Gina J. Ryan

National Estimates of Insulin-related Hypoglycemia and Errors Leading to Emergency Department Visits and Hospitalizations

IMPORTANCE Detailed, nationally representative data describing high-risk populations and circumstances involved in insulin-related hypoglycemia and errors (IHEs) can inform approaches to individualizing glycemic targets. OBJECTIVE To describe the US burden, rates, and characteristics of emergency department (ED) visits and emergency hospitalizations for IHEs. DESIGN, SETTING, AND PARTICIPANTS Nationally representative public health surveillance of adverse drug events among insulin-treated patients seeking ED care (National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project) and a national household survey of insulin use (the National Health Interview Survey) were used to obtain data from January 1, 2007, through December 31, 2011. MAIN OUTCOMES AND MEASURES Estimated annual numbers and estimated annual rates of ED visits and hospitalizations for IHEs among insulin-treated patients with diabetes mellitus. RESULTS Based on 8100 National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance cases, an estimated 97,648 (95% CI, 64,410-130,887) ED visits for IHEs occurred annually; almost one-third (29.3%; 95% CI, 21.8%-36.8%) resulted in hospitalization. Severe neurologic sequelae were documented in an estimated 60.6% (95% CI, 51.3%-69.9%) of ED visits for IHEs, and blood glucose levels of 50 mg/dL (to convert to millimoles per liter, multiply by 0.0555) or less were recorded in more than half of cases (53.4%). Insulin-treated patients 80 years or older were more than twice as likely to visit the ED (rate ratio, 2.5; 95% CI, 1.5-4.3) and nearly 5 times as likely to be subsequently hospitalized (rate ratio, 4.9; 95% CI, 2.6-9.1) for IHEs than those 45 to 64 years. The most commonly identified IHE precipitants were reduced food intake and administration of the wrong insulin product. CONCLUSIONS AND RELEVANCE Rates of ED visits and subsequent hospitalizations for IHEs were highest in patients 80 years or older; the risks of hypoglycemic sequelae in this age group should be considered in decisions to prescribe and intensify insulin. Meal-planning misadventures and insulin product mix-ups are important targets for hypoglycemia prevention efforts.

Chromium as adjunctive treatment for type 2 diabetes

OBJECTIVE: To review the chemistry, pharmacology, efficacy, and safety of trivalent chromium in the treatment of type 2 diabetes and hyperlipidemia. DATA SOURCES: The English literature was searched from 1966 through May 2002 using MEDLINE, International Pharmaceutical Abstracts, and EMBASE. The key words included chromium, glucose, lipids, and diabetes. Pertinent references from review articles and studies were used as additional sources. DATA SYNTHESIS: Trivalent chromium is an essential nutrient and has a key role in lipid and glucose metabolism. Supplementation with chromium does not appear to reduce glucose levels in euglycemia. It may, however, have some efficacy in reducing glucose levels in hyperglycemia. The effects of chromium on lipid levels are variable. Chromium in doses <1000 μg/d appears to be safe for short-term administration. Kidney function and dermatologic changes need to be monitored. CONCLUSIONS: Chromium appears to be a safe supplement and may have a role as adjunctive therapy for treatment of type 2 diabetes. Additional large-scale, long-term, randomized, double-blind studies examining the effect of various doses and forms of chromium are needed.

Review of pramlintide as adjunctive therapy in treatment of type 1 and type 2 diabetes

Pramlintide (Symlin®), a synthetic analog of a neurohormone amylin, was approved by the US Food and Drug Administration for use along with premeal insulin in patients with type 1. In patients with type 2 diabetes, pramlintide is approved for addition to premeal insulin in those patients who are either only on premeal insulin or those receiving the combination of insulin and metformin and/or a sulfonylurea. This article reviews the pharmacology, pharmacokinetics, dosing, clinical trials, safety, contraindications, and drug interactions of pramlintide therapy. A search for published clinical trials and therapeutic reviews in the English language was done in the following databases: Iowa Drug Information Service (1966 to July 2008), MEDLINE (1966 to July 2008), and International Pharmaceutical Abstracts (1970 to July 2008). Pramlintide and amylin were used as keywords and title words. References of key articles were also reviewed to identify additional publications. Amylin is a 37 amino acid peptide neurohormone cosecreted from the beta cells of the pancreas, along with insulin, in response to meals. Amylin lowers serum glucose by decreasing glucagon release, slowing gastric emptying and decreasing food intake. Pramlintide, a synthetic analog of amylin, reduces 2-hour postprandial blood glucose between 3.4 and 5 mmol/L, reduces A1C by 0.2% to 0.7% and has no effect on fasting glucose levels. The use of pramlintide was associated with up to a 1.6 kg weight loss. Nausea was the most commonly reported adverse event. Pramlintide is an amylin analog that was FDA approved for the treatment of type 1 and type 2 diabetes. Its use results in modest reduction of A1C and the most frequent side effects are hypoglycemia and nausea.

