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Objectives: Guidance to industry from the FDA requires studies to evaluate the cardiovascular safety of novel type 2 diabetes (T2D) medications. Although the objectives of such cardiovascular outcomes trials (CVOTs) are similar, differences in features such as enrollment criteria present a challenge when trying to assess the applicability of these studies to real-world T2D populations. This study evaluated the proportions of US adults with T2D who met the eligibility criteria for each of the 4 sodium-glucose cotransporter-2 (SGLT2) inhibitor CVOTs., Study Design: A cross-sectional retrospective study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) and published patient eligibility criteria for completed or ongoing SGLT2 inhibitor CVOTs., Methods: Data on T2D diagnosis and other relevant clinical and demographic characteristics were extracted from the NHANES (2009-2010 and 2011-2012). Weighted analysis of these data was used to estimate the percentage of US adults with T2D who met the eligibility criteria for the CANVAS program (CANagliflozin cardioVascular Assessment Study) (canagliflozin; NCT01032629, NCT01989754), and the DECLARE-TIMI 58 (dapagliflozin; NCT01730534), EMPA-REG OUTCOME (empagliflozin; NCT01131676), and VERTIS-CV (ertugliflozin; NCT01986881) trials., Results: The weighted analysis identified a population of 23,941,512 US adults from data on key inclusion criteria and information indicating a diagnosis of T2D. Of these, 4.1% met the criteria for EMPA-REG OUTCOME, 4.8% for VERTIS-CV, 8.8% for the CANVAS program, and 39.8% for the DECLARE-TIMI 58 trial., Conclusions: There were considerable differences in the proportions of US adults with T2D who met the eligibility criteria for these studies.The DECLARE-TIMI 58 trial criteria were the most generalizable to the US T2D population.

Objectives: The efficacy of dapagliflozin as add-on therapy to metformin has been assessed in randomized trials. However, its effectiveness has not been assessed in a US real-world setting., Methods: Electronic medical record (EMR) data were used to compare clinical outcomes among patients with type 2 diabetes (T2D) treated with dapagliflozin and metformin with or without other oral antidiabetic drugs (D + M ± OAD), versus metformin with at least 1 other OAD (M + OAD). Adult patients with T2D on these regimens from January 01, 2014, to February 28, 2015, were identified in a US EMR database, with the date of first prescription for dapagliflozin (D + M ± OAD) or other OAD (M + OAD) as the index date. Patients were observed for 12 months before the index date (baseline) and 12 months afterward (ie, follow-up). Patients in the M + OAD group were propensity score matched 1:1 to those in the D + M ± OAD group. Outcomes included change in glycated hemoglobin (A1C) level, weight, and systolic and diastolic blood pressures (SBP/DBP) from baseline to follow-up., Results: A total of 1093 patients receiving M + OAD were matched to 1093 patients receiving D + M ± OAD. Compared with those given M + OAD, patients given D + M ± OAD had a greater reduction in A1C level (mean, -1.0% vs -0.7%; P <.01), greater weight loss (-1.8 kg vs -0.7 kg, P <.01), and greater change in SBP (-3.6 mm Hg vs -0.1 mm Hg, P <.01) and DBP (-2.0 mm Hg vs -0.6 mm Hg, P <.01) from baseline to follow-up., Conclusions: In current US clinical practice, patients receiving D + M ± OAD had greater reductions in important clinical outcomes of T2D-A1C level, weight loss, and blood pressure-versus patients receiving M + OAD. This study supports the use of dapagliflozin as add-on therapy to metformin with or without other OADs for patients with T2D.

