Suboptimal monitoring and management in patients with unrecorded stage 3 chronic kidney disease in real-world settings: Insights from REVEAL-CKD.

BACKGROUND: Clinical practice guidelines for patients with chronic kidney disease (CKD) recommend regular monitoring and management of kidney function and CKD risk factors. However, the majority of patients with stage 3 CKD lack a diagnosis code, and data on the implementation of these recommendations in the real world are limited. AIM: To assess the implementation of guideline-directed monitoring and management practices in the real world in patients with stage 3 CKD without a recorded diagnosis code. METHODS: REVEAL-CKD (NCT04847531) is a multinational, observational study of patients with stage 3 CKD. Eligible patients had ≥2 consecutive estimated glomerular filtration rate (eGFR) measurements indicative of stage 3 CKD recorded >90 and ≤730 days apart, lacked an International Classification of Diseases 9/10 diagnosis code corresponding to CKD any time before and up to 6 months after the second eGFR measurement. Testing of key measures of care quality were assessed. RESULTS: The study included 435,971 patients from 9 countries. In all countries, the prevalence of urinary albumin-creatinine ratio and albuminuria testing was low. Angiotensin-converting enzyme inhibitor, angiotensin receptor blocker and statin prescriptions were highly variable, and sodium-glucose cotransporter-2 inhibitor prescriptions remained below 21%. Blood pressure measurements were recorded in 20.2%-89.9% of patients. CONCLUSIONS: Overall, a large proportion of patients with evidence of stage 3 CKD did not receive recommended, guideline-directed monitoring and management. The variability in standard of care among countries demonstrates a clear opportunity to improve monitoring and management of these patients, most likely improving long-term outcomes.

DCRM 2.0: Multispecialty practice recommendations for the management of diabetes, cardiorenal, and metabolic diseases.

The spectrum of cardiorenal and metabolic diseases comprises many disorders, including obesity, type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), dyslipidemias, hypertension, and associated comorbidities such as pulmonary diseases and metabolism dysfunction-associated steatotic liver disease and metabolism dysfunction-associated steatohepatitis (MASLD and MASH, respectively, formerly known as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis [NAFLD and NASH]). Because cardiorenal and metabolic diseases share pathophysiologic pathways, two or more are often present in the same individual. Findings from recent outcome trials have demonstrated benefits of various treatments across a range of conditions, suggesting a need for practice recommendations that will guide clinicians to better manage complex conditions involving diabetes, cardiorenal, and/or metabolic (DCRM) diseases. To meet this need, we formed an international volunteer task force comprising leading cardiologists, nephrologists, endocrinologists, and primary care physicians to develop the DCRM 2.0 Practice Recommendations, an updated and expanded revision of a previously published multispecialty consensus on the comprehensive management of persons living with DCRM. The recommendations are presented as 22 separate graphics covering the essentials of management to improve general health, control cardiorenal risk factors, and manage cardiorenal and metabolic comorbidities, leading to improved patient outcomes.

Patient and Clinician Perspectives: To Create a Better Future for Chronic Kidney Disease, We Need to Talk About Our Kidneys.

Chronic kidney disease (CKD) affects more than one in ten people worldwide. However, results from the REVEAL-CKD study suggest that it is often not diagnosed. Many patients are therefore unaware that they have CKD, putting them at increased risk of disease progression and complications. Empowering patients with knowledge about CKD will allow them to become active participants in their own care, driving improvements in diagnosis rates and changing patient outcomes for the better. In this article, we provide patient and clinician perspectives on the importance of early CKD diagnosis and management. We present an overview of the tests commonly used to diagnose CKD in clinical practice, as well as actionable suggestions for patients, clinicians, and health policymakers that could help improve disease detection and treatment. Navdeep Tangri, a nephrologist and epidemiologist at the University of Manitoba, and Jane DeMeis, a patient living with chronic kidney disease, discuss how results from the REVEAL-CKD study highlight the need for change to improve management of chronic kidney disease. Video Abstract (MP4 141866 KB).

