Potential delayed and/or missed STI diagnoses among outpatients presenting with lower genitourinary tract symptoms: a real-world database study.

OBJECTIVES: Sexually transmitted infection (STI) diagnosis is complicated as these infections can present with lower genitourinary tract symptoms (LGUTS) that overlap with other disorders, i.e. urinary tract infections (UTIs). The study's objective was to determine potential missed STI diagnoses from patients presenting with LGUTS in the US between January 2010 and December 2019. METHODS: The de-identified insurance claims data from the IBM® MarketScan® Research Databases were collected from patients (14-64 years old) who presented with LGUTS, which could be caused by an STI. A 'GAP' cohort was created, consisting of episodes with potentially delayed STI (Chlamydia trachomatis [CT]/Neisseria gonorrhoeae [NG]) treatment. The intention was to capture episodes where an STI was not initially suspected. Four subgroups were defined depending on the treatment received (fluoroquinolone; azithromycin and/or doxycycline; cephalosporins; gentamicin and azithromycin). RESULTS: The GAP cohort consisted of 833,574 LGUTS episodes from the original cohort (23,537,812 episodes). Post-index CT/NG testing was carried out for 4.6% and 5.4% of the episodes from men and women, respectively. There were ≥2 return visits for 16.1% and 15.8% of the episodes from men and women, respectively. A substantial percentage of episodes from men (52.1%) and women (68.3%) were diagnosed with a UTI and/or acute cystitis at the index prior to receiving post-index STI treatment. Other top conditions diagnosed at index for men were dysuria (25.8% of the episodes), orchitis/epididymitis (14.3% of the episodes), and acute prostatitis (10.1% of the episodes), and for women were dysuria (24.2% of the episodes), vaginitis/vulvitis/vulvovaginitis (11.7% of the episodes), and cervicitis (3.3% of the episodes). CONCLUSION: These findings highlight delayed STI antibiotic treatment and low rates of CT/NG testing, suggesting late STI consideration and suboptimal diagnosis. Additionally, our study illustrates the importance of accurately diagnosing and treating STIs in patients with LGUTS and associated conditions, to avoid antibiotic misuse and complications from delayed administration of appropriate treatment.

Outpatient sexually transmitted infection testing and treatment patterns in the United States: a real-world database study.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most common notifiable sexually transmitted infections (STIs) in the United States. Because symptoms of these infections often overlap with other urogenital infections, misdiagnosis and incorrect treatment can occur unless appropriate STI diagnostic testing is performed in clinical settings. The objective of this study was to describe STI diagnostic testing and antimicrobial treatment patterns and trends among adolescent and adult men and women with lower genitourinary tract symptoms (LGUTS). METHODS: We analyzed insurance claims data from the IBM® MarketScan® Research Databases. Patients included were between 14 and 64 years old with LGUTS as determined by selected International Classification of Diseases codes between January 2010 and December 2019. Testing of STIs and relevant drug claims were captured, and distribution of testing patterns and drug claims were described. RESULTS: In total, 23,537,812 episodes with LGUTS (87.4% from women; 12.6% from men) were analyzed from 12,341,154 patients. CT/NG testing occurred in only 17.6% of all episodes. For episodes where patients received treatment within 2 weeks of the visit date, 89.3% received treatment within the first 3 days (likely indicating presumptive treatment), and 77.7% received it on the first day. For women with pelvic inflammatory disease and men with orchitis/epididymitis and acute prostatitis, ≤ 15% received CT/NG testing, and around one-half received antibiotic treatment within 3 days. CONCLUSIONS: Our study revealed low CT/NG testing rates, even in patients diagnosed with complications commonly associated with these STIs, along with high levels of potentially inappropriate presumptive treatment. This highlights the need for timely and accurate STI diagnosis in patients with LGUTS to inform appropriate treatment recommendations.

Efficacy and safety of tanezumab, NSAIDs, and placebo in patients with moderate to severe hip or knee osteoarthritis and a history of depression, anxiety, or insomnia: post-hoc analysis of phase 3 trials.