The Safety of Metformin in Heart Failure

Objective: To examine the evidence regarding the safety of metformin in heart failure. Data Sources: Searches in MEDLINE and International Pharmaceutical Abstracts were performed (1966–February 2007). Search terms included metformin, heart failure, lactic acidosis, clinical trials, and insulin resistance. Study Selection and Data Extraction: Published studies and case reports that evaluated the causal link between metformin and lactic acidosis in patients with heart failure were selected for review. Data Synthesis: There were no case reports of patients who had metformin-associated lactic acidosis when heart failure was the only contraindication, Two large retrospective studies showed that metformin does not increase the risk of lactic acidosis in patients with heart failure. However, these retrospective analyses did not account for many important confounding variables. A reduction in mortality rates in metformin users with New York Heart Association Class III and IV heart failure was observed in one small (N = 94) prospective trial. Conclusions: Results from 3 trials suggest that metformin may be safe to use in heart failure. Large prospective trials are needed to provide conclusive evidence regarding metformins safety. Until then, use of metformin in heart failure patients should not be recommended routinely. If it is used in patients with heart failure, they should be monitored closely for signs of lactic acidosis.

Analysis of trials evaluating combinations of acetylsalicylic acid and dipyridamole in the secondary prevention of stroke

BACKGROUND Stroke is one of the leading causes of morbidity and mortality in the United States. Patients who suffer a cerebrovascular event are at high risk of a recurrence, and secondary prevention is crucial to reducing the burden of cerebrovascular disease. Acetylsalicylic acid (ASA, aspirin) is an established method of stroke prophylaxis. OBJECTIVE This review investigates whether the addition of dipyridamole to ASA further reduces the risk of stroke recurrence. METHODS To identify clinical trials of the use of combinations of ASA and dipyridamole in the prevention of recurrent stroke in patients who have suffered a first stroke or transient ischemic attack, the English-language literature was searched from 1966 through May 2001 using the MEDLINE, International Pharmaceutical Abstracts, EMBASE, and BIOSIS databases. The search terms used were dipyridamole, aspirin, acetylsalicylic acid, ischemic stroke, and cerebrovascular disorders. CONCLUSIONS Of the 5 published studies, 3 earlier studies detected no differences in outcome when dipyridamole was added to ASA therapy for stroke prophylaxis. Two more recent trials found that the addition of dipyridamole to ASA therapy provided further reduction in the risk of secondary cerebrovascular events compared with placebo and with ASA alone. Further studies are needed to confirm long-term benefit.

Liraglutide: once-daily GLP-1 agonist for the treatment of type 2 diabetes.

What is known and Objective:  The prevalence of diabetes is increasing worldwide. Over the recent years, new discoveries have led to the development of new pharmacological agents targeting the incretin hormones gastric inhibitory peptide (GIP) and glucagon‐like peptide‐1 (GLP‐1). These agents, called incretin‐mimetics, are the newest agents added to the diabetes treatment options. The purpose of this article is to review the relevant literature on the chemistry, pharmacology, pharmacokinetics, metabolism, clinical trials, safety, drug interactions and place in therapy of liraglutide in the treatment of type 2 diabetes.Summary What is known and Objective:  The prevalence of diabetes is increasing worldwide. Over the recent years, new discoveries have led to the development of new pharmacological agents targeting the incretin hormones gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1). These agents, called incretin-mimetics, are the newest agents added to the diabetes treatment options. The purpose of this article is to review the relevant literature on the chemistry, pharmacology, pharmacokinetics, metabolism, clinical trials, safety, drug interactions and place in therapy of liraglutide in the treatment of type 2 diabetes. Methods:  An extensive search of the literature was performed with liraglutide and NN2211 as key terms. This article presents a review of the literature related to the chemistry, pharmacology, pharmacokinetics, drug interactions and safety and efficacy of liraglutide. Results and Discussion:  Liraglutide, a subcutaneously administered GLP-1 agonist, displays phamacodynamic and pharmacokinetic properties that allow for once-daily administration. The agent has been shown to be efficacious as monotherapy, as well as in combination with glimperide, metformin and/or rosiglitazone, reducing glycoslyated haemoglobin (A1C) between 0·84% and 1·5%. The primary adverse event reported with liraglutide is transient nausea. What is new and conclusion:  Liraglutide has been well studied in dual and triple combination therapies with sulfonylureas, metformin and rosiglitazone and appears safe and effective. For patients who cannot tolerate first-line agents, metformin, insulin and sulfonylureas, liraglutide is a reasonable treatment option.