Patient Management and Clinical Outcomes Associated with a Recorded Diagnosis of Stage 3 Chronic Kidney Disease: The REVEAL-CKD Study.

INTRODUCTION: Guidelines for the treatment of chronic kidney disease (CKD) recommend early intervention and management to slow disease progression. However, associations between diagnosis and CKD progression are not fully understood. METHODS: REVEAL-CKD (NCT04847531) is a retrospective observational study of patients with stage 3 CKD. Data were extracted from the US TriNetX database. Eligible patients had two consecutive estimated glomerular filtration rate (eGFR) measurements indicative of stage 3 CKD (≥ 30 and < 60 ml/min/1.73 m2) recorded 91-730 days apart from 2015 to 2020. Diagnosed patients were included if their first CKD diagnosis code was recorded at least 6 months after their second qualifying eGFR measurement. We assessed CKD management and monitoring practices for the 180 days before and after CKD diagnosis, annual eGFR decline in the 2 years before and after CKD diagnosis, and associations between diagnostic delay and post-diagnosis event rates. RESULTS: The study included 26,851 patients. After diagnosis, we observed significant increases in the prescribing rate of guideline-recommended medications such as angiotensin-converting enzyme inhibitors (rate ratio [95% confidence interval]: 1.87 [1.82, 1.93]), angiotensin receptor blockers (1.91 [1.85, 1.97]) and mineralocorticoid receptor antagonists (2.23 [2.13, 2.34]). Annual eGFR decline was significantly reduced following a CKD diagnosis, from 3.20 ml/min/1.73 m2 before diagnosis to 0.74 ml/min/1.73 m2 after diagnosis. Delayed diagnosis (by 1-year increments) was associated with elevated risk of CKD progression to stage 4/5 (1.40 [1.31-1.49]), kidney failure (hazard ratio [95% confidence interval]: 1.63 [1.23-2.18]) and the composite of myocardial infarction, stroke and hospitalization for heart failure (1.08 [1.04-1.13]). CONCLUSIONS: A recorded CKD diagnosis was associated with significant improvements in CKD management and monitoring practices and attenuated eGFR decline. Recorded diagnosis of stage 3 CKD is an important first step to reduce the risk of disease progression and minimize adverse clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04847531.

Chronic kidney disease (CKD) is a long-term condition in which the function of the kidneys is reduced. Kidney function is monitored using a measurement called the estimated glomerular filtration rate. CKD can be separated into stages of severity, ranging from 1 (mild) to 5 (severe), using estimated glomerular filtration rate. Mild to moderate CKD (stages 1­3) is difficult to diagnose because there are usually no symptoms. In this study from the REVEAL-CKD programme, we looked at the effects of having undiagnosed stage 3 (moderate) CKD and examined how a CKD diagnosis affects disease management and worsening of the condition. Using a database of medical records for patients in the USA called TriNetX, we looked at data from over 26,000 patients with stage 3 CKD who were identified using estimated glomerular filtration rate measurements. We found that healthcare teams prescribed significantly more guideline-recommended medications and did more clinical monitoring in the 180 days after a CKD diagnosis than they did before the diagnosis. Additionally, the rate of decline in kidney function slowed after a CKD diagnosis. Delaying diagnosis by 1 year increased the risk of deterioration of the condition by 40%, the risk of needing a kidney transplant or long-term dialysis treatment by 63% and the risk of major heart and blood vessel diseases (known as cardiovascular events) by 8%. Our findings suggest that diagnosis of stage 3 CKD is an important first step to reduce the risk of the disease worsening and other complications. Video Abstract (MP4 82773 KB).

Prevalence of undiagnosed stage 3 chronic kidney disease in France, Germany, Italy, Japan and the USA: results from the multinational observational REVEAL-CKD study.