Objective: Treatment outcomes for chronic pain can be poor in patients with depression, anxiety, or insomnia. This analysis evaluated the efficacy and safety of subcutaneous tanezumab, nonsteroidal anti-inflammatory drugs (NSAIDs), and placebo in patients with osteoarthritis (OA) and a history of these conditions using data from three phase 3 studies.Methods: A post-hoc analysis of data from two pooled placebo-controlled studies and one NSAID-controlled study of subcutaneous tanezumab. All patients had moderate to severe knee or hip OA that was inadequately controlled with standard-of-care analgesics. Efficacy outcomes were least-squares mean change from baseline to Week 16 in Western Ontario McMaster Universities OA Index (WOMAC) Pain, WOMAC Physical Function, Patient's global assessment of OA, and EQ-5D-5L scores. Results were summarized for patients with and without a history of depression, anxiety, or insomnia at baseline.Results: 1545 patients were treated in the pooled placebo-controlled studies (history of depression, 12%; anxiety, 8%; insomnia, 10%; any, 23%) and 2996 in the NSAID-controlled study (16%, 11%, 13%, 28%, respectively). In groups with positive histories, 38-80% took antidepressant or anxiolytic medications at baseline. Within treatments, largely similar improvements in efficacy outcomes were observed in patients with and without a history of depression, anxiety, or insomnia; the types of treatment-emergent adverse events were similar.Conclusions: Patients with OA and a history of depression, anxiety, or insomnia did not appear to experience reduced efficacy outcomes or an altered safety profile in response to tanezumab or NSAID treatment as compared with those without. NCT02697773; NCT02709486; NCT02528188.

Primary Care of Adult Patients After Stroke: A Scientific Statement From the American Heart Association/American Stroke Association.

Primary care teams provide the majority of poststroke care. When optimally configured, these teams provide patient-centered care to prevent recurrent stroke, maximize function, prevent late complications, and optimize quality of life. Patient-centered primary care after stroke begins with establishing the foundation for poststroke management while engaging caregivers and family members in support of the patient. Screening for complications (eg, depression, cognitive impairment, and fall risk) and unmet needs is both a short-term and long-term component of poststroke care. Patients with ongoing functional impairments may benefit from referral to appropriate services. Ongoing care consists of managing risk factors such as high blood pressure, atrial fibrillation, diabetes, carotid stenosis, and dyslipidemia. Recommendations to reduce risk of recurrent stroke also include lifestyle modifications such as healthy diet and exercise. At the system level, primary care practices can use quality improvement strategies and available resources to enhance the delivery of evidence-based care and optimize outcomes.

Practical guidance on the initiation, titration, and switching of basal insulins: a narrative review for primary care.

Many patients with type 2 diabetes will ultimately require the inclusion of basal insulin in their treatment regimen. Since most people with type 2 diabetes are managed in the community, it is important that primary care providers understand and correctly manage the initiation and titration of basal insulins, and help patients to self-manage insulin injections. Newer, long-acting basal insulins provide greater stability and flexibility than older preparations and improved delivery systems. Basal insulin is usually initiated at a conservative dose of 10 units/day or 0.1-0.2 units/kg/day, then titrated thereafter over several weeks or months, based on patients' self-measured fasting plasma glucose, to achieve an individualized target (usually 80-130 mg/dL). Through a shared decision-making process, confirmation of appropriate goals and titration methods should be established, including provisions for events that might alter scheduled titration (e.g. travel, dietary change, illness, hospitalization, etc.). Although switching between basal insulins is usually easily accomplished, pharmacokinetic and pharmacodynamic differences between formulations require clinicians to provide explicit guidance to patients. Basal insulin is effective long-term, but overbasalization (continuing to escalate dose without a meaningful reduction in fasting plasma glucose) should be avoided.Key messagesPrimary care providers often initiate basal insulin for people with type 2 diabetes.Basal insulin is recommended to be initiated at 10 units/day or 0.1-0.2 units/kg/day, and doses must be titrated to agreed fasting plasma glucose goals, usually 80-130 mg/dL. A simple rule is to gradually increase the initial dose by 1 unit per day (NPH, insulin detemir, and glargine 100 units/mL) or 2-4 units once or twice per week (NPH, insulin detemir, glargine 100 and 300 units/mL, and degludec) until FPG levels remain consistently within the target range. If warranted, switching between basal insulins can be done using simple regimens.The dose of basal insulin should be increased as required up to approximately 0.5-1.0 units/kg/day in some cases. Overbasalization (continuing to escalate dose without a meaningful reduction in fasting plasma glucose) is not recommended; rather re-evaluation of individual therapy, including consideration of more concentrated basal insulin preparations and/or short-acting prandial insulin as well as other glucose-lowering therapies, is suggested.