Reduced-Dose Influenza Vaccine:

Objective: To evaluate the effectiveness and safety of reduced-dose trivalent inactivated influenza vaccine in adults. Data Sources: A MEDLINE search was conducted (1966–May 2006) using the key search terms inactivated, trivalent, influenza vaccine, dose, and intradermal. Data Synthesis: Four recent studies evaluated the safety and effectiveness of reduced-dose, inactivated, trivalent influenza vaccine. Reduced doses had immunogenicity similar to that of standard dose vaccination in healthy individuals less than 60 years old. Intramuscular administration caused fewer local adverse effects compared with the other routes of administration. The differences in vaccine administration and dosing used in these studies limit the comparison of their results. Conclusions: The Centers for Disease Control and Prevention does not recommend vaccinating with reduced-dose influenza vaccine. If reduced-dose vaccination is to be employed during times of vaccine shortage, it should be administered only to healthy adults under the age of 60, and the intramuscular route is preferred.

Dipeptidyl peptidase-4 inhibitor use in patients with type 2 diabetes and cardiovascular disease or risk factors

Abstract Objectives: Management of cardiovascular (CV) risk is an essential aspect of diabetes care, and acceptable CV risk is a requirement for antidiabetes medications. Dipeptidyl peptidase-4 (DPP-4) inhibitors effectively reduce glycated hemoglobin, with a low risk of hypoglycemia and weight gain. The purpose of this review is to discuss the use of DPP-4 inhibitors in patients with type 2 diabetes mellitus (T2DM) and CV disease or risk factors. Methods: A PubMed search (January 2013–June 2015) was conducted to identify prospective trials, meta-analyses, pooled analyses and cohort studies evaluating CV outcomes with DPP-4 inhibitors. Results: Meta-analyses, pooled analyses and retrospective cohort studies in patients with T2DM suggest no increased CV risk and possible CV benefit compared with some antidiabetes medications. The three published, long-term, prospective, randomized, double-blind CV outcomes trials in patients with CV disease or risk factors found no increased rate of major CV events in patients treated with alogliptin, saxagliptin or sitagliptin versus placebo as add-on to standard-of-care. However, the analysis of the components of the secondary end point of the saxagliptin study showed an increased number of hospitalizations for heart failure (HF) in treated patients versus placebo. A post hoc analysis of the alogliptin study showed no increase in HF hospitalization in treated patients with a history of HF versus placebo, but did show an increase in alogliptin-treated patients with no baseline HF history. Sitagliptin showed no increased risk for HF hospitalization versus placebo in the overall cohort. Two CV outcomes trials for linagliptin are ongoing. Conclusion: The majority of available data from CV outcomes trials suggest a neutral effect of DPP-4 inhibitors on major CV events.

Overcoming insulin “resistance”: Assisting patients in transitioning to insulin therapy

The American Diabetes Association (ADA) recommends metformin, sulfonylureas, or insulin as first-tier therapy for treating type 2 diabetes.[1][1] Insulin is recommended as the treatment of choice if a patient’s fasting blood glucose concentration exceeds 250 mg/dL or glycosylated hemoglobin

Medication reconciliation: comparing a customized medication history form to a standard medication form in a specialty clinic (CAMPII 2).

Background Medication history forms completed by patients are an essential part of the medication reconciliation process. Objective In a crossover prospective study, investigators compared the accuracy and acceptability of a “fill-in-the blank” medication history form (USUAL) to a customized form (CUSTOM) that contained a checklist of the 44 most frequently prescribed diabetes clinic medications. Methods The content of both forms was compared to a “gold-standard” medication list compiled by a clinical pharmacist who conducted a medication history and reviewed pharmacy profiles and medical chart. Subject preference and time to complete the forms were also determined. Accurate was defined as complete and correct (name, dose, and frequency) relative to the gold standard. Results A total of 77 subjects completed both forms. Complete list accuracy was poor; there was no difference in the accuracy between CUSTOM (6.5%) and USUAL (9.1%) (odds ratio [OR], 0.33; P = 0.62). Out of a total of 648 medications, subjects accurately listed 43.7% of medications on CUSTOM and 45.5% on USUAL (OR, 0.88; P = 0.41). The 44 medications on the checklist were more than twice as likely to be accurately reported using CUSTOM than with USUAL (OR, 2.1; P = 0.0002). More subjects preferred CUSTOM (65.7%) compared with USUAL (32.8%, P = 0.007). Conclusion Medication self-report is very poor, and few subjects created an accurate list on either form. Subjects were more likely to report the drugs on the checklist using CUSTOM than when they used USUAL; however, there was no difference in the overall accuracy between CUSTOM and USUAL.