SGLT2 inhibitors: a narrative review of efficacy and safety.

Type 2 diabetes mellitus (T2DM) is a cardio-renal-metabolic condition that is frequently associated with multiple comorbidities, including atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD). The sodium-glucose co-transporter-2 (SGLT2) inhibitors, which lower glycated hemoglobin, fasting and postprandial plasma glucose levels, body weight, and blood pressure, as well as reduce the risk of a range of cardiovascular and renal outcomes without increasing hypoglycaemic risk, have heralded a paradigm shift in the management of T2DM. These drugs are compatible with most other glucose-lowering agents and can be used in patients with a wide range of comorbid conditions, including ASCVD, HF, and CKD, and in those with estimated glomerular filtration rates as low as 30 mL/min/1.73 m2. However, there are misunderstandings surrounding the clinical implications of SGLT2 inhibitors' mechanism of action and concerns about the key adverse events with which this class of drugs has been associated. This narrative review summarizes the data that support the efficacy of SGLT2 inhibitors in reducing the risks of cardiovascular and renal outcomes in patients with T2DM and comorbid conditions and clarifies information relating to SGLT2 inhibitor-related adverse events.

The Phoenix Physician: defining a pathway toward leadership in patient-centered care.

Health care delivery has evolved in reaction to scientific and technological discoveries, emergent patient needs, and market forces. A current focus on patient-centered care has pointed to the need for the reallocation of resources to improve access to and delivery of efficient, cost-effective, quality care. In response to this need, primary care physicians will find themselves in a new role as team leader. The American College of Osteopathic Internists has developed the Phoenix Physician, a training program that will prepare primary care residents and practicing physicians for the changes in health care delivery and provide them with skills such as understanding the contributions of all team members (including an empowered and educated patient), evaluating and treating patients, and applying performance metrics and information technology to measure and improve patient care and satisfaction. Through the program, physicians will also develop personal leadership and communication skills.

Correlating patient-reported response to hydroxypropyl cellulose ophthalmic insert (LACRISERT®) therapy with clinical outcomes: tools for predicting response.

BACKGROUND/AIMS: To determine whether patient-reported improvement in symptoms of dry eye syndrome, activities of daily living, and other quality-of-life measures after treatment with hydroxypropyl cellulose ophthalmic inserts correlates significantly with physician assessment of clinical outcomes. METHODS: Patient registry of those treated for 1 month with inserts as monotherapy or in combination with existing treatments for moderate-to-severe dry eye syndrome. A total of 520 participants were enrolled. Of those, 418 patients completed the study. Results of this registry were evaluated and correlations were calculated to determine whether patient-reported symptoms, quality of life, and changes in disease severity based on the Ocular Surface Disease Index, and activities of daily living outcomes are predictive of physician assessment of clinical signs, symptoms, and adherence to therapy. RESULTS: Most patients reported overall improvement in their condition. Patient-reported improvements in the symptoms of dry eye syndrome and activities of daily living were significant predictors of physician assessment of compliance with insert therapy, improvement in symptoms and clinical signs, effectiveness of therapy, and acceptance of use as adjunctive therapy. CONCLUSIONS: Patient-reported symptoms and activities of daily living are predictors of patient compliance and treatment success with the use of inserts, as reported by treating physicians. The benefits were additive to the standard of care that was continued during the course of the study. These predictors, along with clinical diagnostic tests, can be used by eye care professionals to assess the efficacy of treatment for moderate-to-severe dry eye syndrome quickly and reliably.

Efficacy of hydroxypropyl cellulose ophthalmic inserts (LACRISERT) in subsets of patients with dry eye syndrome: findings from a patient registry.

