IMPORTANCE Understanding cardiovascular outcomes of initiating second-line antidiabetic medications (ADMs) may help inform treatment decisions after metformin alone is not sufficient or not tolerated. To date, no studies have compared the cardiovascular effects of all major second-line ADMs during this early decision point in the pharmacologic management of type 2 diabetes. OBJECTIVE To examine the association of second-line ADM classes with major adverse cardiovascular events. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study among 132 737 insured adults with type 2 diabetes who started therapy with a second-line ADM after taking either metformin alone or no prior ADM. This study used 2011-2015 US nationwide administrative claims data. Data analysis was performed from January 2017 to October 2018. EXPOSURES Dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter 2 (SGLT-2) inhibitors, thiazolidinediones (TZDs), basal insulin, and sulfonylureas or meglitinides (both referred to as sulfonylureas hereafter). The DPP-4 inhibitors served as the comparison group in all analyses. MAIN OUTCOMES AND MEASURES The primary outcome was time to first cardiovascular event after starting the second-line ADM. This composite outcome was based on hospitalization for the following cardiovascular conditions: congestive heart failure, stroke, ischemic heart disease, or peripheral artery disease. RESULTS Among 132 737 insured adult patients with type 2 diabetes (men, 55%; aged 45-64 years, 58%; white, 63%), there were 3480 incident cardiovascular events during 169 384 person-years of follow-up. Patients were censored after the first cardiovascular event, discontinuation of insurance coverage, transition from International Classification of Diseases, Ninth Revision (ICD-9) to end of ICD-9 coding, or 2 years of follow-up. After adjusting for patient, prescriber, and health plan characteristics, the risk of composite cardiovascular events after starting GLP-1 receptor agonists was lower than DPP-4 inhibitors (hazard ratio [HR], 0.78; 95% CI, 0.63-0.96), but this finding was not significant in all sensitivity analyses. Cardiovascular event rates after starting treatment with SGLT-2 inhibitors (HR, 0.81; 95% CI, 0.57-1.53) and TZDs (HR, 0.92; 95% CI, 0.76-1.11) were not statistically different from DPP-4 inhibitors. The comparative risk of cardiovascular events was higher after starting treatment with sulfonylureas (HR, 1.36; 95% CI, 1.23-1.49) or basal insulin (HR, 2.03; 95% CI, 1.81-2.27) than DPP-4 inhibitors.
Many people with diabetes do not achieve individualized treatment targets. Therapeutic inertia, the underuse of effective therapies in preventing serious clinical end points, is a frequent, important contributor to this failure. Clinicians, patients, health systems, payors, and producers of medications, devices, and other products for those with diabetes all play a role in the development of therapeutic inertia and can all help to reduce it.
There are currently no published data regarding safety and efficacy of SGLT2 inhibitor use in the hospital. Outpatient data suggests that SGLT2 inhibitors have low hypoglycemic risk. They also decrease systolic blood pressure and can prevent cardiovascular death. The EMPA-REG study also showed a decrease in admissions for acute decompensated heart failure. There have been increasing cases of diabetic ketoacidosis, and specifically the euglycemic manifestation, associated with SGLT2 inhibitors use. We present two cases of inpatient SGLT2 inhibitor use, one of continuation of outpatient therapy and one of new initiation of therapy. We then discuss potential risks and methods to mitigate these as well as benefits of these medications in the inpatient setting. We cautiously suggest the use of SGLT2 inhibitors in the hospital. However, these must be used judiciously and the practitioner must be aware of euglycemic diabetic ketoacidosis and its risk factors in this population.
Background Diabetes is present in 10.5% of the US population and accounts for 14.3% of all office-based physician visits made by adults. Despite this established office-based approach, the disease and its adverse outcomes including glycemic control and clinical events tend to worsen over time. Available home technology now provides accurate, reliable data that can be transmitted directly to the electronic medical record. Objective This study aims to evaluate the impact of a virtual, home-based diabetes management program on clinical measures of diabetes control compared to usual care. Methods We evaluated glycemic control and other diabetes-related measures after 1 year in 763 patients with type 2 diabetes enrolled into a home-based digital medicine diabetes program and compared them to 794 patients matched for age, sex, race, BMI, hemoglobin A1c (HbA1c), creatinine, estimated glomerular filtration rate, and insulin use in a usual care group after 1 year. Digital medicine patients completed questionnaires online, received medication management and lifestyle recommendations from a clinical pharmacist or advanced practice provider and a health coach, and were asked to submit blood glucose readings using a commercially available Bluetooth-enabled glucose meter that transmitted data directly to the electronic medical record. Results After 1 year, usual care patients demonstrated no significant changes in HbA1c (mean 7.3, SE 1.7 to mean 7.3, SE 1.6; P=.41) or changes in the proportion of patients with HbA1c≥9.0 (n=117, 15% to n=113, 14%; P=.51). Digital medicine patients demonstrated improvements in HbA1c (mean 7.3, SE 1.5 to mean 6.9, SE 1.2; P<.001) and significant changes in the proportion of patients with HbA1c≥9.0 (n=107, 14% to n=49, 6%; P<.001), diabetes distress (n=198, 26% to n=122, 16%; P<.001), and hypoglycemic episodes (n=313, 41.1% to n=91, 11.9%; P<.001). Conclusions A digital diabetes program is associated with significant improvement in glycemic control and other diabetes measures. The use of a virtual health intervention using connected devices was widely accepted across a broad range of ethnic diversity, ages, and levels of health literacy.
Objective: Central diabetes insipidus can occur in the setting of primary or metastatic tumors that disrupt the hypothalamic-pituitary axis. Usual treatment consists of water intake to replace ongoing fluid losses and desmopressin administration aimed at decreasing the urine output to enable maintenance of eunatremia without polyuria. Marked derangement in plasma sodium concentration can occur when high-volume intravenous fluid administration is required during chemotherapy to prevent nephrotoxicity, particularly if obligate fluid intake exceeds the total daily fluid intake necessary to maintain eunatremia. Methods: We developed a protocol for a rapidly titratable low-dose continuous intravenous arginine vasopressin infusion to maintain eunatremia in patients with central diabetes insipidus during periods of obligate fluid intake. Results: We successfully maintained eunatremia in 2 patients with central nervous system lymphoma who underwent several cycles of obligate intravenous fluid administration with 5% dextrose in 0.45% sodium chloride for chemotherapy. Conclusion: Obligate fluid administration can result in dangerous and severe fluctuations in plasma sodium concentration in patients with central diabetes insipidus receiving conventional desmopressin therapy. The use of a rapidly titratable low-dose continuous vasopressin infusion successfully maintained eunatremia in this setting. This protocol can be replicated to prevent the wide and potentially dangerous fluctuations in plasma sodium concentration that can occur in patients with central diabetes insipidus who require high-volume intravenous fluid administration. This protocol has not been assessed among patients with impaired renal function and, thus, may not be generalizable to this population. (AACE Clinical Case Rep. 2018;4:e487-e492)
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