Jonathan Betz Brown

To document the extent to which drug naïve patients with diabetes continued newly initiated metformin monotherapy, and who subsequently experienced primary failure or therapeutic success. Using an observational longitudinal cohort design, we identified all 3116 type 2 diabetes patients who initiated metformin monotherapy as their first-ever anti-hyperglycemic drug in 2004–2006. We defined initial nonadherence as having occurred in the first 6 months if a patient (1) received only a single metformin dispense, (2) received less than a 90 day supply, or (3) switched to a second anti-hyperglycemic agent. Among those patients who continued metformin monotherapy for at least 6 months, we determined the proportion attaining A1C < 7% by examining A1Cs recorded prior to adding a second anti-hyperglycemic agent or December 31, 2008, whichever occurred first. We identified factors associated with achieving A1C < 7% with logistic regression. Initial nonadherence occurred in 518 (16.6%) of the 3116 patients studied. Of those who continued metformin for at least 6 months, a majority (71.7% overall) achieved an A1C < 7%, even when pre-metformin A1C was high (59.6% among those with A1C > 9%). Initiating metformin within 3 months of diagnosis increased the probability of success nearly three-fold compared to initiating after 12–23 months (OR 2.85, 95% CI 2.04–3.98). Independent of duration, lower A1C at initiation increased the probability of success. Initiating metformin immediately at diagnosis and while A1C is still low substantially increases the probability of attaining glycemic success. Our findings support the current guidelines recommending metformin therapy as soon as type 2 diabetes is diagnosed. This study was limited by its observational design, the inability to assess reasons for metformin nonadherence, and the highly automated study setting.

Investigators from the Framingham Offspring Study (FOS) recently proposed a new simple point score for estimating 8-year diabetes mellitus (DM) risk. To validate prediction models and to compare DM risk estimated by the point score with observed DM incidence. Longitudinal observational cohort study. We identified 20,644 members of Kaiser Permanente Northwest (KPNW) who had no prior evidence of DM and who had all data elements necessary to estimate the models recorded between July 1, 1999, and June 30, 2000. Patients were followed up through June 30, 2007. We reestimated the FOS logistic regression models in the total KPNW sample (cumulative DM incidence, 16.5%) and in a randomly selected subsample with incidence identical to that in the FOS (5.1%). We also compared DM risk predicted by the FOS point score with actual 8-year DM incidence observed in the KPNW samples. The prediction models performed similarly in the FOS and KPNW samples, with almost identical odds ratios for independent variables and areas under the receiver operating characteristic curves for the models. The FOS point score substantially underestimated actual DM incidence in the total sample. In the subsample with DM incidence identical to that in the FOS sample, the point score was extremely accurate. The accuracy of the point score requires that the underlying incidence of the individuals to whom it is applied be similar to the population from which it was derived. Accurate adaptation requires recalculating DM incidence at each point level.

OBJECTIVE—In type 2 diabetes, therapies to maintain blood glucose control usually fail after several years. We estimated the glycemic burden that accumulates from treatment failure and describe the time course and predictors of failure. RESEARCH DESIGN AND METHODS—A prospective, population-based study using retrospective observational data. We identified all 7,208 complete courses of treatment with nondrug therapy, sulfonylurea monotherapy, metformin monotherapy, and combination oral antihyperglycemic therapy between 1994 and 2002, inclusive, among members of the Kaiser Permanente Northwest Region. We calculated mean cumulative glycemic burden, defined as HbA_1c-months >8.0 or 7.0% for each treatment. We then measured the likelihood that the next HbA_1c would exceed 8.0 and 7.0% after HbA_1c exceeded each of ten hypothetical treatment thresholds. Finally, we estimated multivariate logistic regression models to predict when HbA_1c would continue to deteriorate. RESULTS—In this well-controlled population, the average patient accumulated nearly 5 HbA_1c-years of excess glycemic burden >8.0% from diagnosis until starting insulin and about 10 HbA_1c-years of burden >7.0%. Whenever patients crossed the American Diabetes Association-recommended treatment threshold of 8.0%, their next HbA_1c result was as likely to be 8.0%. Multivariate prediction models had highly statistically significant coefficients, but predicted 1c results. CONCLUSIONS—Clinicians should change glucose-lowering treatments in type 2 diabetes much sooner or use treatments that are less likely to fail. An action point at 7.0% or lower is more likely to prevent additional deterioration than the traditional action point of 8.0%.