Objectives: Cardiovascular outcomes trials (CVOTs) for evaluating the safety of novel antidiabetic agents are required by the FDA. CVOTs vary in their design and inclusion criteria, making it difficult to evaluate their applicability to the general population. This study examined the proportion of adults eligible for 7 ongoing or completed glucagon-like peptide-1 receptor agonist (GLP-1 RA) CVOTs., Study Design: This cross-sectional, retrospective, cohort study compared data from the National Health and Nutrition Examination Survey (NHANES) with published eligibility criteria from GLP-1 RA CVOTs., Methods: Patient information on T2D status and other relevant characteristics were extracted from the 2009 to 2010 and the 2011 to 2012 NHANES. Weighted analyses of these data were used to calculate the numbers of adults with T2D in the US population who would have met eligibility criteria for enrollment in the following published or ongoing CVOTs: ELIXA (lixisenatide; NCT01147250), EXSCEL (Exenatide Study of Cardiovascular Event Lowering) (exenatide once weekly; NCT01144338), FREEDOM-CVO (exenatide via ITCA 650 miniature osmotic pump; NCT01455896), HARMONY Outcomes (albiglutide; NCT02465515), LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results) (liraglutide; NCT01179048), REWIND (Researching Cardiovascular Events With a Weekly INcretin in Diabetes) (dulaglutide; NCT01394952), and SUSTAIN-6 (semaglutide; NCT01720446)., Results: The proportion of adults with T2D eligible for enrollment varied substantially among CVOTs (6.4%-47.2%); EXSCEL, which had a pragmatic study design, had the most generalizable inclusion criteria. More than 60% of patients with T2D would have qualified for enrollment into at least 1 GLP-1 RA CVOT., Conclusions: Most adults with T2D in the United States would have qualified for enrollment into at least 1 of the GLP-1 RA CVOTs evaluated. EXSCEL had the most generalizable eligibility criteria of these trials and ELIXA the least.

Objectives: The objective was to compare the use of low-dose liraglutide (LD-L) (Victoza) to the other glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients without a type 2 diabetes (T2D) diagnosis in the post approval period for high-dose liraglutide (HD-L) (Saxenda), which is not indicated for T2D., Study Design: This was a retrospective, repeated cross-sectional, cohort study., Methods: Adult patients with T2D with more than 1 prescription for a GLP-1 RA in the Optum Humedica database between December 2014 and March 2016 were included. The proportions of patients without a T2D diagnosis who were prescribed L-DL versus the other GLP-1 RAs and within each cohort were computed. Logistic regression models estimated the predictive value of either treatment in those without a T2D diagnosis, controlling for multiple factors. To supplement these findings, administrative claims data were extracted from the Truven Health MarketScan database., Results: Analyses identified 11,245 patients prescribed LD-L and 4134 patients prescribed other GLP-1 RAs. For the entire study period, Humedica data revealed that patients without T2D accounted for 2.7% of the GLP-1 RA cohort and 17.5% of the LD-L cohort. Multivariable logistic regression analyses identified that patients receiving LD-L were more than 6 times likely to have no indication of T2D relative to patients taking other GLP-1 RAs. Claims data from MarketScan corroborated the Humedica results., Conclusions: In patients without a T2D diagnosis, LD-L use was significantly greater than that with other GLP-1 RAs within 6 months after approval of HD-L; differences persisted until the end of the study. Increased payer scrutiny of appropriate LD-L use is warranted.

Objectives: To determine whether early symptom improvement with adjunctive aripiprazole in major depressive disorder (MDD) predicts overall symptom remission., Study Design: Post hoc pooled analysis of 3 randomized, double-blind studies evaluating efficacy, safety, and tolerability of adjunctive aripiprazole or placebo with standard antidepressant therapy (ADT) in inadequate responders to a prospective 8-week ADT and at least 1 historical ADT., Methods: A multivariate logistic regression model was developed to determine factors predicting remission most strongly at the end point. Remission was defined as a Montgomery-Asberg Depression Rating Scale (MADRS) total score of 10 or less at end point., Results: Early improvement in depression symptoms was the most significant predictor of remission. In adjunctive aripiprazole and placebo groups, improvement of 20% or more in MADRS total score (week 2) was a significant predictor of remission. At week 2, high sensitivity and high negative predictive values (NPVs) were reported for remission in both treatment arms. In the adjunctive aripiprazole arm, early improvement predicted later MADRS remission with high sensitivity (88.0%) and a high NPV (91.5%). Positive predictive value was moderate in both the adjunctive aripiprazole (45.4%) and placebo (37.5%) arms; specificity was 55.0% with adjunctive aripiprazole and 71.5% with placebo., Conclusions: Week 2 was a clinically meaningful time point to identify early improvers, and lack of improvement early in treatment was a highly significant predictor of lack of later remission. Early assessment of changes in symptoms could prove useful in clinical practice and more appropriately target healthcare costs.