Review of the safety and efficacy of exenatide once weekly for the treatment of type 2 diabetes mellitus.

OBJECTIVE: To summarize and evaluate the available literature assessing the efficacy and safety of exenatide once weekly for the treatment of type 2 diabetes mellitus. DATA SOURCES: PubMed (1966-January 2012) and International Pharmaceutical Abstracts (1969-January 2012) were searched using the term exenatide once weekly. Abstracts presented at the European Association for the Study of Diabetes Annual Meeting in 2011 and reference citations from publications were reviewed for inclusion. Eli Lilly and Company and Amylin Pharmaceuticals were contacted for additional unpublished information. STUDY SELECTION AND DATA EXTRACTION: All English-language articles and abstracts were evaluated for inclusion. All randomized controlled trials were included in the review. DATA SYNTHESIS: The efficacy and safety of exenatide once weekly has been evaluated as initial monotherapy and as add-on therapy to metformin, sulfonylureas, and thiazolidinediones in patients with uncontrolled type 2 diabetes for up to 3 years. Results from 6 randomized, comparator-controlled studies in over 3000 patients indicate that treatment with exenatide once weekly results in significant glycemic improvements and weight loss. Gastrointestinal adverse effects and injection site reactions are common, but rarely lead to drug discontinuation. CONCLUSIONS: Exenatide once weekly holds promise as a convenient, efficacious, and well-tolerated antihyperglycemic agent for the treatment of type 2 diabetes. Studies evaluating outcomes such as cardiovascular events or all-cause mortality with exenatide once weekly are lacking.

Frequency of inappropriate continuation of acid suppressive therapy after discharge in patients who began therapy in the surgical intensive care unit.

STUDY OBJECTIVE: To determine the frequency with which patients who begin to receive stress ulcer prophylaxis in the surgical intensive care unit (SICU) are discharged receiving inappropriate acid suppressive therapy (AST). DESIGN: Prospective, observational evaluation. Setting. Level 1 trauma center and academic tertiary care hospital. PATIENTS: A total of 248 consecutive adult patients admitted to the SICU during a 6-month period who began to receive AST with a proton pump inhibitor or histamine(2)-receptor antagonist. MEASUREMENTS AND MAIN RESULTS: In most patients (237 [95.6%] of 248), initiation of AST was associated with one or more risk factors for gastrointestinal bleeding. Continuation of AST during hospitalization outside the SICU occurred in 215 patients (86.7%). Sixty patients (24.2%) were discharged from the hospital receiving AST: 52 patients (21.0%) went to skilled nursing facilities or rehabilitation centers, and eight (3.2%) were discharged home. Compared with those whose AST was discontinued in the hospital, patients who continued to receive AST after hospital discharge required extended mechanical ventilation (p=0.001), had twice as many risk factors for gastrointestinal bleeding (p<0.001), were frequently discharged with anticoagulant therapy (p<0.001), exhibited longer hospital and SICU stays (p<0.001), and more frequently demonstrated Glasgow Coma Scale scores of 8 or lower and/or had head injury (p<0.001), hepatic failure (p=0.004), and major trauma (p=0.049). Evaluation of continuation of AST during hospitalization revealed that only 7.4% (16/215) of patients at SICU transfer and 5.0% (3/60) of patients at hospital discharge had a compelling risk factor to continue AST as demonstrated by a coagulopathy at discharge; no patients required mechanical ventilation at hospital discharge. CONCLUSION: Most patients inappropriately continued to receive stress ulcer prophylaxis during post-SICU hospitalization. Presence of risk factors for stress ulcer-related gastrointestinal bleeding at SICU admission appears to influence continuation of AST after discharge from the hospital. A low percentage (3.2%) of patients was discharged home receiving inappropriate AST, yet overall, few study patients demonstrated a compelling risk factor for continuation of AST.

Effects of thiazolidinediones on bone loss and fracture.

OBJECTIVE: To examine the evidence regarding the effects of thiazolidinediones on bone loss and fracture. DATA SOURCES: Published studies assessing the effects of thiazolidinediones on bone and/or fracture risk in humans were selected for review. A MEDLINE (1950-April 2007) and International Pharmaceutical Abstracts (1970-April 2007) search was performed. Search terms included thiazolidinediones, rosiglitazone, pioglitazone, troglitazone, bone, bone mineral density, fracture, and osteoporosis. STUDY SELECTION AND DATA EXTRACTION: The literature search retrieved 5 English-language studies evaluating the effects of thiazolidinediones on bone in humans. These consisted of 2 small, uncontrolled studies using troglitazone; 1 prospective, randomized controlled study and 1 retrospective cohort study using rosiglitazone; and a post hoc analysis of an observational cohort study in subjects taking various thiazolidinediones. All of the studies assessed markers of bone metabolism and/or bone mineral density (BMD). No studies were identified that addressed rate of fractures in subjects taking thiazolidinediones. DATA SYNTHESIS: The first troglitazone study demonstrated a decrease in levels of bone formation markers (10%; p < 0.05) and resorption markers (12%; p < 0.01), and authors determined that troglitazone produces a protective effect on bone through decreased bone turnover. The second troglitazone study did not demonstrate a significant change in BMD or levels of bone turnover markers. The 2 rosiglitazone studies demonstrated decreases in BMD of 1.19-1.9% with rosiglitazone use (p < 0.05). The post hoc analysis with various thiazolidinediones indicated a 2.5-fold greater decrease in BMD in women reporting thiazolidinedione use. CONCLUSIONS: Few studies have assessed the effects of thiazolidinediones on bone in humans. Studies available suggest that treatment with thiazolidinediones, primarily rosiglitazone, contributes to bone loss. The effect appears to be most prominent in postmenopausal women. More studies are needed to better understand the effects of thiazolidinediones on bone and fracture rates.