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.

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.

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.

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.

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.

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.

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.

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.

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.

Uncovering undetected hypoglycemic events.

Hypoglycemia is the rate-limiting factor that often prevents patients with diabetes from safely and effectively achieving their glycemic goals. Recent studies have reported that severe hypoglycemia is associated with a significant increase in the adjusted risks of major macrovascular events, major microvascular events, and mortality. Minor hypoglycemic episodes can also have serious implications for patient health, psychological well being, and adherence to treatment regimens. Hypoglycemic events can impact the health economics of the patient, their employer, and third-party payers. Insulin treatment is a key predictor of hypoglycemia, with one large population-based study reporting an overall prevalence of 7.1% (type 1 diabetes mellitus) and 7.3% (type 2 diabetes mellitus) in insulin-treated patients, compared with 0.8% in patients with type 2 diabetes treated with an oral sulfonylurea. Patients with type 1 diabetes typically experience symptomatic hypoglycemia on average twice weekly and severe hypoglycemia once annually. The progressive loss of islet cell function in patients with type 2 diabetes results in a higher risk of both symptomatic and unrecognized hypoglycemia over time. Patients with diabetes who become hypoglycemic are also more susceptible to developing defective counter-regulation, also known as hypoglycemia awareness autonomic failure, which is life-threatening and must be aggressively addressed. In patients unable to recognize hypoglycemia symptoms, frequent home monitoring or use of continuous glucose sensors are critical. Primary care physicians play a key role in the prevention and management of hypoglycemia in patients with diabetes, particularly in those requiring intensive insulin therapy, yet physicians are often unaware of the multitude of consequences of hypoglycemia or how to deal with them. Careful monitoring, adherence to guidelines, and use of optimal treatment combinations are all important steps toward improving care in patients with diabetes. The most important goals are for primary care physicians to recognize that every patient treated with antihyperglycemic medications is at risk of iatrogenic hypoglycemia and to ask patients about hypoglycemia at every visit.

Comparing the efficacy, safety, and utility of intensive insulin algorithms for a primary care practice.

Diabetes management is firmly based within the primary care community. Landmark randomized, controlled trials have demonstrated that even modest reductions in glycated hemoglobin (HbA(1c)) can yield improvements in economic and medical end-points. Diabetes is a chronic, progressive disease associated with loss of pancreatic ß-cell function. Therefore, most patients will eventually require insulin therapies in order to achieve their individualized targeted HbA(1c) as their ß-cell function and mass wanes. Although clinicians understand the importance of early insulin initiation, there is little agreement as to when to introduce insulin as a therapeutic option. Once initiated, questions remain as to whether to allow the patients to self-titrate their dose or whether the dosing should be tightly regulated by the clinician. Physicians have many evidence-based basal insulin protocols from which to choose, all of which have been shown to drive HbA1c levels to the American Diabetes Association target of ≤7%. This article will discuss ways by which insulin therapies can be effectively introduced to patients within busy primary care practices. Published evidence-based basal insulin protocols will be evaluated for safety and efficacy.

Insulin initiation and intensification in patients with T2DM for the primary care physician.

Type 2 diabetes mellitus (T2DM) is characterized by both insulin resistance and inadequate insulin secretion. All patients with the disease require treatment to achieve and maintain the target glycosylated hemoglobin (A1C) level of 6.5%-7%. Pharmacological management of T2DM typically begins with the introduction of oral medications, and the majority of patients require exogenous insulin therapy at some point in time. Primary care physicians play an essential role in the management of T2DM since they often initiate insulin therapy and intensify regimens over time as needed. Although insulin therapy is prescribed on an individualized basis, treatment usually begins with basal insulin added to a background therapy of oral agents. Prandial insulin injections may be added if glycemic targets are not achieved. Treatments may be intensified over time using patient-friendly titration algorithms. The goal of insulin intensification within the primary care setting is to minimize patients' exposure to chronic hyperglycemia and weight gain, and reduce patients' risk of hypoglycemia, while achieving individualized fasting, postprandial, and A1C targets. Simplified treatment protocols and insulin delivery devices allow physicians to become efficient prescribers of insulin intensification within the primary care arena.

Recognition, prevention, and proactive management of hypoglycemia in patients with type 1 diabetes mellitus.

Hypoglycemia is the key barrier that prevents patients from optimizing glycemic control with the use of pharmacotherapeutic interventions. Optimal glycemic control for patients with type 1 diabetes (T1DM) includes methods that provide glucose-regulated physiologic insulin replacement or secretion in association with glucose monitoring methods designed to predict and prevent acute extreme changes in glycemic variability. Patients with T1DM experience an average of 2 episodes of symptomatic hypoglycemia each week and at least 1 episode of severe, disabling hypoglycemia annually. Asymptomatic hypoglycemia is common, as shown in studies using continuous glucose monitoring (CGM). Episodes of hypoglycemia (symptomatic and asymptomatic) impair counterregulatory defenses against subsequent events, resulting in the inability to respond to and recover from serious hypoglycemia. This defective counterregulation is known as hypoglycemic-associated autonomic failure. When patients are prescribed a more intensive medication regimen or reinforcing lifestyle interventions, such as medical nutrition therapy and exercise therapy, providers should also assess their ability to proactively identify and manage hypoglycemia. Although self-monitoring of blood glucose regimens, such as pre- and post-meal and periodic middle-of-the-night glucose testing, can help predict the risk of developing hypoglycemia, CGM technology allows patients to receive real-time notification of impending events either through preset alarms or simply by looking at the device display. This review explores the utility of initiating CGM within the primary care setting for patients at high risk for developing hypoglycemia.