Changing trends in type 2 diabetes mellitus treatment intensification, 2002-2010.

OBJECTIVES: Glycemic control can lower the risk of diabetes-related complications, and delayed treatment intensification can impede optimal diabetes care. This study examines trends in hyperglycemia treatment intensification between 2002 and 2010. STUDY DESIGN: Retrospective secondary data analysis of a large national administrative data set of privately insured individuals across the United States. METHODS: Adults 18 years or older with diabetes, initiated on metformin monotherapy between 2002 and 2007, were studied, stratified by date of first metformin prescription (2002-2003, 2004-2005, 2006-2007). Time to treatment intensification between 2002 and 2010, defined by the addition of ≥1 agents to metformin, was estimated using Kaplan-Meier and Cox proportional hazards regression analysis. RESULTS: There were 75,069 treatment-naïve adults with diabetes first initiated on metformin between 2002 and 2007; mean age was 60 years (SD = 11.5), 49.7% were women, and 63.1% were non-Hispanic white. Diabetes therapy was intensified in 26,169 individuals (34.6%).Treatment intensification became increasingly more likely with time for the 2004-2005 cohort (hazard ratio [HR], 1.07; 95% CI, 1.04-1.10) and for the 2006-2007 cohort (HR, 1.11; 95% CI, 1.07-1.14) compared with the 2002-2003 cohort (P < .001), after adjustment for significant confounders including sex, income level, education level, and comorbidity burden. Sulfonylureas were the most commonly used agents, though their use declined over time; thiazolidinedione use decreased; and incretin use increased (all P < .001). CONCLUSIONS: There was a significant increase in diabetes treatment intensification between 2002 and 2010. Choice of secondline agents changed as well, with decreasing prevalence of thiazolidinedione and sulfonylurea use and rising prevalence of incretin use.

Second-line agents for glycemic control for type 2 diabetes: are newer agents better?

OBJECTIVE: While metformin is generally accepted as the first-line agent in treatment of type 2 diabetes, there are insufficient evidence and extensive debate about the best second-line agent. We aimed to assess the benefits and harms of four commonly used antihyperglycemia treatment regimens considering clinical effectiveness, quality of life, and cost. RESEARCH DESIGN AND METHODS: We developed and validated a new population-based glycemic control Markov model that simulates natural variation in HbA1c progression. The model was calibrated using a U.S. data set of privately insured individuals diagnosed with type 2 diabetes. We compared treatment intensification of metformin monotherapy with sulfonylurea, dipeptidyl peptidase-4 inhibitor, glucagon-like peptide-1 receptor agonist, or insulin. Outcome measures included life-years (LYs), quality-adjusted life-years (QALYs), mean time to insulin dependence, and expected medication cost per QALY from diagnosis to first diabetes complication (ischemic heart disease, myocardial infarction, congestive heart failure, stroke, blindness, renal failure, amputation) or death. RESULTS: According to our model, all regimens resulted in similar LYs and QALYs regardless of glycemic control goal, but the regimen with sulfonylurea incurred significantly lower cost per QALY and resulted in the longest time to insulin dependence. An HbA1c goal of 7% (53 mmol/mol) produced higher QALYs compared with a goal of 8% (64 mmol/mol) for all regimens. CONCLUSIONS: Use of sulfonylurea as second-line therapy for type 2 diabetes generated glycemic control and QALYs comparable with those associated with other agents but at lower cost. A model that incorporates HbA1c and diabetes complications can serve as a useful clinical decision tool for selection of treatment options.

Optimizing statin treatment decisions for diabetes patients in the presence of uncertain future adherence.

BACKGROUND: Statins are an important part of the treatment plan for patients with type 2 diabetes. However, patients who are prescribed statins often take less than the prescribed amount or stop taking the drug altogether. This suboptimal adherence may decrease the benefit of statin initiation. OBJECTIVE: To estimate the influence of adherence on the optimal timing of statin initiation for patients with type 2 diabetes. METHOD: The authors use a Markov decision process (MDP) model to optimize the treatment decision for patients with type 2 diabetes. Their model incorporates a Markov model linking adherence to treatment effectiveness and long-term health outcomes. They determine the optimal time of statin initiation that minimizes expected costs and maximizes expected quality-adjusted life years (QALYs). RESULTS: In the long run, approximately 25% of patients remain highly adherent to statins. Based on the MDP model, generic statins lower costs in men and result in a small increase in costs in women relative to no treatment. Patients are able to noticeably increase their expected QALYs by 0.5 to 2 years depending on the level of adherence. CONCLUSIONS: Adherence-improving interventions can increase expected QALYs by as much as 1.5 years. Given suboptimal adherence to statins, it is optimal to delay the start time for statins; however, changing the start time alone does not lead to significant changes in costs or QALYs.

Development and inter-rater reliability of the Liverpool adverse drug reaction causality assessment tool.