Open-Label Adhesion Performance Studies of a New Lidocaine Topical System 1.8% versus Lidocaine Patches 5% and Lidocaine Medicated Plaster 5% in Healthy Subjects.

PURPOSE: The primary objective was to evaluate adhesion performance of the lidocaine topical system 1.8% for 12 hours in healthy human subjects in three studies: as a single product (Study 1) and versus other lidocaine topical products (lidocaine patch 5% and lidocaine medicated plaster 5% [Study 2] and generic lidocaine patch 5% [Study 3]). Safety of the lidocaine topical system 1.8%, with a skin irritation focus, was a secondary objective. PATIENTS AND METHODS: All three studies were open-label, randomized, Phase 1 adhesion performance studies in healthy adult volunteers (N=125). Lidocaine topical products were applied for 12 hours per test, per study arm. Adhesion of all test products was scored at 0, 3, 6, 9, and 12 hours post-application. Skin irritation was scored after product removal or when a product detached. RESULTS: Overall, the majority (≥75%) of subjects treated with the lidocaine topical system 1.8% demonstrated ≥90% adhesion (FDA adhesion score 0) throughout the 12-hour administration period versus 13.6% of subjects treated with lidocaine patch 5%, 15.9% of subjects treated with lidocaine medicated plaster 5%, and 0% of subjects treated with the generic lidocaine patch 5%. There were no complete detachments with the lidocaine topical system 1.8%, whereas 4.5% of lidocaine patch 5% and lidocaine medicated plaster 5% detached, and 29% of generic lidocaine patch 5% detached. Minimal skin irritation was observed with each lidocaine topical product. CONCLUSION: Across three studies, lidocaine topical system 1.8% demonstrated superior adhesion performance versus the three other products tested. Skin irritation was minimal across products and studies. CLINICALTRIALSGOV: NCT04312750, NCT04320173, NCT04319926.

Management of irritable bowel syndrome with diarrhea: focus on eluxadoline.

OBJECTIVE: We sought to summarize current recommendations for the diagnosis of diarrhea-predominant irritable bowel syndrome (IBS-D) and describe available management options, highlighting a newer US Food and Drug Administration (FDA)-approved agent, eluxadoline. METHODS: Literature on IBS-D was assessed up to January 2020 using PubMed, with key search terms including "IBS-D diagnosis", "IBS-D management", and "eluxadoline". RESULTS: IBS is a common gastrointestinal disorder affecting up to 14% of US adults and is particularly prevalent in women and those aged under 50. Symptoms include abdominal pain associated with altered bowel habits (i.e. diarrhea and/or constipation subtyped based on the predominant stool pattern). As IBS-D is challenging to manage with varying symptom severity, effective treatment requires a personalized management approach. Evidence-based therapeutic options endorsed by the American Gastroenterological Association and the American College of Gastroenterology can be used to effectively guide treatment. Dietary and lifestyle modifications, including adequate hydration, reducing caffeine and alcohol intake, and increasing soluble fiber intake may lead to symptom improvement. Over-the-counter medications such as loperamide are frequently recommended and may improve stool frequency and rectal urgency; however, for the outcome of abdominal pain, mixed results have been observed. Several off-label prescription medications are useful in IBS-D management, including tricyclic antidepressants, bile acid sequestrants, and antispasmodics. Three prescription medications have been approved by the FDA for IBS-D: alosetron, eluxadoline, and rifaximin. CONCLUSIONS: IBS-D can be effectively managed in the primary care setting in the absence of alarm features. Benefits and risks of pharmacologic interventions should be weighed during treatment selection.