OBJECTIVES: REVEAL-CKD aims to estimate the prevalence of, and factors associated with, undiagnosed stage 3 chronic kidney disease (CKD). DESIGN: Multinational, observational study. SETTING: Data from six country-specific electronic medical records and/or insurance claims databases from five countries (France, Germany, Italy, Japan and the USA [two databases]). PARTICIPANTS: Eligible participants (≥18 years old) had ≥2 consecutive estimated glomerular filtration rate (eGFR) measurements (calculated from serum creatinine values, sex and age) taken from 2015 onwards that were indicative of stage 3 CKD (≥30 and <60 mL/min/1.73 m2). Undiagnosed cases lacked an International Classification of Diseases 9/10 diagnosis code for CKD (any stage) any time before, and up to 6 months after, the second qualifying eGFR measurement (study index). MAIN OUTCOME MEASURES: The primary outcome was point prevalence of undiagnosed stage 3 CKD. Time to diagnosis was assessed using the Kaplan-Meier approach. Factors associated with lacking a CKD diagnosis and risk of diagnostic delay were assessed using logistic regression adjusted for baseline covariates. RESULTS: The prevalence of undiagnosed stage 3 CKD was 95.5% (19 120/20 012 patients) in France, 84.3% (22 557/26 767) in Germany, 77.0% (50 547/65 676) in Italy, 92.1% (83 693/90 902) in Japan, 61.6% (13 845/22 470) in the US Explorys Linked Claims and Electronic Medical Records Data database and 64.3% (161 254/250 879) in the US TriNetX database. The prevalence of undiagnosed CKD increased with age. Factors associated with undiagnosed CKD were female sex (vs male, range of odds ratios across countries: 1.29-1.77), stage 3a CKD (vs 3b, 1.81-3.66), no medical history (vs a history) of diabetes (1.26-2.77) or hypertension (1.35-1.78). CONCLUSIONS: There are substantial opportunities to improve stage 3 CKD diagnosis, particularly in female patients and older patients. The low diagnosis rates in patients with comorbidities that put them at risk of disease progression and complications require attention. TRIAL REGISTRATION: NCT04847531.

Efficacy and Safety of Tirzepatide in Adults With Type 2 Diabetes: A Perspective for Primary Care Providers.

This article reviews the efficacy and safety data of tirzepatide, a once-weekly, novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 (GLP-1) receptor agonist approved in the United States, the European Union, and other regions for the treatment of type 2 diabetes. All doses of tirzepatide demonstrated superiority in reducing A1C and body weight from baseline versus placebo or active comparators. The safety profile of tirzepatide was consistent with that of the GLP-1 receptor agonist class, with mild to moderate and transient gastrointestinal side effects being the most common adverse events. With clinically and statistically significant reductions in A1C and body weight without increased risk of hypoglycemia in various populations, tirzepatide has demonstrated potential as a first-in-class treatment option for many people with type 2 diabetes.

Living with Type 2 Diabetes: Podcast of a Patient-Physician Discussion.

For patients with type 2 diabetes (T2D), the journey to diagnosis may not be straightforward. Patients can present with one of many diabetic complications before a diagnosis of T2D is made. These include heart disease and chronic kidney disease, in addition to cerebrovascular disease, peripheral vascular disease, retinopathy, and neuropathies, all of which can be asymptomatic in the early stages. In their clinical guidelines on standards of care in diabetes, the American Diabetes Association recommends regular screening for conditions such as kidney disease in patients with T2D. Furthermore, the frequent coexistence of diabetes and cardiorenal and/or metabolic conditions often requires a holistic approach to patient management, with specialists from multiple disciplines, including cardiologists, nephrologists, endocrinologists, and primary care physicians, working together. In addition to the use of pharmacological therapies, which can improve prognosis, the management of T2D should include attention to patient self-care, including appropriate dietary changes, consideration of continuous glucose monitoring, and advice on physical exercise. In this podcast, a patient and a clinician discuss a lived experience of the diagnosis of T2D, and the importance of patient education for understanding and managing T2D and its complications. The discussion highlights the central role of the Certified Diabetes Care and Education Specialist, and the role of ongoing emotional support in managing life with T2D, including patient education through reputable online resources and peer support groups. Podcast video with Pamela Kushner (PK) and Anne Dalin (AD) (MP4 92088 KB).

Early intervention and intensive management of patients with diabetes, cardiorenal, and metabolic diseases.

