Search

Aim: Sitagliptin can potentially preserve beta cell function by promoting local action of GLP-1 in the pancreas. This study examined if early addition of sitagliptin to metformin is associated with a delay in the progression of type 2 diabetes. Methods: Administrative health records from Alberta, Canada between April 1, 2008 and March 31, 2015 were used to conduct a retrospective cohort study. New metformin users were identified and included if they added sitagliptin during follow-up. Patients costarting therapy with sitagliptin and metformin were compared to those who added sitagliptin after initial metformin therapy. Potential confounding variables included age, sex, comorbidities, and cardiovascular medications at baseline. A multivariable logistic regression model was used to evaluate the association between sitagliptin addition (costart versus delayed) and insulin initiation. Change in A1c 1 year after adding sitagliptin was evaluated using a multivariable linear regression model. Results: Mean (SD) age of the 8,746 included patients was 52.1 (11.1) years, 5,655 (64.7%) were men, and 1,149 (13.1%) costarted treatment with metformin and sitagliptin. Insulin was added to the therapy of 192 (16.7%) costarters and 1,640 (21.6%) of delayed sitagliptin users (adjusted odds ratio 0.73; 95% CI: 0.62 to 0.86). The A1c change 1 year after starting sitagliptin was greater in the costarters (-2.1%; SD 2.8%) compared to delayed sitagliptin users (-1.0%; SD 1.9%). After adjusting for baseline A1c and other covariables, costarters had a greater reduction in A1c -0.56% (95% CI: -0.74% to -0.38%). Conclusions: Costarting sitagliptin with metformin is associated with a lower likelihood of disease progression in newly treated patients with type 2 diabetes compared with adding sitagliptin later in therapy. Disclosure: S.A. Campbell: None. P.E. Light: None. S.H. Simpson: None. Funding: Canadian Institutes of Health Research [ABSTRACT FROM AUTHOR]

BACKGROUND - A variety of methods are used to define exposure in pharmacoepidemiologic studies. Although each method has known biases, the relative effect of these biases on an observed association has not been fully examined. OBJECTIVE - To explore the influence of different exposure definitions on estimates, using the association between metformin and all-cause mortality as a proto-typical model. METHODS - New users of oral anti-hyperglycemic drugs were identified using administrative health databases from Alberta, Canada between 1998 and 2010. Drug exposure was described using definitions that are commonly used in observational studies. All analyses included the same covariates of age, gender, and a comorbidity score, and subjects not exposed to metformin served as the reference group. The measure of association was assessed using a Cox Proportional Hazards model for cohort studies and conditional logistic regression for case-control studies. RESULTS - We identified 64,293 new oral anti-hyperglycemic drugs users; mean age 68.9 years, 33,131 (52%) males, and 24,745 (39%) deaths during a mean follow-up of 6 years.  In adjusted models, the association between metformin and mortality ranged from 0.23 (95% CI 0.22-0.25) to 0.92 (95% CI 0.88-0.95) reduction. Most metformin exposure definitions, however, provided estimates in the 0.6-0.8 reduction range, aligning with the results of previous observational studies. CONCLUSIONS - The variety of exposure definitions tested in this analysis produced a wide range of associations between metformin and mortality risk. Therefore, pharmacoepidemiological studies should implement sensitivity analyses including at least two exposure definitions to provide more robust and potentially valid study estimates.

Objective: To characterize hypertension management in an academic family medicine clinic., Design: Cross-sectional chart review., Setting: Academic family medicine clinic in Edmonton, Alta., Participants: A total of 210 patients with 1 or more visits for hypertension during the previous 3 years., Main Outcome Measures: Patient characteristics, current antihypertensive therapies, most recent blood pressure measurements, and compelling indications according to the 2006 Canadian Hypertension Education Program recommendations., Results: A total of 185 subjects (88%) were prescribed antihypertensive medications, and 89 (42%) had controlled hypertension. Younger subjects, people with diabetes, and people not receiving antihypertensive medication therapy appeared less likely to have controlled hypertension. There were 76 subjects (36%) prescribed 1 antihypertensive medication, 65 subjects (31%) prescribed 2 antihypertensive medications, and 44 (21%) prescribed 3 or more antihypertensive medications. Angiotensin-converting enzyme inhibitors were prescribed for 51% of the subjects, diuretics for 47%, beta-blockers for 27%, calcium channel blockers for 23%, angiotensin receptor blockers for 20%, and alpha-blockers for 1%., Conclusion: Hypertension treatment and control rates in this academic family medicine clinic appear to be better than those in the general population. Following the principles of a continuous quality improvement process, this information will serve as an important foundation for identifying areas to improve hypertension management in the clinic.

Background: Although evidence-based guidelines for the treatment of type 2 diabetes mellitus provide clear recommendations for initial therapy, evidence on an optimal treatment strategy after secondary failure is unclear., Purpose: To compare the efficacy of add-on therapy using basal insulin versus an additional oral antidiabetic agent in patients with type 2 diabetes and secondary failure., Data Sources: We searched the following electronic databases from inception until June 2007: MEDLINE; EMBASE; Cochrane Central Register of Controlled Trials; Web of Science; Scopus; CINAHL; International Pharmaceutical Abstracts; Academic OneFile; PASCAL; Global Health Database; LILACS; HealthSTAR; PubMed. Reference lists of potentially relevant articles and clinical trial databases were searched, pharmaceutical manufacturers were contacted, and grey literature sources were sought., Study Selection: Randomized controlled trials (RCTs) involving subjects with type 2 diabetes with secondary failure who were randomly assigned to receive additional basal insulin therapy (insulin glargine, detemir, or NPH [neutral protamine Hagedorn]) versus another oral antidiabetic agent from any class., Data Extraction: Two reviewers independently screened articles, extracted data and assessed methodological quality. Our primary outcome was glycemic control measured by change in glycosylated hemoglobin (Hb(A1C)) and the proportion of subjects achieving a Hb(A1C) value of ≤ 7%., Data Synthesis: To compare overall efficacy between the 2 treatment strategies, change in Hb(A1C) was pooled across studies using a random-effects model and weighted mean difference (WMD). Eleven RCTs, involving 757 participants with a median age of 56 and a median known duration of diabetes of 11 years, were included in our analysis. Insulin treatment demonstrated a small but statistically significant improvement in Hb(A1C) compared with the use of an additional oral agent as add-on therapy (WMD -0.17; 95% CI [confidence interval] -0.33 to -0.02)., Limitations: The use of surrogate outcomes and the short duration of the trials makes it impossible to gain information on long-term patient-oriented outcomes. The overall quality of the studies was low, primarily in view of inadequate blinding., Conclusions: Although add-on therapy using injected insulin shows a slight benefit over an additional oral antidiabetic agent, our results indicate that basal insulin therapy and the use of an oral agent as add-on therapy produce comparable results. Non-therapeutic differences must be considered in the choice of treatment strategies. More high-quality studies with adequate safety data using more aggressive insulin titrations are needed.

Successful guideline implementation programs need to understand local barriers, incorporate multiple component interventions, and proceed within a framework of continuous quality improvement. We found few intervention studies to improve CAP guideline adherence and no controlled studies that used certain practice changes strategies that have proven effective for other conditions, such as face-to-face educational outreach, use of local opinion leaders, and individualized audit with peer-comparison feedback. Future studies in CAP management need to use rigorous study designs, use multiple evidence-based strategies to change practice, and convincingly demonstrate to front-line health care providers that the suggested interventions are safe and improve patient outcomes. Paper does not change practice, and the creation and mailing out of a practice guideline for the treatment of CAP is only the first necessary step in translating good evidence into everyday clinical practice.