Are residents receiving the training needed within their residency programs to optimally manage patients with diabetes?

Objective: Diabetes is a prevalent and growing problem in the United States (U.S.); primary care physicians need to be prepared to initiate and progressively advance treatment. The objective of this study was to understand how diabetes management is taught in U.S. Family Medicine (FM) and Internal Medicine (IM) residency programs.Methods: Invitations to complete an online survey were sent via postal mail to U.S. FM and IM residency programs in 2019.Results: Directors/associate directors from 68 FM residencies and 66 IM residencies completed the online survey out of 645 (10.5%) and 505 (13.1%) programs, respectively. Most respondents rated cardiovascular disease and risk management in diabetes as 'very important' (90%), but only about half (47%) did so for newer generation insulin analogs and 27% for digital health technologies. About two-thirds of programs cover non-insulin options for type 2 diabetes (66%) and types of insulin (63%) to a great extent, but only about one-third of programs cover social determinants of health (36%) and pre-diabetes (35%) to this degree. Many programs report plans to expand training on cardiovascular disease and diabetes (59%), but only 32% plan to expand training on digital technology for diabetes care. Lack of faculty time and competing priorities are cited as being the biggest barriers to expanding diabetes training.Conclusions: Our study found that the current U.S. FM and IM residency program diabetes curricula are dominantly oriented toward cardiovascular disease and 'traditional' insulins. A variety of training materials and resources could help overcome some of the current barriers to curriculum expansion of other important components of diabetes care that may help future physicians successfully manage diabetes with newer generation insulin and glucose monitoring technologies.Abbreviations: U.S: United States; PCP: Primary Care Physician; FM: Family Medicine; IM: Internal Medicine; CGM: Continuous Glucose Monitor; AAFP: American Academy of Family Physicians; ACGME: Accreditation Council for Graduate Medical Education; U/mL: units per milliliter; CME: Continuing Medical Education.

Structured Blood Glucose Monitoring in Primary Care: A Practical, Evidence-Based Approach.

Comprehensive care of diabetes requires satisfactory stewardship of an underutilized prescription in diabetes management: the prescription for structured blood glucose monitoring (BGM). Structured BGM is a recommended schedule of actionable blood glucose measurements taken at specific times with the intent of using the data for individualized patient education and therapeutic intervention. The utility of different BGM protocols is logically dictated by a patient's therapeutic regimen. This article reviews the prescription for structured BGM in the setting of intensive insulin, nonintensive basal insulin, and noninsulin treatment regimens. Evidence-based prescriptions of structured 5- to 7-point BGM profiles in diabetes provide essential information for productive clinician- and patient-directed therapeutic interventions. The effective implementation of structured BGM aids clinicians in achieving the desired goal of A1C reduction while bolstering patient education and empowering self-management.

Practical Guidance on Effective Basal Insulin Titration for Primary Care Providers.

IN BRIEF Basal insulin therapy is well established for glycemic control in patients with diabetes but often is not optimally implemented, leading to poor clinical outcomes and adherence. Primary care providers can and should work together with other members of the diabetes care team to allow for effective titration of basal insulin that involves patients and their caregivers. Adequate guidance and monitoring during the titration process can minimize some of the adverse effects caused by basal insulin administration, while improving glycemic control in a timely manner.

The Mediterranean Diet: Lost in Translation.