Increasing rates of obesity and diabetes have driven corresponding increases in related cardiorenal and metabolic diseases. In many patients, these conditions occur together, further increasing morbidity and mortality risks to the individual. Yet all too often, the risk factors for these disorders are not addressed promptly in clinical practice, leading to irreversible pathologic progression. To address this gap, we convened a Task Force of experts in cardiology, nephrology, endocrinology, and primary care to develop recommendations for early identification and intervention in obesity, diabetes, and other cardiorenal and metabolic diseases. The recommendations include screening and diagnosis, early interventions with lifestyle, and when and how to implement medical therapies. These recommendations are organized into primary and secondary prevention along the continuum from obesity through the metabolic syndrome, prediabetes, diabetes, hypertension, dyslipidemia, nonalcoholic fatty liver disease (NAFLD), atherosclerotic cardiovascular disease (ASCVD) and atrial fibrillation, chronic kidney disease (CKD), and heart failure (HF). The goal of early and intensive intervention is primary prevention of comorbidities or secondary prevention to decrease further worsening of disease and reduce morbidity and mortality. These efforts will reduce clinical inertia and may improve patients' well-being and adherence.

Role of Primary Care Clinicians in the Management of Patients With Type 2 Diabetes and Cardiorenal Diseases.

Individuals with type 2 diabetes are at increased risk of both renal and cardiovascular events. The convergence of type 2 diabetes, chronic kidney disease, and cardiovascular disease, including heart failure, requires management by a multidisciplinary health care team. Primary care clinicians are likely to be the first and most frequent point of contact for individuals with type 2 diabetes who are at high risk of cardiorenal disease and therefore play a pivotal role in early diagnosis, establishment of effective treatment strategies, and coordination of care. This article presents a clinical perspective with multidisciplinary collaboration on a patient case representative of those seen in routine clinical practice. The authors assess reasons why patients may not receive evidence-based care and identify opportunities to initiate therapies that reduce cardiovascular and renal events in the primary care setting.

The use of non-steroidal anti-inflammatory drugs (NSAIDs) in COVID-19.

Early in the COVID-19 pandemic, anecdotal reports emerged suggesting non-steroidal anti-inflammatory drugs (NSAIDs) may increase susceptibility to infection and adversely impact clinical outcomes. This narrative literature review (March 2020-July 2021) attempted to clarify the relationship between NSAID use and COVID-19 outcomes related to disease susceptibility or severity. Twenty-four relevant publications (covering 25 studies) reporting original research data were identified; all were observational cohort studies, and eight were described as retrospective. Overall, these studies are consistent in showing that NSAIDs neither increase the likelihood of SARS-CoV-2 infection nor worsen outcomes in patients with COVID-19. This is reflected in current recommendations from major public health authorities across the world, which support NSAID use for analgesic or antipyretic treatment during COVID-19. Thus, there is no basis on which to restrict or prohibit use of these drugs by consumers or patients to manage their health conditions and symptoms during the pandemic.

Investigating the global prevalence and consequences of undiagnosed stage 3 chronic kidney disease: methods and rationale for the REVEAL-CKD study.

Background: Timely diagnosis and treatment of stage 3 chronic kidney disease (CKD) can prevent further loss of kidney function and progression to kidney failure. However, contemporary data on the global prevalence of undiagnosed stage 3 CKD are scarce. REVEAL-CKD is a multinational, multifocal and observational study aiming to provide insights into undiagnosed stage 3 CKD in a large population. Methods: Patients (aged ≥18 years) with data in selected secondary databases from 11 countries will be included if they have at least two estimated glomerular filtration rate (eGFR) measurements from 2015 onwards that are ≥30 and <60 mL/min/1.73 m2, recorded >90 and ≤730 days apart. Undiagnosed cases are those without an International Classification of Diseases 9/10 diagnosis code for CKD (any stage) any time before and up to 6 months after the second qualifying eGFR measurement. Time to diagnosis will be assessed using a Kaplan-Meier approach; patient characteristics associated with undiagnosed CKD will be assessed using adjusted logistical regression analyses. Results: REVEAL-CKD will assess the point prevalence of undiagnosed stage 3 CKD and time to CKD diagnosis in initially undiagnosed cases overall and in individual countries. Trends in undiagnosed CKD prevalence by calendar year will be assessed. Patient characteristics, healthcare resource utilization, adverse clinical outcomes, and CKD management and monitoring practices in patients with versus without a CKD diagnosis will be compared. Conclusions: REVEAL-CKD will increase awareness of the global clinical and economic burden of undiagnosed stage 3 CKD and provide valuable insights to inform clinical practice and policy changes.

