Search

Objective: Using the 2016 Medicare Part D coverage gap as an example, we explored effects of increased out-of-pocket costs on adherence to branded dipeptidyl peptidase 4 inhibitors (DPP-4i) in patients without financial subsidies relative to subsidized patients who do not experience increased spending during the gap. We also explored seasonality of reinitiation, because discontinuers may be more likely to reinitiate in January when benefits reset., Research Design and Methods: We identified DPP-4i or sulfonylurea initiators, aged ≥66 years, from a 20% sample of 2015-2016 Medicare claims. Difference-in-differences Poisson regression was used to compare adherence before and after entering the coverage gap between nonsubsidized and subsidized patients. Among discontinuers, monthly hazard ratios (HRs) for reinitiation relative to January 2016 were derived with Cox models. As a second control, we repeated analyses using sulfonylureas, generic low-cost alternatives., Results: In 2016, 8,096 subsidized and 6,173 nonsubsidized DPP-4i initiators entered the coverage gap. For nonsubsidized patients, copayment in the coverage gap was 45% ($227 per DPP-4i prescription), and adherence decreased from 68.4% to 49.0% after gap entry. Accounting for adherence differences in subsidized patients, nonsubsidized patients demonstrated reduced adherence to DPP-4i (difference-in-difference: -16.9%; 95% CI -18.7%, -15.1%) but not sulfonylureas (-1.6%; 95% CI -3.4%, 0.2%). Reinitiation was lowest in the months before January (HR 0.4-0.5) among nonsubsidized DPP-4i patients, demonstrating a strong seasonal pattern., Conclusions: Increased out-of-pocket costs negatively affect adherence and reinitiation of branded antihyperglycemic drugs among patients without financial subsidies. Despite closure of the coverage gap, affordability remains a concern given increasing list prices for many drugs on Medicare and the growing use of deductibles and coinsurance by commercial health plans., (© 2020 by the American Diabetes Association.)

Objective: A recent study raises concerns that dipeptidyl peptidase 4 inhibitors (DPP4i) are associated with increased risk of inflammatory bowel disease (IBD). We evaluated the association between new use of DPP4i and IBD risk compared with other second-line antihyperglycemics., Research Design and Methods: We implemented an active-comparator, new-user cohort design using two U.S. administrative claims databases for commercially insured (MarketScan) and older adult (Medicare fee-for-service, 20% random sample) patients from January 2007 to December 2016. We identified patients, aged ≥18 years, who initiated DPP4i versus sulfonylureas (SUs) or initiated DPP4i versus thiazolidinediones (TZDs) and were without prior diagnosis, treatment, or procedure for IBD. The primary outcome was incident IBD, defined by IBD diagnosis preceded by colonoscopy and biopsy and followed by IBD treatment. We performed propensity score weighting to control for measured baseline confounding, estimated adjusted hazard ratios (aHRs [95% CI]) using weighted Cox proportional hazards models, and used random-effects meta-analysis models to pool aHRs across cohorts., Results: We identified 895,747 eligible patients initiating DPP4i, SU, or TZD; IBD incidence rates ranged from 11.6 to 32.3/100,000 person-years. Over a median treatment duration of 1.09-1.69 years, DPP4i were not associated with increased IBD risk across comparisons. The pooled aHRs for IBD were 0.82 (95% CI 0.41-1.61) when comparing DPP4i ( n = 161,612) to SU ( n = 310,550) and 0.76 (0.46-1.26) when comparing DPP4i ( n = 205,570) to TZD ( n = 87,543)., Conclusions: Our population-based cohort study of U.S. adults with diabetes suggests that short-term DPP4i treatment does not increase IBD risk., (© 2019 by the American Diabetes Association.)