PURPOSE OF REVIEW: Despite substantive evidence documenting the efficacy of the Mediterranean diet to reduce cardiovascular events, underutilization is common. An overview of the data set supporting the role of the Mediterranean diet as confirmed in both observational and interventional trials should stimulate greater clinician interest in the diet. Additionally, the availability of patient-friendly tools that enable prompt and easy adoption of the Mediterranean diet, that are able to be used by clinicians who claim no special expertise in diet knowledge, should simplify the path to successful dietary change. RECENT FINDINGS: A large recently published (2018) prospective study of the Mediterranean diet for primary prevention of cardiovascular events confirmed that compared to control, Mediterranean diet is associated with reduced risk for cardiovascular events in high risk patients. Of the tools available to clinicians that might reduce cardiovascular risk, dietary intervention is the one least utilized. The evidence supports the value of dietary intervention with the Mediterranean diet, and methods to effectively employ it within the confines of typical office practice are readily at hand.

Safety and efficacy of a glucagon-like peptide-1 receptor agonist added to basal insulin therapy versus basal insulin with or without a rapid-acting insulin in patients with type 2 diabetes: results of a meta-analysis.

OBJECTIVE: To consolidate the evidence from randomized controlled trials evaluating the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as add-on to basal insulin therapy in type 2 diabetes (T2D) patients. RESEARCH DESIGN AND METHODS: We searched the EMBASE® and NCBI PubMed (Medline) databases and relevant congress abstracts for randomized controlled trials evaluating the efficacy and safety of GLP-1 RAs as add-on to basal insulin compared with basal insulin with or without rapid-acting insulin (RAI) through 23 May 2016. The pooled data were analyzed using a random-effects meta-analysis model. A subanalysis was performed for trials investigating basal insulin plus GLP-1 RAs versus basal insulin plus RAI. RESULTS: Of the 2617 retrieved records, 19 randomized controlled trials enrolling 7,053 patients with T2D were included. Compared with basal insulin ± RAI, reduction in glycated hemoglobin (HbA1c) from baseline (difference in means: -0.48% [95% confidence interval (CI), -0.67 to -0.30]; p < 0.0001) and weight loss (-2.60 kg [95% CI, -3.32 to -1.89]; p < 0.0001) were significantly greater with basal insulin plus GLP-1 RA. The subanalysis similarly showed significant results for change in HbA1c from baseline and for weight loss, as well as a significantly lower risk of symptomatic hypoglycemia in patients treated with basal insulin plus GLP-1 RA versus basal insulin plus RAI (odds ratio, 0.52 [95% CI, 0.42 to 0.64]; p < 0.0001). CONCLUSIONS: Addition of GLP-1 RA to basal insulin provided improved glycemic control, led to weight reduction and similar hypoglycemia rates versus an intensified insulin strategy; however, symptomatic hypoglycemia rates were significantly lower when compared with a basal insulin plus RAI.

The recommendations of a consensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension.

Neurogenic orthostatic hypotension (nOH) is common in patients with neurodegenerative disorders such as Parkinson's disease, multiple system atrophy, pure autonomic failure, dementia with Lewy bodies, and peripheral neuropathies including amyloid or diabetic neuropathy. Due to the frequency of nOH in the aging population, clinicians need to be well informed about its diagnosis and management. To date, studies of nOH have used different outcome measures and various methods of diagnosis, thereby preventing the generation of evidence-based guidelines to direct clinicians towards 'best practices' when treating patients with nOH and associated supine hypertension. To address these issues, the American Autonomic Society and the National Parkinson Foundation initiated a project to develop a statement of recommendations beginning with a consensus panel meeting in Boston on November 7, 2015, with continued communications and contributions to the recommendations through October of 2016. This paper summarizes the panel members' discussions held during the initial meeting along with continued deliberations among the panel members and provides essential recommendations based upon best available evidence as well as expert opinion for the (1) screening, (2) diagnosis, (3) treatment of nOH, and (4) diagnosis and treatment of associated supine hypertension.

Answers to Clinical Questions in the Primary Care Management of People with Obesity: Practice Redesign and Reimbursement.