DCRM Multispecialty Practice Recommendations for the management of diabetes, cardiorenal, and metabolic diseases.

Type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF)-along with their associated risk factors-have overlapping etiologies, and two or more of these conditions frequently occur in the same patient. Many recent cardiovascular outcome trials (CVOTs) have demonstrated the benefits of agents originally developed to control T2D, ASCVD, or CKD risk factors, and these agents have transcended their primary indications to confer benefits across a range of conditions. This evolution in CVOT evidence calls for practice recommendations that are not constrained by a single discipline to help clinicians manage patients with complex conditions involving diabetes, cardiorenal, and/or metabolic (DCRM) diseases. The ultimate goal for these recommendations is to be comprehensive yet succinct and easy to follow by the nonexpert-whether a specialist or a primary care clinician. To meet this need, we formed a volunteer task force comprising leading cardiologists, nephrologists, endocrinologists, and primary care physicians to develop the DCRM Practice Recommendations, a multispecialty consensus on the comprehensive management of the patient with complicated metabolic disease. The task force recommendations are based on strong evidence and incorporate practical guidance that is clinically relevant and simple to implement, with the aim of improving outcomes in patients with DCRM. The recommendations are presented as 18 separate graphics covering lifestyle therapy, patient self-management education, technology for DCRM management, prediabetes, cognitive dysfunction, vaccinations, clinical tests, lipids, hypertension, anticoagulation and antiplatelet therapy, antihyperglycemic therapy, hypoglycemia, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), ASCVD, HF, CKD, and comorbid HF and CKD, as well as a graphical summary of medications used for DCRM.

Global survey investigating causes of treatment inertia in type 2 diabetes cardiorenal risk management.

AIM: To explore reasons behind treatment inertia in current approaches to early cardiorenal risk management in type 2 diabetes (T2D). METHODS: A global, web-based, quantitative panel survey of primary care physicians (PCPs) and primary care diabetes specialists treating people living with T2D. The questions covered current management of T2D, particularly the use of sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors as second-/third-line therapies. RESULTS: Of 1677 respondents from 18 countries who completed the survey, 73.4% were responsible for second-/third-line therapy initiation. Two thirds had modified treatment decisions based on recent cardiovascular outcomes trials (CVOTs). Respondents cited restricted access to therapies and limits on regular appointments as the greatest barriers to second-/third-line therapy prescription. Although 81.6% agreed that early intensification to second-/third-line therapies is associated with clinical benefits, 46.1% of respondents still reserve these for later lines of therapy, and 23.8% would not consider changing therapeutic approach in patients with well-controlled T2D but increasing cardiovascular risk. CONCLUSIONS: Substantial barriers still prevent optimization of primary setting T2D patient care. Education programs which enable PCPs to translate CVOT evidence into clinical benefits for patients with T2D could address many of the remaining knowledge gaps identified.

The Changing Landscape of Glycemic Targets: Focus on Continuous Glucose Monitoring.

Continuous glucose monitoring (CGM) provides comprehensive assessment of daily glucose measurements for patients with diabetes and can reveal high and low blood glucose values that may occur even when a patient's A1C is adequately controlled. Among the measures captured by CGM, the percentage of time in the target glycemic range, or "time in range" (typically 70-180 mg/dL), has emerged as one of the strongest indicators of good glycemic control. This review examines the shift to using CGM to assess glycemic control and guide diabetes treatment decisions, with a focus on time in range as the key metric of glycemic control.

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.

Hypertriglyceridemia: the importance of identifying patients at risk.

