Occurrence of Gastrointestinal Adverse Events Upon GLP-1 Receptor Agonist Initiation With Concomitant Metformin Use: A Post Hoc Analysis of LEADER, STEP 2, SUSTAIN-6, and PIONEER 6.

OBJECTIVE: To assess the impact of concomitant metformin use on gastrointestinal adverse events during the initiation and titration of a glucagon-like peptide 1 receptor agonist (GLP-1RA). RESEARCH DESIGN AND METHODS: Using data from four clinical trials of liraglutide and semaglutide (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results [LEADER], Semaglutide Treatment Effect in People with Obesity [STEP 2], Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes [SUSTAIN-6], and Peptide Innovation for Early Diabetes Treatment [PIONEER] 6), we compared the incidence of gastrointestinal adverse events during GLP-1RA initiation and titration in participants with and without concomitant metformin use. RESULTS: Of 16,996 participants, 12,928 (76%) were treated with metformin. Concomitant metformin use did not increase the percentage of participants who developed gastrointestinal adverse events or their severity during the observation window. Among participants experiencing gastrointestinal adverse events, metformin use did not increase study product discontinuation. Within treatment arms (GLP-1RA and placebo), a numerically higher percentage of metformin nonusers experienced gastrointestinal adverse events and discontinued the study product compared with metformin users. CONCLUSIONS: Concomitant metformin use does not increase occurrence of gastrointestinal symptoms during GLP-1RA initiation or impact GLP-1RA discontinuation.

Case study of semaglutide and cardiovascular outcomes: An application of the Causal Roadmap to a hybrid design for augmenting an RCT control arm with real-world data.

Introduction: Increasing interest in real-world evidence has fueled the development of study designs incorporating real-world data (RWD). Using the Causal Roadmap, we specify three designs to evaluate the difference in risk of major adverse cardiovascular events (MACE) with oral semaglutide versus standard-of-care: (1) the actual sequence of non-inferiority and superiority randomized controlled trials (RCTs), (2) a single RCT, and (3) a hybrid randomized-external data study. Methods: The hybrid design considers integration of the PIONEER 6 RCT with RWD controls using the experiment-selector cross-validated targeted maximum likelihood estimator. We evaluate 95% confidence interval coverage, power, and average patient time during which participants would be precluded from receiving a glucagon-like peptide-1 receptor agonist (GLP1-RA) for each design using simulations. Finally, we estimate the effect of oral semaglutide on MACE for the hybrid PIONEER 6-RWD analysis. Results: In simulations, Designs 1 and 2 performed similarly. The tradeoff between decreased coverage and patient time without the possibility of a GLP1-RA for Designs 1 and 3 depended on the simulated bias. In real data analysis using Design 3, external controls were integrated in 84% of cross-validation folds, resulting in an estimated risk difference of -1.53%-points (95% CI -2.75%-points to -0.30%-points). Conclusions: The Causal Roadmap helps investigators to minimize potential bias in studies using RWD and to quantify tradeoffs between study designs. The simulation results help to interpret the level of evidence provided by the real data analysis in support of the superiority of oral semaglutide versus standard-of-care for cardiovascular risk reduction.

Cross-sectional comparison of quality of life and illness intrusiveness in patients who are treated with nocturnal home hemodialysis versus peritoneal dialysis.

BACKGROUND AND OBJECTIVES: Nocturnal home hemodialysis provides excellent biochemical and metabolic control of uremia; however, extensive training is necessary and technical barriers exist for intensive home hemodialysis compared with the relative simplicity of peritoneal dialysis. It was hypothesized that nocturnal home hemodialysis is associated with improved quality of life but higher illness intrusiveness compared with peritoneal dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: All home dialysis patients at the University Health Network were approached to complete the Kidney Disease Quality of Life-Short Form, Beck Depression Inventory, and Illness Intrusiveness Survey during February to June 2006. RESULTS: Sixty-nine percent of all eligible patients completed the survey. Of the three domains derived from the Kidney Disease Quality of Life-Short Form, there was no difference in the kidney disease component summary, physical component summary, and the mental component summary between the two groups. There was a trend toward better sexual function in the nocturnal home hemodialysis group; however, nocturnal home hemodialysis patients experienced less social support than the peritoneal dialysis group. There was no difference between the nocturnal home hemodialysis and peritoneal dialysis patients with respect to the Beck Depression Index. Total illness intrusiveness score was similar between the nocturnal home hemodialysis and peritoneal dialysis patients. CONCLUSIONS: This study suggests that nocturnal home hemodialysis is not perceived as a more intrusive treatment and demonstrates that patients who are on peritoneal dialysis have similar perceived symptomatic control of their kidney disease.

Internet use by end-stage renal disease patients.

Information on the prevalence and predictors of use of the Internet by patients can be applied to the design and promotion of healthcare Internet technologies. To our knowledge, few studies on Internet use by end-stage renal disease (ESRD) patients have been reported. The objectives of this study are to ascertain the prevalence and predictors of Internet use by ESRD patients among different dialysis modalities. A questionnaire surveying Internet use was delivered in person to 199 conventional hemodialysis patients (57 returned), and mailed to 170 peritoneal dialysis (PD) patients (42 returned), and 65 nocturnal home hemodialysis (NHD) patients (43 returned). Of the respondents, most (58%) have used the Internet to find information on their health condition. The strong majority (76%) of these patients have easy access to the Internet. A higher proportion of NHD patients (86%) used the Internet compared with the PD patients (60%) (p=0.02). Internet use was found to be more prevalent with younger (p<0.001), more educated (p=0.001), and Canadian-born patients (p=0.005). The high prevalence of Internet use and easy access to the Internet by ESRD patients suggest that future Internet information and communication systems for healthcare management in ESRD will likely be well adopted by this patient population.