Objective To evaluate the relation between adherence to drug therapy, including placebo, and mortality. Design Meta-analysis of observational studies. Data sources Electronic databases, contact with investigators, and textbooks and reviews on adherence. Review methods Predefined criteria were used to select studies reporting mortality among participants with good and poor adherence to drug therapy. Data were extracted for disease, drug therapy groups, methods for measurement of adherence rate, definition for good adherence, and mortality. Results Data were available from 21 studies (46 847 participants), including eight studies with placebo arms (19 633 participants). Compared with poor adherence, good adherence was associated with lower mortality (odds ratio 0.56, 95% confidence interval 0.50 to 0.63). Good adherence to placebo was associated with lower mortality (0.56, 0.43 to 0.74), as was good adherence to beneficial drug therapy (0.55, 0.49 to 0.62). Good adherence to harmful drug therapy was associated with increased mortality (2.90, 1.04 to 8.11). Conclusion Good adherence to drug therapy is associated with positive health outcomes. Moreover, the observed association between good adherence to placebo and mortality supports the existence of the "healthy adherer" effect, whereby adherence to drug therapy may be a surrogate marker for overall healthy behaviour.

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OBJECTIVE -Numerous studies have identified an increased risk of cancer in type 2 diabetes. We explored the association between antidiabetic therapies and cancer-related mortality in patients with type 2 diabetes, postulating that agents that increase insulin levels might promote cancer.RESEARCH DESIGN AND METHODS -This was a population-based cohort study using administrative databases from Saskatchewan Health. Cancer-related mortality was compared among inception cohorts of metformin users and sulfonylurea monotherapy users. Multivariate Cox regression was used to estimate the hazard ratio (HR) of cancer-related mortality, after adjusting for age, sex, insulin use, and chronic disease score. All statistical tests were two-sided.RESULTS -We identified 10,309 new users of metformin or sulfonylureas with an average follow-up of 5.4 Ϯ 1.9 years (means Ϯ SD). The mean age for the cohort was 63.4 Ϯ 13.3 years, and 55% were men. Cancer mortality over follow-up was 4.9% (162 of 3,340) for sulfonylurea monotherapy users, 3.5% (245 of 6,969) for metformin users, and 5.8% (84 of 1,443) for subjects who used insulin. After multivariate adjustment, the sulfonylurea cohort had greater cancer-related mortality compared with the metformin cohort (adjusted HR 1.3 [95% CI 1.1-1.6]; P ϭ 0.012). Insulin use was associated with an adjusted HR of cancer-related mortality of 1.9 (95% CI 1.5-2.4; P Ͻ 0.0001).CONCLUSIONS -Patients with type 2 diabetes exposed to sulfonylureas and exogenous insulin had a significantly increased risk of cancer-related mortality compared with patients exposed to metformin. It is uncertain whether this increased risk is related to a deleterious effect of sulfonylurea and insulin or a protective effect of metformin or due to some unmeasured effect related to both choice of therapy and cancer risk. Diabetes Care 29:254 -258, 2006A number of epidemiologic studies have identified an increased risk of development of cancer in people with type 2 diabetes (1-14). The association appears to be mediated through the metabolic syndrome (also known as the insulin resistance syndrome). The metabolic syndrome is present in almost onehalf of all older individuals and is a condition associated with hyperinsulinemia, insulin resistance, and a predilection to type 2 diabetes (15).There is also evidence that impaired glucose tolerance and insulin resistance may lead to an increased risk of cancer (16). Insulin is a growth-promoting hormone with mitogenic effects (17,18). Several animal studies, complemented by case studies in humans, have demonstrated the critical role of insulin-like growth factor in all stages of mammalian growth (19). Thus, it has been suggested that hyperinsulinemia combined with insulin resistance might promote carcinogenesis (16,20 -23).Despite the recognition of the potential link between type 2 diabetes and cancer, very little is known about the role that antidiabetic therapies might have on this relationship. This role is particularly noteworthy because there are treatments for diabetes that increas...