PURPOSE: To determine acceptability and efficacy of hydroxypropyl cellulose ophthalmic inserts in patients with dry eye syndrome (DES) and additional comorbidities. DESIGN: A multicenter, 2-visit, open-label, 4-week registry study. PARTICIPANTS: Five hundred twenty patients were recruited to the intent-to-treat group. Four hundred eighteen patients completed the study including 86 contact lens wearers, 79 with cataract diagnosis, 52 with prior cataract surgery, 22 with prior laser-assisted in situ keratomileusis, and 15 with glaucoma. METHODS: Patient questionnaires were completed at baseline and after 4 weeks of treatment to assess mean change in severity of DES symptoms, ocular surface disease index (OSDI) scores, frequency of occurrence of DES symptoms, occurrence of difficulty when performing activities of daily living (ADLs), and frequency of discomfort in various environmental conditions. Mean change was measured from visit 1 to visit 2. MAIN OUTCOME MEASURES: Symptoms, OSDI scores, and measure of degree of difficulty when performing ADLs. RESULTS: Four hundred eighteen patients completed the study. Compared with baseline, this population of patients demonstrated statistically significant improvements in mean OSDI scores (P = 0.0215) and symptoms of discomfort, burning, dryness, grittiness, stinging, and light sensitivity (P < 0.05). Mean improvement in OSDI scores of patients in the 5 identified subsets of patients with comorbid conditions were significant for patients using contact lenses (P < 0.025), who had undergone prior cataract surgery (P < 0.04), and with prior laser-assisted in situ keratomileusis surgery (P < 0.05). Patients diagnosed with cataracts or glaucoma did not show significant changes in any measures in this study. Patients with DES and comorbid conditions experienced relief of symptoms and benefit to ADLs and quality of life similar to patients without comorbid conditions. CONCLUSIONS: In subsets of patients with moderate to severe DES and comorbid conditions, hydroxypropyl cellulose ophthalmic inserts improve the symptoms of DES, ability to perform ADLs, and quality of life. The reported benefits may be additive to those seen with patients' existing therapies.

Improved signs, symptoms, and quality of life associated with dry eye syndrome: hydroxypropyl cellulose ophthalmic insert patient registry.

OBJECTIVES: To evaluate the acceptability, ease of use, and efficacy of hydroxypropyl cellulose ophthalmic inserts in reducing signs and symptoms of moderate-to-severe dry eye syndrome (DES), and improving quality of life (QoL) and activities of daily living (ADL). METHODS: The multicenter, prospective, open-label, 4-week registry comprised 520 patients with bilateral DES and a history of artificial tear use, or a desire to use artificial tears within the previous week. Visit 1 encompassed a clinical evaluation and symptom and QoL questionnaires, including the Ocular Surface Disease Index. Patients were trained to use inserts, which were used once daily, thereafter, as monotherapy or with existing therapy. At visit 2, clinical evaluation and questionnaires evaluated changes in signs, symptoms, ADL, and QoL. Adverse events were monitored throughout the registry. RESULTS: There were 418 (80.4%) completers. Statistically significant improvements in discomfort, burning, dryness, grittiness, stinging, and light sensitivity, as well as clinical signs of keratitis, conjunctival staining, and tear volume were seen (P<0.05). Mean Ocular Surface Disease Index total scores improved by 21.3% (P<0.05). Blurred vision, affecting 8.7% of patients, was the most commonly reported adverse event leading to discontinuation. CONCLUSIONS: Hydroxypropyl cellulose ophthalmic inserts significantly improved signs and symptoms of moderate-to-severe DES, as well as ADL and QoL. Benefits were additive to those seen with patients' existing care.

Obesity as a disease state: a new paradigm for diagnosis and treatment.

While global prevalence of obesity continues to increase dramatically, treatment options remain less than optimal. The etiology of obesity is multifactorial, ranging from lifestyle choices such as excess food intake and insufficient physical activity, to use of medications that have weight gain as an undesirable side effect. Economic and political determinants of available foodstuffs and even social networks may also contribute to obesity. Successful management of obesity requires the understanding and acceptance of a new paradigm that identifies obesity as a disease--one defined by waist circumference--that requires treatment. Obesity meets all accepted criteria of a medical disease, including a known etiology, recognized signs and symptoms, and a range of structural and functional changes that culminate in pathologic consequences. Excess adipose tissue acts as an endocrine organ to produce excess free fatty acids, as well as tumor necrosis factor-alpha, interleukin-6, leptin, and plasminogen activator inhibitor-1. These bioactive molecules are associated with hyperinsulinemia, hyperglycemia, insulin resistance, development of diabetes, endothelial damage, and the onset and progression of atherosclerotic lesions. Options for treating obesity include lifestyle modifications (dietary changes, increased physical activity, behavior modification) and, for the morbidly obese, surgery. Lifestyle modification is rarely successful over the long term; therefore, addition of pharmacotherapy should be considered for obese individuals who have difficulty achieving and maintaining weight goals with lifestyle modifications alone. Several weight loss drugs are available for long-term use, with others in various stages of clinical development.

