Dipeptidyl Peptidase-4 Inhibitors and the Risk of Gallbladder and Bile Duct Disease Among Patients with Type 2 Diabetes: A Population-Based Cohort Study.

INTRODUCTION: The use of dipeptidyl peptidase-4 (DPP-4) inhibitors may be associated with an increased risk of gallbladder and bile duct disease among patients with type 2 diabetes. METHODS: We conducted a population-based cohort study using an active comparator, new-user design. We used data from the United Kingdom Clinical Practice Research Datalink to identify patients newly treated with either a DPP-4 inhibitor or sodium-glucose cotransporter-2 (SGLT-2) inhibitor between January 2013 and December 2020. We fitted Cox proportional hazards models with propensity score fine stratification weighting to estimate the hazard ratio (HR) and its 95% confidence interval (CI) for incident gallbladder and bile duct disease associated with DPP-4 inhibitors compared to SGLT-2 inhibitors. RESULTS: DPP-4 inhibitors were associated with a 46% increased risk of gallbladder and bile duct disease (4.3 vs. 3.0 events per 1000 person-years, HR 1.46, 95% CI 1.17-1.83). At 6 months and 1 year, 745 and 948 patients, respectively, would need to be treated with DPP-4 inhibitors for one patient to experience a gallbladder or bile duct disease. CONCLUSIONS: In this population-based cohort study, the use of DPP-4 inhibitors, when compared with SGLT-2 inhibitors, was associated with a moderately increased risk of gallbladder and bile duct disease among patients with type 2 diabetes. This outcome was still quite rare with a high number needed to harm at 6 months and 1 year.

Sodium-glucose cotransporter-2 inhibitors and the risk of lung cancer among patients with type 2 diabetes.

We sought to determine whether the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors is associated with a decreased risk of incident lung cancers among patients with type 2 diabetes. We assembled a new-user, active comparator cohort of SGLT-2 inhibitor and dipeptidyl peptidase-4 (DPP-4) inhibitor users using the United Kingdom Clinical Practice Research Datalink. We fit Cox proportional hazards models with propensity score fine stratification weighting to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for incident lung cancer. Crude incidence rates were 0.94 per 1000 person-years among 69 675 SGLT-2 inhibitor users followed for a median of 2.4 years and 1.45 per 1000 person-years among 151 495 DPP-4 inhibitor users followed for a median of 3.7 years. No reduced short-term risk of lung cancer was observed among SGLT-2 inhibitor users after weighting (HR 0.96, 95% CI 0.77-1.21). Further research with a longer follow-up period may be warranted.

Association between male circumcision and human papillomavirus infection in males and females: a systematic review, meta-analysis, and meta-regression.

BACKGROUND: Previous studies have suggested a protective effect of male circumcision on human papillomavirus (HPV) infections in males, and that this protection may be conferred to their female sexual partners. OBJECTIVES: To synthesize the available evidence on the association between male circumcision and HPV infections in males and females. DATA SOURCES: We searched MEDLINE, Embase, Scopus, Cochrane, LILACS, and ProQuest Dissertations & Theses Global for records published up to 22 June 2022. STUDY ELIGIBILITY: We considered observational and experimental studies that assessed male circumcision status and HPV prevalence, incidence, or clearance in males or females for inclusion. PARTICIPANTS: Males and their female sexual partners who were tested for genital HPV infection. INTERVENTIONS: Male circumcision compared with no circumcision. THE RISK-OF-BIAS ASSESSMENT: The Newcastle-Ottawa scale was used for observational studies, and the Cochrane risk-of-bias tool was used for randomized trials. DATA SYNTHESIS: We estimated summary measures of effect and 95% CIs for the prevalence, incidence, and clearance of HPV infections in males and females using random-effects meta-analysis. We assessed the effect modification of circumcision on HPV prevalence by the penile site in males using random-effects meta-regression. RESULTS: Across 32 studies, male circumcision was associated with decreased odds of prevalent HPV infections (odds ratio, 0.45; 95% CI, 0.34-0.61), a reduced incidence rate of HPV infections (incidence rate ratio, 0.69; 95% CI, 0.57-0.83), and an increased risk of clearing HPV infections (risk ratio, 1.44; 95% CI, 1.28-1.61) at the glans penis among male subjects. Circumcision conferred greater protection against infection at the glans than the shaft (odds ratio, 0.68; 95% CI, 0.48-0.98). Females with circumcised partners were protected from all outcomes. CONCLUSIONS: Male circumcision may protect against various HPV infection outcomes, suggesting its prophylactic potential. Understanding the site-specific effects of circumcision on HPV infection prevalence has important implications for studies of HPV transmission.

Male Circumcision and Genital Human Papillomavirus (HPV) Infection in Males and Their Female Sexual Partners: Findings From the HPV Infection and Transmission Among Couples Through Heterosexual Activity (HITCH) Cohort Study.

BACKGROUND: Previous studies examining the association between male circumcision (MC) and human papillomavirus (HPV) infections have reported inconsistent results. We used data from the HPV Infection and Transmission Among Couples Through Heterosexual Activity (HITCH) cohort study to examine the association between MC and HPV infections in males and their female sexual partners. METHODS: We enrolled monogamous couples in a longitudinal study between 2005 and 2011 in Montreal, Canada. We used logistic and Poisson regression models with propensity score adjustment to estimate odds ratios (ORs) and rate ratios for the association between MC and the prevalence, transmission, and clearance of HPV infections. RESULTS: Four hundred thirteen couples were included in our study. The prevalence OR for the association between MC and baseline infections was 0.81 (95% confidence interval [CI], .56-1.16) in males and 1.05 (95% CI, .75-1.46) in females. The incidence rate ratio for infection transmission was 0.59 (95% CI, .16-2.20) for male-to-female transmission and 0.77 (95% CI, .37-1.60) for female-to-male transmission. The clearance rate ratio for clearance of infections was 0.81 (95% CI, .52-1.24). CONCLUSIONS: We found little evidence of an association between MC and HPV infection prevalence, transmission, or clearance in males and females. Further longitudinal couple-based studies are required to investigate this association.