Determining what treatment options the patient's insurance will cover and considering the patient's out-of-pocket costs are important actions to be taken while collaborating with the patient and other team members and during the development and implementation of the treatment plan. Reimbursement is available to PCPs for some obesity-related services.

Recognizing and minimizing hypoglycemia: The need for individualized care.

Hypoglycemia is a condition known to disrupt many everyday activities and is associated with increased risks of hospitalization, falls, motor vehicle accidents and mortality. Many patients with diabetes have an increased risk of hypoglycemia due to interventions targeting glycemic control. In these patients, hypoglycemia and fear of hypoglycemia may further reduce adherence to glucose-lowering regimens, contributing to the further aggravation of diabetes-related complications. Avoiding hypoglycemia should be one of the principal goals of any treatment strategies employing agents that can induce hypoglycemia in order to prevent the occurrence of associated symptoms and consequences. The education of patients and their families is an important feature of individualized management strategies in order to prevent, mitigate and treat hypoglycemic episodes. Patients with diabetes need to be made aware of how to recognize the signs of hypoglycemia and of the simple, highly effective steps that they can take to self-manage hypoglycemic episodes. Clinicians should be familiar with the risk factors for hypoglycemia, especially the profiles of the different classes of glucose-lowering medications such as the sulfonylureas and insulin. This article aims to review the risk factors for hypoglycemia and its implications for patients and healthcare systems, and provide practical advice for minimizing the risk of hypoglycemia and its consequences.

Diagnosing and treating neurogenic orthostatic hypotension in primary care.

In response to a change in posture from supine or sitting to standing, autonomic reflexes normally maintain blood pressure (BP) by selective increases in arteriovenous resistance and by increased cardiac output, ensuring continued perfusion of the central nervous system. In neurogenic orthostatic hypotension (NOH), inadequate vasoconstriction and cardiac output cause BP to drop excessively, resulting in inadequate perfusion, with predictable symptoms such as dizziness, lightheadedness and falls. The condition may represent a central failure of baroreceptor signals to modulate cardiovascular function, a peripheral failure of norepinephrine release from cardiovascular sympathetic nerve endings, or both. Symptomatic patients may benefit from both non-pharmacologic and pharmacologic interventions. Among the latter, two pressor agents have been approved by the US Food and Drug Administration: the sympathomimetic prodrug midodrine, approved in 1996 for symptomatic orthostatic hypotension, and the norepinephrine prodrug droxidopa, approved in 2014, which is indicated for the treatment of symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure (Parkinson's disease, multiple system atrophy and pure autonomic failure). A wide variety of off-label options also have been described (e.g. the synthetic mineralocorticoid fludrocortisone). Because pressor agents may promote supine hypertension, NOH management requires monitoring of supine BP and also lifestyle measures to minimize supine BP increases (e.g. head-of-bed elevation). However, NOH has been associated with cognitive impairment and increases a patient's risk of syncope and falls, with the potential for serious consequences. Hence, concerns about supine hypertension - for which the long-term prognosis in patients with NOH is yet to be established - must sometimes be balanced by the need to address a patient's immediate risks.

Hot Topics in Primary Care: Individualizing Pharmacologic Management of Irritable Bowel Syndrome.

Irritable bowel syndrome is a common gastrointestinal disorder with constipation, diarrhea, and mixed subtypes. The diagnosis is generally based on a detailed history utilizing the Rome III criteria. Alarm signals necessitate more extensive diagnostic evaluation. Nonpharmacologic options and over-the-counter remedies (e.g., loperamide) might not be supported by strong evidence, but are often chosen as initial treatment for their safety and tolerability. Psychological interventions may be beneficial. Newer pharmacologic agents such as alosetron, eluxadoline, linaclotide, lubiprostone, and rifaximin are supported by higher quality evidence than older agents such as antispasmodics and laxatives. Patients with IBS commonly report that clinicians offer insufficient empathy and validation of their symptoms. Physicians therefore should strive to improve communication methods that specifically provide such reassurance. Individualizing treatment based on patient values and preferences is essential.

