OBJECTIVE: To discuss the evolution of peroxisome proliferator-activated receptor (PPAR) agonists from single site to multiple subtype or partial agonists for the treatment of type 2 diabetes, dyslipidemia, obesity, and the metabolic syndrome. DATA SOURCES: Information was obtained from MEDLINE (1966-March 2007) using search terms peroxisome proliferator-activated receptor agonist, PPAR dual agonist, PPAR α/γ agonist, PPAR pan agonist, partial PPAR, and the specific compound names. Other sources included pharmaceutical companies, the Internet, and the American Diabetes Association 64th-66th Scientific Sessions abstract books. STUDY SELECTION AND DATA EXTRACTION: Animal data, abstracts, clinical trials, and review articles were reviewed and summarized. DATA SYNTHESIS: PPAR α, γ, and δ receptors play an important role in lipid metabolism, regulation of adipocyte proliferation and differentiation, and insulin sensitivity. The PPAR dual agonists were developed to combine the triglyceride lowering and high-density lipoprotein cholesterol elevation from the PPAR-α agonists (fibrates) with the insulin sensitivity improvement from the PPAR-γ agonists (thiazolidinediones). Although the dual agonists reduced hemoglobin A _1C (A1C) and improved the lipid profile, adverse effects led to discontinued development. Currently, PPAR-γ agonists (GW501516 in Phase I trials), partial PPAR-γ agonists (metaglidasen in Phase II and III trials), and pan agonists (α, γ, δ netoglitazone in Phase II and III trials) with improved cell and tissue selectivity are undergoing investigation to address multiple aspects of the metabolic syndrome with a single medication. By decreasing both A1C and triglycerides, metaglidasen did improve multiple aspects of the metabolic syndrome with fewer adverse effects than compared with placebo. Metaglidasen is now being compared with pioglitazone. CONCLUSIONS: Influencing the various PPARs results in improved glucose, lipid, and weight management, with effects dependent on full or partial agonist activity at single or multiple receptors. Although the dual PPAR compounds have been associated with unacceptable toxicities, new PPAR agonist medications continue to be developed and investigated to discover a safe drug with benefits in multiple disease states.

Background: A decreased capacity to self-manage medications results in nonadherence, medication errors, and drug-related problems in older adults. Previous research identified 80 electronic medication adherence products available to assist patients with self-management of medications. Unfortunately, the usability and workload of these products are unknown. Objective: This study aimed to examine the usability and workload of a sample of electronic medication adherence products. Methods: In a prospective, mixed methods study, a sample of older adults, health care professionals, and caregivers tested the usability and workload of 21 electronic medication adherence products. Each participant tested 5 products, one at a time, after which they completed the system usability scale (SUS) and NASA-task load index (NASA-TLX), instruments that measure the usability and workload involved in using a product. Higher SUS scores indicate more user-friendliness, whereas lower NASA-TLX raw scores indicate less workload when using a product. Results: Electronic medication adherence products required a mean of 12.7 steps (range 5-20) for the appropriate use and took, on average, 15.19 min to complete the setup tasks (range 1-56). Participants were able to complete all steps without assistance 55.3% of the time (103 out of the 186 tests were completed by 39 participants; range 0%-100%). The mean SUS and NASA-TLX raw scores were 52.8 (SD 28.7; range 0-100) and 50.0 (SD 25.7; range 4.2-99.2), respectively, revealing significant variability among the electronic medication adherence products. The most user-friendly products were found to be TimerCap travel size (mean 78.67, SD 15.57; P=.03) and eNNOVEA Weekly Planner with Advanced Auto Reminder (mean 78.13, SD 14.13; P=.049) as compared with MedReady 1700 automated medication dispenser (mean 28.63, SD 21.24). Similarly, MedReady (72.92, SD 18.69) was found to be significantly more work intensive when compared with TimerCap (29.35, SD 20.35; P=.03), e-pill MedGlider home medication management system (28.43, SD 20.80; P=.02), and eNNOVEA (28.65, SD 14.97; P=.03). The e-pill MedTime Station automatic pill dispenser with tipper (71.77, SD 21.98) had significantly more workload than TimerCap (P=.04), MedGlider (P=.03), and eNNOVEA (P=.04). Conclusions: This study demonstrated that variability exists in the usability and workload of different electronic medication adherence products among older adults, caregivers, and clinicians. With few studies having investigated the usability and workload of electronic medication adherence products, no benchmarks exist to compare the usability and workload of these products. However, our study highlights the need to assess the usability and workload of different products marketed to assist with medication taking and provides guidance to clinicians regarding electronic medication adherence product recommendations for their patients. Future development of electronic medication adherence products should ensure that the target populations of patients are able to use these products adequately to improve medication management.