AIM: To develop and test a new adverse drug reaction (ADR) causality assessment tool (CAT). METHODS: A comparison between seven assessors of a new CAT, formulated by an expert focus group, compared with the Naranjo CAT in 80 cases from a prospective observational study and 37 published ADR case reports (819 causality assessments in total). MAIN OUTCOME MEASURES: Utilisation of causality categories, measure of disagreements, inter-rater reliability (IRR). RESULTS: The Liverpool ADR CAT, using 40 cases from an observational study, showed causality categories of 1 unlikely, 62 possible, 92 probable and 125 definite (1, 62, 92, 125) and 'moderate' IRR (kappa 0.48), compared to Naranjo (0, 100, 172, 8) with 'moderate' IRR (kappa 0.45). In a further 40 cases, the Liverpool tool (0, 66, 81, 133) showed 'good' IRR (kappa 0.6) while Naranjo (1, 90, 185, 4) remained 'moderate'. CONCLUSION: The Liverpool tool assigns the full range of causality categories and shows good IRR. Further assessment by different investigators in different settings is needed to fully assess the utility of this tool.

Comparative effectiveness of guidelines for the management of hyperlipidemia and hypertension for type 2 diabetes patients.

BACKGROUND: Several guidelines to reduce cardiovascular risk in diabetes patients exist in North America, Europe, and Australia. Their ability to achieve this goal efficiently is unclear. METHODS AND FINDINGS: Decision analysis was used to compare the efficiency and effectiveness of international contemporary guidelines for the management of hypertension and hyperlipidemia for patients aged 40-80 with type 2 diabetes. Measures of comparative effectiveness included the expected probability of a coronary or stroke event, incremental medication costs per event, and number-needed-to-treat (NNT) to prevent an event. All guidelines are equally effective, but they differ significantly in their medication costs. The range of NNT to prevent an event was small across guidelines (6.5-7.6 for males and 6.5-7.5 for females); a larger range of differences were observed for expected cost per event avoided (ranges, $117,269-$157,186 for males and $115,999-$163,775 for females). Australian and U.S. guidelines result in the highest and lowest expected costs, respectively. CONCLUSIONS: International guidelines based on the same evidence and seeking the same goal are similar in their effectiveness; however, there are large differences in expected medication costs.

Incremental diagnostic yield of pediatric cardiac assessment after fetal echocardiography in the offspring of women with congenital heart disease: a prospective study.

OBJECTIVE: We sought to determine the incremental diagnostic utility of pediatric cardiac assessment in the offspring of women with congenital heart disease who have had previous fetal echocardiography. PATIENTS AND METHODS: We prospectively followed pregnant women with congenital heart disease who were receiving care at 2 obstetric and cardiac centers and identified 276 infants who underwent both fetal echocardiography and pediatric cardiac assessment. All of the infants with abnormal fetal echocardiography findings or abnormal pediatric cardiac assessments underwent subsequent confirmatory pediatric echocardiography. RESULTS: In this cohort, congenital heart disease was detected in 22 (8%) of 276 offspring born to women with congenital heart disease. There was concordance between the results of fetal echocardiography and pediatric cardiac assessment in 235 (85%) of 276 offspring (231, both normal; 4, both abnormal) and discordance between the results of fetal echocardiography and pediatric cardiac assessment in 41 (15%) of 276 infants. In the 41 subjects with discordant results, there were normal fetal echocardiography findings but abnormal pediatric cardiac assessments in 35 of 41 (pediatric echocardiography revealed congenital heart disease in 18 of 35 and normal anatomy in 17 of 35) and abnormal fetal echocardiography findings but normal pediatric cardiac assessments in 6 of 41 (pediatric echocardiography findings normal in all 6 of the infants). Fetal echocardiography detected all of the major forms of congenital heart disease. Lesions missed by fetal echocardiography but detected on pediatric cardiac assessment included shunt lesions and minor valvular abnormalities. CONCLUSIONS: Although fetal echocardiography can reliably exclude major forms of congenital heart disease, minor congenital heart disease lesions can be missed on fetal echocardiography; however, these can be diagnosed with careful pediatric cardiac assessment. Postnatal pediatric cardiac assessment has incremental diagnostic utility for the detection of congenital heart disease in the offspring of women with congenital heart disease and previous fetal echocardiography.

Energy and predation costs of firefly courtship signals.

Animal courtship signals include many highly conspicuous traits and behaviors, and it is generally assumed that such signals must balance the benefits of attracting mates against some fitness costs. However, few studies have assessed the multiple costs potentially incurred by any one courtship signal, so we have limited understanding of the relative importance of different costs. This study provides the first comprehensive assessment of signal costs for Photinus fireflies (Coleoptera: Lampyridae), using controlled experiments to measure both the energy and predation costs associated with their bioluminescent courtship signals. We measured energy required to generate bioluminescent flashes, using differential open-flow respirometry, and found that flash signaling results in only a nominal increase in energy expenditure above resting levels. These results suggest that the energy required to generate bioluminescent flashes represents a minor component of the total cost of firefly courtship. However, controlled field experiments revealed that visually oriented predators imposed major costs on firefly courtship signals, with higher signaling rates significantly increasing the likelihood of predation. Together with previous results demonstrating that female fireflies prefer more conspicuous courtship signals, these results support the importance of multiple-receiver communication networks in driving signal evolution.