BackgroundDiabetes is an important global disease, associated with significant morbidity and an increased risk of death due to chronic end-organ complications. The thiazolidinediones, used mainly as third-line agents in type 2 diabetes mellitus (T2DM), have been associated with some safety concerns, such as an increased risk of bladder cancer, an increased risk of bone fracture and heterogeneous effects on cardiovascular events.ObjectiveThis study aimed to evaluate safety data on pioglitazone for several outcomes and examine them in context with each other as well as with insulin, another third-line treatment for T2DM.MethodsThis retrospective cohort study extracted data from May 1, 2000 until June 30, 2010, from the i3 InVision Data Mart™ database. To adjust for the testing of multiple hypotheses, the Holm method was applied to endpoints representing potential harm from pioglitazone treatment, separately from those representing potential benefit from pioglitazone. The study population included patients with T2DM ≥ 45 years old who were new users of either pioglitazone or insulin. Key outcomes were incident cases of a composite of myocardial infarction (MI) or stroke requiring hospitalization; bone fracture requiring hospitalization; bladder cancer; and a composite of nine other selected cancers. Kaplan–Meier curves were generated and hazard ratios (HRs) for pioglitazone versus insulin were estimated from Cox proportional hazards models adjusted with inverse probability of treatment weights derived from propensity scores.ResultsA total of 56,536 patients (pioglitazone group 38,588; insulin group 17,948) qualified for the study. The mean follow-up was 2.2 years for pioglitazone and 1.9 years for insulin patients. Weighted survival analysis of the composite of MI and stroke, as well as the composite of nine cancers, yielded significant differences in favour of pioglitazone. For the composite of MI and stroke, the HR for pioglitazone versus insulin was 0.44 (95 % confidence interval [CI] 0.39–0.50, p < 0.0001). Modelling of the composite of nine selected cancers produced an HR of 0.78 (95 % CI 0.71–0.85, p < 0.0001). A non-statistically significant difference in favour of pioglitazone was observed in the incidence rate of bone fracture requiring hospitalization (HR 0.86, 95 % CI 0.74–1.01, p = 0.058). For bladder cancer, the overall incidence rates were relatively low and showed no significant difference between the two groups; the HR for pioglitazone versus insulin was 0.92 (95 % CI 0.63–1.33, p = 0.64).ConclusionCompared with insulin, pioglitazone was associated with a significant reduction in the risk of MI and stroke requiring hospitalization, and a significant reduction in the risk of other selected cancers. While pioglitazone treatment may be linked with a lower risk of bladder cancer and bone fracture relative to insulin, these differences were not statistically significant.

Different OAD classes were associated with different levels of risk for hypoglycemic events. Hypoglycemia was associated with a higher risk of antidiabetic treatment discontinuation and significantly increased health care costs.

Rationale: Excessive daytime sleepiness in patients with obstructive sleep apnea is associated with substantial burden of illness. Objectives: To assess treatment effects of solriamfetol, a dopamine/norepinephrine reuptake inhibitor, on daily functioning, health-related quality of life, and work productivity in participants with obstructive sleep apnea and excessive daytime sleepiness as additional outcomes in a 12-week phase 3 trial ( www.clinicaltrials.gov identifier NCT02348606). Methods: Participants ( N = 476) were randomized to solriamfetol 37.5, 75, 150, or 300 mg or to placebo. Outcome measures included the Functional Outcomes of Sleep Questionnaire short version, Work Productivity and Activity Impairment Questionnaire: Specific Health Problem, and 36-item Short Form Health Survey version 2. A mixed-effects model with repeated measures was used for comparisons with placebo. Results: Demographics, baseline disease characteristics, daily functioning, health-related quality of life, and work productivity were similar across groups. At Week 12, increased functioning and decreased impairment were observed with solriamfetol 150 and 300 mg (mean difference from placebo [95% confidence interval]) on the basis of Functional Outcomes of Sleep Questionnaire total score (1.22 [0.57 to 1.88] and 1.47 [0.80 to 2.13], respectively), overall work impairment (−11.67 [−19.66 to −3.69] and −11.75 [−19.93 to −3.57], respectively), activity impairment (−10.42 [−16.37 to −4.47] and −10.51 [−16.59 to −4.43], respectively), physical component summary (2.07 [0.42 to 3.72] and 1.91 [0.22 to 3.59], respectively), and mental component summary (150 mg only, 2.05 [0.14 to 3.96]). Common adverse events were headache, nausea, decreased appetite, and anxiety. Conclusions: Solriamfetol improved measures of functioning, quality of life, and work productivity in participants with obstructive sleep apnea and excessive daytime sleepiness. Safety was consistent with previous studies. Clinical trial registered with www.clinicaltrials.gov (NCT02348606).

This study explored trends over time in diabetes prevalence, glycemic control, and antidiabetic therapy choices among adults (18-64 years) and older adults (65 years). Factors that predict diabetes outcomes were explored. The study was cross-sectional, with data from the 1999 to 2004 National Health and Nutrition Examination Survey. The study group consisted of 1211 persons with self-reported diabetes. Other information obtained from the study included self-reported medication for diabetes, hypertension, stroke, heart failure, and health status. The survey also provided examination or laboratory tests of obesity, nephropathy, and glycosylated hemoglobin level. Descriptive and logistic regression analyses were used in the study. The study showed that the proportion of diabetics with good glycemic control increased during the period from 1999 to 2004. However, nearly half of the adults and one third of older adults with diabetes did not reach glycemic control in [2003][2004]. Overall, 59% of adults and 46% of older adults were obese. There was a high prevalence of hypertension, heart failure, stroke, and nephropathy among patients with diabetes, especially in older adults. The results indicate a high percentage of poor glycemic control among persons with diabetes. There were also a substantial number of comorbid conditions associated with diabetes. J Clin Hypertens (Greenwich). 2010;12:826-832.