The cost of drug-related morbidity and mortality in the ambulatory setting in the United States is considerable and should be considered in health policy decisions with regard to pharmaceutical benefits. Policies and services should be developed to reduce and prevent drug-related morbidity and mortality.

OBJECTIVEType 2 diabetes is associated with an increased risk of several types of cancer and with reduced survival after cancer diagnosis. We examined the hypotheses that survival after a diagnosis of solid-tumor cancer is reduced in those with diabetes when compared with those without diabetes, and that treatment with metformin influences survival after cancer diagnosis.RESEARCH DESIGN AND METHODSData were obtained from >350 U.K. primary care practices in a retrospective cohort study. All individuals with or without diabetes who developed a first tumor after January 1990 were identified and records were followed to December 2009. Diabetes was further stratified by treatment regimen. Cox proportional hazards models were used to compare all-cause mortality from all cancers and from specific cancers.RESULTSOf 112,408 eligible individuals, 8,392 (7.5%) had type 2 diabetes. Cancer mortality was increased in those with diabetes, compared with those without (hazard ratio 1.09 [95% CI 1.06–1.13]). Mortality was increased in those with breast (1.32 [1.17–1.49]) and prostate cancer (1.19 [1.08–1.31]) but decreased in lung cancer (0.84 [0.77–0.92]). When analyzed by diabetes therapy, mortality was increased relative to nondiabetes in those on monotherapy with sulfonylureas (1.13 [1.05–1.21]) or insulin (1.13 [1.01–1.27]) but reduced in those on metformin monotherapy (0.85 [0.78–0.93]).CONCLUSIONSThis study confirmed that type 2 diabetes was associated with poorer prognosis after incident cancer, but that the association varied according to diabetes therapy and cancer site. Metformin was associated with survival benefit both in comparison with other treatments for diabetes and in comparison with a nondiabetic population.

The D1 model best predicts the values for observed health states. The resulting preference weight estimates represent a significant enhancement of the EQ-5D's utility for health status assessment and economic analysis in the US.

This study provides U.S. population norms for self-reported health status on the EQ-5D, HUI2, and HUI3. Although these measures appeared to be valid and demonstrated similarities, health status assessed by these measures is not exactly the same.

OBJECTIVE -The aim of this study was to examine the relationship between use of metformin and sulfonylurea and mortality in new users of these agents. RESEARCH DESIGN AND METHODS -SaskatchewanHealth databases were used to examine population-based mortality rates for new users of oral antidiabetic agents. Individuals with prescriptions for sulfonylurea or metformin in [1991][1992][1993][1994][1995][1996] and no use in the year prior were identified as new users. Prescription records were prospectively followed for 1-9 years; subjects with any insulin use were excluded. Causes of death were identified based on ICD-9 codes in an electronic vital statistics database. Multivariate logistic regression and survival analyses were used to assess the differences in mortality between drug cohorts, after adjusting for potential confounding variables.RESULTS -The total study sample comprised 12,272 new users of oral antidiabetic agents; the average length of follow-up was 5.1 (SD 2.2) years. In subjects with at least 1 year of drug exposure and no insulin use, mortality rates were 750/3,033 (24.7%) for those receiving sulfonylurea monotherapy, 159/1,150 (13.8%) for those receiving metformin monotherapy, and 635/4,683 (13.6%) for those receiving combination therapy over an average 5.1 (SD 2.2) years of follow-up. The adjusted odds ratio (OR) for all-cause mortality for metformin monotherapy was 0.60 (95% CI 0.49 -0.74) compared with sulfonylurea monotherapy. Sulfonylurea plus metformin combination therapy was also associated with reduced all-cause mortality (OR 0.66, 95% CI 0.58 -0.75). Reduced cardiovascular-related mortality rates were also observed in metformin users compared with sulfonylurea monotherapy users.CONCLUSIONS -Metformin therapy, alone or in combination with sulfonylurea, was associated with reduced all-cause and cardiovascular mortality compared with sulfonylurea monotherapy among new users of these agents.