This review aims to explain risk factors, consequences, and management strategies recommended for patients with hypertriglyceridemia. A search of PubMed was performed: 'Hypertriglyceridemia'[Majr], limited to English-language and published in the 5 years up to April 2016. Abstracts of the 680 results were screened for inclusion. Reference lists of publications included were also screened for inclusion. Approximately 25% of the United States population has elevated (≥150 mg/dL) triglycerides (TG) putting them at an increased risk of cardiovascular disease, non-alcoholic fatty liver disease, and pancreatitis. Risk factors for hypertriglyceridemia include genetics, lifestyle and diet, renal disease, endocrine disorders, and certain medications. Guidelines recommend that all patients with hypertriglyceridemia are advised on lifestyle modification to reduce TG to <150 mg/dL; a reduction in body weight of 5-10% can reduce TG by approximately 20%. For patients with TG <400 mg/dL, the primary goal is to reduce low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol, with most guidelines recommending statin therapy. When TG is ≥500 mg/dL the primary goal is to reduce TG levels to lower the risk of pancreatitis. Statin therapy (if LDL-C is elevated) in combination with a fibrate, or long-chain omega-3 fatty acid may be required. The Food and Drug Administration withdrew approval for niacin and some fibrates in combination with statins in April 2016 citing unfavorable benefit-risk profiles. With the increasing incidence of associated conditions (e.g. obesity, metabolic syndrome, and type 2 diabetes mellitus), it is likely that primary care physicians will encounter more patients with hypertriglyceridemia.

Benefits/risks of sodium-glucose co-transporter 2 inhibitor canagliflozin in women for the treatment of Type 2 diabetes.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, such as canagliflozin, are used in patients with Type 2 diabetes mellitus (T2DM). In clinical studies, canagliflozin significantly reduced A1C, bodyweight and blood pressure, and was generally well tolerated with no increased risk of hypoglycemia. Most common adverse effects observed were genital mycotic infections and urinary tract infections, and increased urination. Approximately 10% of women treated with canagliflozin experienced a genital mycotic infection compared with 3% treated with placebo; those with a prior history were at greater risk. Approximately 9% of women treated with canagliflozin reported a urinary tract infection compared with 7% treated with placebo. Most adverse events were considered mild to moderate in intensity and responded to standard therapy. Treatment with canagliflozin was effective and generally well tolerated in both women (and men) with T2DM.

Management of Daily Glycemic Fluctuations in Patients With Type 2 Diabetes.

Traditional measures of overall glucose control, such as glycated hemoglobin (A1C), may not fully capture short-term, rapid changes in blood glucose. With the availability of multiple options to control A1C, glycemic fluctuations have emerged as an additional therapeutic goal for the management of type 2 diabetes (T2D).

User's guide to mechanism of action and clinical use of GLP-1 receptor agonists.

Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are injectable glucose-lowering medications approved for the treatment of adult patients with type 2 diabetes mellitus (T2DM). This article provides practical information to guide primary care physicians on the use of GLP-1RAs in patients with T2DM. Two short-acting (once- or twice-daily administration; exenatide and liraglutide) and three long-acting (weekly administration; albiglutide, dulaglutide and exenatide) GLP-1RAs are currently approved in the US. These drugs provide levels of GLP-1 receptor agonism many times that of endogenous GLP-1. The GLP-1RAs have been shown to significantly improve glycemic parameters and reduce body weight. These agents work by activating GLP-1 receptors in the pancreas, which leads to enhanced insulin release and reduced glucagon release-responses that are both glucose-dependent-with a consequent low risk for hypoglycemia. Effects on GLP-1 receptors in the CNS and the gastrointestinal tract cause reduced appetite and delayed glucose absorption due to slower gastric emptying. The most common adverse effects are gastrointestinal, which are transient and less common with the long-acting drugs. GLP-1RAs are recommended as second-line therapy in combination with metformin, sulfonylureas, thiazolidinediones or basal insulin, providing a means of enhancing glucose control while offsetting the weight gain associated with insulin and some oral agents. GLP-1RAs represent a useful tool that the primary care physician can use to help patients with T2DM achieve their therapeutic goals.