Objective: Recent large trials yield conflicting results on the association between incretin-based therapies (IBTs) and diabetic retinopathy (DR). We examined whether IBTs increase DR risk compared with other antihyperglycemics., Research Design and Methods: We implemented an active comparator, new-user cohort design using a nationwide 20% random sample of fee-for-service U.S. Medicare beneficiaries aged 65 years or older with Parts A, B, and D coverage between 2007 and 2015. We identified the following cohorts without prior treatment for retinopathy: dipeptidyl peptidase 4 inhibitors (DPP4i) versus sulfonylureas (SU), DPP4i versus thiazolidinediones (TZD), glucagon-like peptide-1 receptor agonists (GLP1RA) versus long-acting insulin (LAI), and GLP1RA versus TZD. Primary outcome was advanced diabetic retinopathy requiring treatment (ADRRT), defined as a procedure code for retinopathy treatment. Incident diabetic retinopathy (IDR), identified by a diagnosis code, was a secondary outcome. We estimated propensity scores to balance confounders and adjusted hazard ratios (95% CI) using weighted Cox proportional hazards models., Results: We identified 213,652 eligible patients. During a median duration of 0.58 to 0.87 years across comparisons, with a rate from 6.0 to 12.8 per 1,000 person-years, IBTs were not associated with increased ADRRT or IDR risk. The adjusted hazard ratios (95% CI) for ADRRT were 0.91 (0.79-1.04) by comparing DPP4i to SU ( n = 39,292 and 87,073); 0.91 (0.75-1.11), DPP4i to TZD ( n = 51,410 and 22,231); 0.50 (0.39-0.65), GLP1RA to LAI ( n = 9,561 and 82,849); and 0.75 (0.53-1.06), GLP1RA to TZD ( n = 10,355 and 27,345)., Conclusions: Our population-based cohort study of older U.S. adults with diabetes suggests that IBTs used for approximately 1 year do not increase the DR risk., (© 2018 by the American Diabetes Association.)

Objective: To examine whether dipeptidyl peptidase 4 inhibitors (DPP-4I) increase acute pancreatitis risk in older patients and whether the association varies by age, sex, and history of cardiovascular disease (CVD)., Research Design and Methods: We conducted a cohort study of DPP-4I initiators versus thiazolidinedione (TZD) or sulfonylurea initiators using U.S. Medicare beneficiaries, 2007-2014. Eligible initiators were aged 66 years or older without history of pancreatic disease or alcohol-related diseases. Patients were followed up for hospitalization due to acute pancreatitis and censored at 90 days after treatment changes. Weighted Cox models were used to estimate the hazard ratio (HR) for acute pancreatitis. Analyses were performed overall as well as within subgroups defined by age, sex, and CVD history., Results: We found no increased risk of acute pancreatitis comparing 49,374 DPP-4I initiators to 132,223 sulfonylurea initiators (weighted HR 1.01; 95% CI 0.83-1.24) and comparing 57,301 DPP-4I initiators to 32,612 TZD initiators (weighted HR 1.11; 95% CI 0.76-1.62). Age and sex did not modify the association. Among patients with CVD, acute pancreatitis incidence was elevated in initiators of DPP-4I and sulfonylurea (2.3 and 2.4 per 1,000 person-years, respectively) but not in TZD initiators (1.5). Among patients with CVD, higher risk of acute pancreatitis was observed with DPP-4I compared with TZD (weighted HR 1.84; 95% CI 1.02-3.35) but not compared with sulfonylurea., Conclusions: Our study provides evidence that DPP-4I is not associated with an increased risk of acute pancreatitis in older adults overall. The positive association observed in patients with CVD could be due to chance or bias but merits further investigation., (© 2018 by the American Diabetes Association.)

Objective: To add to the evidence on comparative long-term effects of insulin analog glargine versus human NPH insulin on the risk for cancer., Research Design and Methods: We identified cohorts of initiators of glargine and human NPH without an insulin prescription during the prior 19 months among patients covered by the Inovalon Medical Outcomes Research for Effectiveness and Economics Registry (MORE2 Registry) between January 2003 and December 2010. Patients were required to have a second prescription of the same insulin within 180 days and to be free of cancer. We balanced cohorts on risk factors for cancer outcomes based on comorbidities, comedication, and health care use during the prior 12 months using inverse probability of treatment weighting. Incident cancer was defined as having two claims for cancer (any cancer) or the same cancer (breast, prostate, colon) within 2 months. We estimated adjusted hazard ratios (HRs) and their 95% CI using weighted Cox models censoring for stopping, switching, or augmenting insulin treatment, end of enrollment, and mortality., Results: More patients initiated glargine (43,306) than NPH (9,147). Initiators of glargine (NPH) were followed for 1.2 (1.1) years and 50,548 (10,011) person-years; 993 (178) developed cancer. The overall HR was 1.12 (95% CI 0.95-1.32). Results were consistent for breast cancer, prostate cancer, and colon cancer; various durations of treatment; and sensitivity analyses., Conclusions: Patients initiating insulin glargine rather than NPH do not seem to be at an increased risk for cancer. While our study contributes significantly to our evidence base for long-term effects, this evidence is very limited mainly based on actual dynamics in insulin prescribing.