A patient-centered approach to managing patients with type 2 diabetes.

Despite the availability of a number of therapeutic options, management of type 2 diabetes (T2DM) and hyperglycemia remains suboptimal. Evidence shows that physicians are not adequately individualizing incretin-based therapies as there is lack of clear understanding of the similarities and differences between various incretin-based therapies. Additionally, sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors, a very recent addition to the therapeutic armamentarium, are not adequately utilized in managing patients with T2DM due to a lack of awareness or an increased concern regarding their safety, efficacy, and the mechanism of action. Insulin therapy is also not initiated or intensified appropriately due to a lack of clear understanding on when to add and how to intensify them and, more importantly, due to fear of increasing the risk of hypoglycemia in patients. To address these gaps, in the first section of this educational activity, the expert faculty will review the current understanding of the risks associated with hypoglycemia-one of the main factors that limit the successful use of insulin therapy-and when to initiate insulin therapy, as well as the available data on the risk of hypoglycemia with emerging agents. The expert faculty will also provide practical strategies on how to minimize the risk of hypoglycemia in patients. In the second section, the expert faculty will highlight the differences between the various incretin-based therapies in addition to providing strategies for physicians to individualize their choice of incretin-based therapy. The expert faculty will also review the mechanism of action, safety, efficacy, and the appropriate place for this class of therapies in the treatment continuum. In the third section, the expert faculty will discuss the mechanism of action, safety, and efficacy of the currently available SGLT2 inhibitors as well as the appropriate use of these newer agents in T2DM management. This CME Multimedia Activity is also available through the Website of The American Journal of Medicine (www.amjmed.com). Click on the CME Multimedia Activity button in the navigation bar for full access. Or access: www.elseviercme.com/537.

Sodium glucose co-transporter 2 inhibitors and their mechanism for improving glycemia in patients with type 2 diabetes.

Most antihyperglycemic agents available for the treatment of type 2 diabetes mellitus (T2DM) have insulin-dependent mechanisms of action; that is, they either stimulate insulin production (sulfonylureas, glinides, incretin mimetics, dipeptidyl peptidase-4 inhibitors), improve insulin sensitivity (thiazolidinediones, biguanides), or directly augment endogenous insulin (basal and prandial insulins). As ß-cell function deteriorates, combination therapy is usually needed to effectively control glycemia. Moreover, some antihyperglycemic agents are associated with adverse effects, such as weight gain and hypoglycemia. A novel approach for treating T2DM is to inhibit renal glucose reabsorption through inhibition of sodium glucose co-transporter 2 (SGLT2), which is responsible for the majority of glucose reabsorption in the renal proximal tubule. By reducing the renal capacity to reabsorb filtered glucose, SGLT2 inhibitors increase excretion of excess glucose in urine, thereby decreasing plasma glucose concentration. Thus, although glucosuria is often viewed as an indicator of systemic hyperglycemia, this perception needs to be modified in patients treated with SGLT2 inhibitors where glucosuria is an indicator of the desired treatment effect. Currently, 2 SGLT2 inhibitors, canagliflozin and dapagliflozin, are approved in the United States for the treatment of patients with T2DM; other SGLT2 inhibitors are in various stages of clinical development. Clinical studies in patients with T2DM on a variety of background diabetes treatments have demonstrated the efficacy of canagliflozin and dapagliflozin in improving glycemic control and reducing body weight and blood pressure. Canagliflozin and dapagliflozin are generally well tolerated, with a low risk of hypoglycemia when not used in combination with insulin and/or sulfonylurea. Higher incidences of genital mycotic infections and adverse events related to osmotic diuresis and volume depletion were observed with both agents; they were generally mild or moderate and infrequently led to study discontinuation. Based on current evidence, SGLT2 inhibitors provide an important new treatment option for patients with T2DM.