Overweight and obesity: the pathogenesis of cardiometabolic risk.

Obesity, particularly abdominal adiposity, is increasingly recognized as a cause of elevated cardiometabolic risk--the risk of developing type 2 diabetes mellitus (DM) and cardiovascular disease (CVD). The predominate mechanisms appear to involve the promotion of insulin resistance, driven largely by excess free fatty acids secreted by an expanded adipose tissue mass, and the development of an inflammatory milieu due to increased secretion of inflammatory cytokines and adipokines from adipose tissue. Key proinflammatory cytokines secreted by adipocytes include tumor necrosis factor-alpha, interleukin-6, leptin, resistin, and plasminogen activator inhibitor-1. All have been variously associated with hyperinsulemia, hyperglycemia, insulin resistance, diabetes, and endothelial dysfunction, as well as plaque development, progression, and rupture. Adiponectin, another important adipocyte, has protective cardiometabolic actions; however, adiponectin levels decline with increasing obesity. Understanding the role of obesity in the pathogenesis of cardiometabolic risk is crucial for the development of treatment strategies that will provide maximum benefit for patients with, or at risk for, type 2 DM and CVD.

Guiding clinical decisions on abdominal obesity and cardiometabolic risk.

Studies have shown that obesity increases cardiometabolic risk across the span of life. Obesity results in increased production of proinflammatory adipokines and decreased production of the anti-inflammatory adipokine, adiponectin, which eventually leads to atherosclerosis and type 2 diabetes mellitus. Lifestyle changes are the cornerstone for treatment of overweight and obese patients; however, pharmacotherapy and surgery are 2 additional treatment options that may be considered when lifestyle changes alone are unsuccessful. Adipose tissue, particularly central adipose tissue, is an endocrine organ, the actions of which tie together all components of cardiometabolic risk. Weight loss reduces levels of most proinflammatory adipokines, attenuates inflammation, improves endothelial function, and enhances insulin sensitivity. In view of these effects, obesity represents an obvious target for pharmacologic intervention. However, the benefits associated with the pharmacologic management of weight loss must be weighed against the potential for drug-related adverse events.

Hydroxypropyl cellulose ophthalmic inserts (lacrisert) reduce the signs and symptoms of dry eye syndrome and improve patient quality of life.

PURPOSE: A multicenter, 2-visit, open-label, 4-week study was conducted to determine the acceptability of hydroxypropyl cellulose ophthalmic inserts in adult patients with a history of dry eye syndrome (DES). METHODS: At visit 1, patients (N = 520) were evaluated, screened by slit-lamp biomicroscopy, and completed the Ocular Surface Disease Index (OSDI), a validated measure of quality of life. Patients were trained in the proper placement and use of hydroxypropyl cellulose ophthalmic inserts and were contacted by telephone on day 3 of the study. At week 4, patients were given a clinical evaluation and completed a second questionnaire. Answers determined changes in symptoms and quality of life. Adverse events were monitored throughout the study. RESULTS: Four hundred eighteen patients completed the study and reported significant improvements in discomfort, burning, dryness, grittiness, stinging, and light sensitivity (P = .05) after 4 weeks use of hydroxypropyl cellulose ophthalmic inserts. Significant improvements in clinical signs (keratitis, conjunctival staining, and tear volume) were reported. Contact lens wearers reported significant improvements similar to nonwearers, with a strong trend toward improvement in light sensitivity. Mean OSDI total scores, measuring quality of life, significantly improved by 21.3% (from 41.8 +/- 22.38 to 32.9 +/- 21.97, P < or = .0215). The most commonly reported adverse event leading to discontinuation was blurred vision, observed in 8.7% of patients (n = 45). Compliance during the study was good; 41.5% of subjects were fully compliant. Of the 58.5% of subjects who missed doses, the majority (69.4%) missed only one to five. CONCLUSIONS: Hydroxypropyl cellulose ophthalmic inserts significantly reduced symptoms and clinical signs of moderate to severe DES. They also significantly improved DES in patients wearing contact lenses. Patients experienced a statistically significant improvement in quality of life, as measured by the OSDI, of 21.3%.