OBJECTIVE—To measure the extent to which modern intensified risk factor control has lessened the duration-specific prevalence of diabetic retinopathy and, therefore, has decreased the risk of blindness in Americans with type 2 diabetes.

To describe how primary care clinicians' perceptions about depression care as a clinical activity changed during the adoption of selective serotonin reuptake inhibitors (SSRIs) in their health maintenance organization (HMO). Prospective study of change in primary care clinicians' level of satisfaction from depression care activities from time 1 (mid-1993) to time 2 (early 1995). Study subjects were internal medicine and family practice physicians, physician assistants, and nurse practitioners (n = 196) in a large, not-for-profit group-model HMO. We modeled level of satisfaction from depression care activities at time 2 as a function of changes in depression-care-related attitudes and perceptions over the study period, controlling for time 1 level of satisfaction and personal and professional characteristics. Overall satisfaction showed a small, statistically significant improvement over the study period. Time 2 satisfaction was a function of improved perceptions about the feasibility of primary care treatment of depression, which in turn were related to improved perceptions about the effectiveness of drug treatment. The relevance of clinicians' perceptions about their own depression care skills declined concomitantly. The adoption of SSRIs in the HMO was associated with improvement in primary care clinicians' perceptions about their ability to successfully treat depression (especially using pharmacology) and in their overall satisfaction from depression care activities. Future research should address whether reliance on SSRIs replaces the use of other depression treatment modalities, and if so, how this reliance affects patient outcomes and satisfaction and overall healthcare costs.

NUMEROUS randomized controlled trials^1,2 demonstrate the value of oral antithrombotic therapy in preventing myocardial infarction (MI), ischemic stroke, and vascular death in patients with clinical atherosclerotic cardiovascular disease (CVD). Two types of oral antithrombotic agents are available—antiplatelet agents and anticoagulants. Aspirin is the most extensively studied and by far the most frequently used antiplatelet agent. Regular use of low-dose aspirin for the secondary prevention of atherothrombotic events in patients with established CVD is widely recommended.^3,4 In addition to aspirin, 3 other oral antiplatelet agents—clopidogrel bisulfate, ticlopidine hydrochloride, and dipyridamole—and 1 oral anticoagulant—warfarin sodium—are used in the United States. While studies^5,6 consistently report that most patients with acute MI receive orders for aspirin on hospital discharge, data on the long-term use of antithrombotic agents among outpatients with CVD are limited and inconsistent. In the Atherosclerosis Risk in Communities Study,⁷ only 53% of middle-aged subjects with a self-reported history of MI, and 37% of those with a self-reported history of stroke, took aspirin. More recently, Cook et al⁸ found that only 43% of respondents to the 1996 National Family Opinion Mail Panel survey with a self-reported history of CVD reported taking aspirin regularly. Similarly, using data from the 1996 National Ambulatory Medical Care Survey, Stafford⁹ found that only 34% of physicians' office visits for coronary heart disease (CHD) included a report of aspirin or another antithrombotic agent as a new or continuing medication. In contrast, O'Connor et al¹⁰ reported that 71% of patients clinically diagnosed as having CHD in a nonprofit, mixed-model, midwestern health maintenance organization (HMO) took aspirin regularly. These studies suggest that the use of oral antithrombotic agents among outpatients with atherosclerotic CVD may be suboptimal in many settings.