2D treatment paradigm, including key considerations for guiding treatment decisions, will also be discussed.

Practical guidance for using the FreeStyle Libre flash continuous glucose monitoring in primary care.

Use of continuous glucose monitoring (CGM) improves clinical outcomes in type 1 diabetes, and significant benefits been demonstrated in patients with type 2 diabetes, including improved glycemic control, better treatment adherence, and an increased understanding of their treatment regimens. Currently, there are two types of CGM systems: real-time CGM (rtCGM) and flash CGM (FCGM). Retrospective analysis of CGM data allows patients and their clinicians to identify glycemic patterns that support and facilitate informed therapy decisions. With the increasing prevalence of diabetes, primary care physicians will be compelled to take on more responsibility for managing patients with diabetes. This article focuses on practical approaches and decision-making strategies for utilizing FCGM in primary care settings.

Implications of Cardiovascular Outcomes Trials in Type 2 Diabetes for Primary Care.

Patients with type 2 diabetes (T2D) are at a greater risk of cardiovascular (CV) morbidity and mortality than their counterparts without diabetes. Worsening glycemic control is associated with increasing risk of CV events and mortality, but glycemic control alone does not appear sufficient to improve CV outcomes. Furthermore, some glucose-lowering drugs have been associated with an increased risk of CV events. As a result, the US Food and Drug Administration (FDA) issued guidance in 2008 for the investigation of CV risk with new diabetes therapies. Numerous CV outcomes trials have since been initiated for drugs in the dipeptidyl peptidase 4 (DPP-4) inhibitors, sodiumglucose cotransporter-2 (SGLT-2) inhibitors, and glucagon-like peptide-1 receptor agonist (GLP-1 RA) classes. CV safety has been confirmed for a number of drugs. More recently, CV benefits have been shown for some SGLT-2 inhibitors and GLP-1 RAs. Primary care physicians should consider medications that can lower CV risk alongside favorable efficacy and safety profiles for treatment of patients with T2D at high CV risk.

Fine-tuning glycemic control using computerized downloading software: a case-based approach.

Diabetes self-management is not always the simplest of tasks. Patients with diabetes do not have a functioning pancreas. They rely on their knowledge to guide them through the complex decisions that must be made continually. Glycemic variability is not always a result of patient noncompliance. In fact, most patients are attempting to maintain normal glycemia. Imagine the frustrations that our patients feel when they do not understand why their blood glucose levels vary so greatly, even if they eat the same foods and participate in the same type of physical activities each day. As physicians, we should provide our patients with the best opportunities, tools, and technologies available to minimize their exposure to glycemic variability, oxidative stress, and long-term diabetes-related complications. SBGM is an essential component in diabetes care. Incorporating computerized software into our practices so that we are able to fine-tune our prescribed treatments is an inexpensive and efficient way to improve the quality of our patients' lives.

Diagnosis and management of type 2 diabetes and prediabetes.

Treatment of type 2 diabetes mellitus (T2DM), a progressive disease, requires early and appropriate therapies, with frequent monitoring and reassessment to make certain goals are attained. Chronic hyperglycemia can cause macrovascular and microvascular complications, many of which may be apparent on initial diagnosis. As beta-cell function deteriorates and insulin resistance intensifies, patients find that oral pharmacologic therapy is becoming less effective at minimizing the effects of chronic hyperglycemia. Eventually, most will require exogenous insulin therapy. Primary care physicians manage over 90% of T2DM patients, so we must have a better understanding of our roles as patient educators, advocates, and medical providers, and do everything in our power to help our patients achieve the lowest and safest glycated hemoglobin (A1C) possible.

Management of diabetes in pregnancy, childhood, and adolescence.

Primary care physicians are likely to become involved with the management of many types of patients who have diabetes, including children and adolescents. Although specialty consultation is necessary for these young patients, the primary care physician often provides a strong cornerstone of therapy revolving around complication surveillance, disease prevention (especially in patients who have gestational diabetes following the completion of their pregnancy), motivation toward making healthy lifestyle choices, and support of the family unit once a new diagnosis of type 1 diabetes mellitus is made. By promoting a healthy lifestyle to high-risk patients, primary care physicians can help delay the onset and reduce the incidence of type 2 diabetes in children and adolescents.

Management of type 1 diabetes.

Although less prevalent than type 2 diabetes, autoimmune type 1 diabetes presents numerous challenges, including many that must be addressed daily. Patients must have appropriate tools to confront and manage their physiologic insulin deficiency syndrome. The vast majority of patients who have type 1 diabetes require a basal insulin to suppress hepatic glucose production in the fasting state, as well as prandial (mealtime) insulin to cover glycemic excursions that occur as carbohydrate absorption occurs in response to meals. Patients need algorithms to self-adjust both their prandial and basal insulin doses. The ultimate goal of all patients who have diabetes is to attain and maintain an A1C as close to normal as possible, while maintaining safety, avoiding hypoglycemia, and minimizing glycemic variability, as close to normal as possible, while maintaining safety and avoiding severe hypoglycemia.

Recognition and management of diabetic neuropathy.

Pain and disability associated with diabetic neuropathy have economic, social, and emotional consequences. Because these complications impact patients during the prime of their lives, physicians should screen and manage patients at risk. Improvement in glycemic and lipid management, glycemic variability, and lifestyle interventions such as smoking cessation should limit disease progression. Patients who have symptomatic disease should be treated, targeting a 50% improvement in pain within 4 weeks. Physicians should also strive to improve function and comorbidities such as sleep disorders, depression, and anxiety. Patient education is critical for treatment adherence and prevention of serious complications. Consequences associated with diabetic neuropathy include nontraumatic amputations and silent ischemia; thus proper foot care and education regarding "warning signs" of silent ischemia are necessary.

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.