Correlation between diabetes complications severity index and actual complication severity and diabetic medication in Japanese patients with type 2 diabetes mellitus.

Decision letter for "Correlation between Diabetes Complications Severity Index and Actual Complication Severity and Diabetic Medication in Japanese Patients with Type 2 Diabetes Mellitus"

Author response for "Correlation between Diabetes Complications Severity Index and Actual Complication Severity and Diabetic Medication in Japanese Patients with Type 2 Diabetes Mellitus"

Review for "Correlation between Diabetes Complications Severity Index and Actual Complication Severity and Diabetic Medication in Japanese Patients with Type 2 Diabetes Mellitus"

Review for "Correlation between Diabetes Complications Severity Index and Actual Complication Severity and Diabetic Medication in Japanese Patients with Type 2 Diabetes Mellitus"

Decision letter for "Correlation between Diabetes Complications Severity Index and Actual Complication Severity and Diabetic Medication in Japanese Patients with Type 2 Diabetes Mellitus"

Review for "Correlation between Diabetes Complications Severity Index and Actual Complication Severity and Diabetic Medication in Japanese Patients with Type 2 Diabetes Mellitus"

Author response for "Correlation between Diabetes Complications Severity Index and Actual Complication Severity and Diabetic Medication in Japanese Patients with Type 2 Diabetes Mellitus"

Decision letter for "Correlation between Diabetes Complications Severity Index and Actual Complication Severity and Diabetic Medication in Japanese Patients with Type 2 Diabetes Mellitus"

Review for "Correlation between Diabetes Complications Severity Index and Actual Complication Severity and Diabetic Medication in Japanese Patients with Type 2 Diabetes Mellitus"

Review for "Correlation between Diabetes Complications Severity Index and Actual Complication Severity and Diabetic Medication in Japanese Patients with Type 2 Diabetes Mellitus"

Stratifying healthcare costs using the Diabetes Complication Severity Index

BackgroundThe prevalence of type 2 diabetes mellitus (T2DM) is expected to increase from 7.7% in 2017 to 8.4% in 2045 worldwide. Diabetes complications contribute to morbidity and mortality. To evaluate whether the diabetes complications severity index (DCSI) was associated with increased risks of mortality and hospitalization.MethodsA retrospective cohort study was conducted using the National Health Insurance Database (NHID) sample cohort of 1,102,047 patients (2002–2015) in Korea. Diabetes complications were evaluated at 2 years after the initial diagnosis and during the subsequent follow-up period (mean duration 6.56 ± 2.81 years). The type and severity of complications were evaluated on the basis of the International Classification of Disease Ninth (ICD-9) codes used in DCSI with 7 categories and 55 subcategories of complications. The Cox proportional hazard and Poisson regression models were used to evaluate the mortality and hospitalization rates. The incidence and relative risk of diabetes complications as well as the risk of mortality and hospitalization were the main outcome measures.ResultsA total of 27,871 patients were finally included and grouped by the number of complications present at 2 years. Four hundred ninety patients (5.37%) died without complications, 659 (7.31%) died with one complication and 1153 (11.85%) died with two or more complications. As DCSI at index date increased, the risk of additional new diabetes complications increased by 26% [relative risk (RR) 1.26, 95% CI 1.25–1.27]. The risks of mortality and hospitalization were linearly related to DCSI [hazard ratio 1.13 (95% CI 1.11–1.16), relative risk 1.04 (95% CI 1.03–1.06)].ConclusionsPatients with higher incidence and severity of diabetes complications have increased risks of mortality and hospitalization.

The dipeptidyl peptidase-4 (DPP-4) inhibitors are among the newer, yet more established, classes of diabetes medications. To compare adherence, persistence, and health care costs among patients taking DPP-4 inhibitors. Claims were extracted from Humana Medicare Advantage Prescription Drug (MAPD) or commercial plans for patients aged > 18 years with ≥ 1 prescription filled for a DPP-4 inhibitor between July 1, 2011, and March 31, 2013. The first prescription claim for a DPP-4 inhibitor established the index date and index medication; 12-month pre-index and post-index data were analyzed. The Diabetes Complications Severity Index (DCSI) was used to assess a level of baseline diabetes-related comorbidities. Adherence (proportion of days covered [PDC] ≥ 80%) and persistence (< 31-day gap) measures were compared before and after, adjusting for DCSI, pre-index insulin, age, and gender. Post-index costs (in 2013 U.S. dollars) were compared using general linear modeling (GLM) to adjust for pre-index costs, DCSI, pre-index insulin, age, and gender. Based on study criteria, 22,860 patients with MAPD coverage (17,292 sitagliptin, 4,282 saxagliptin, and 1,286 linagliptin) and 3,229 patients with commercial coverage (2,368 sitagliptin, 643 saxagliptin, and 218 linagliptin) were included. For MAPD patients, the mean age was 70-72 years, and females represented 50%-52% of patients. For commercial patients, mean age was 55-56 years, and females represented 44% of patients. Clinical indicators for patients on linagliptin showed a higher comorbidity level than sitagliptin or saxagliptin cohorts (MAPD DCSI 3.0 vs 2.4 and 2.2, P < 0.001; commercial DCSI 1.2 vs. 0.9 and 0.9, P < 0.001); a higher use of pre-index insulin (MAPD 22% vs. 15% and 14%, P < 0.001; commercial 18% vs. 11% and 10%, P = 0.003); and higher mean pre-index costs (MAPD $14,448 vs. $11,818 and $10,399, P < 0.001; commercial $13,868 vs. $9,357 and $8,223, P = 0.016). For the MAPD cohort, the unadjusted PDC was lower for linagliptin patients (67%) compared with saxagliptin (72%) or sitagliptin (72%) patients (P < 0.001). Significant differences were still seen when adjusted for covariates. Linagliptin patients were more likely to be nonpersistent (73%) than those on saxagliptin (65%) or sitagliptin (67%; P < 0.01 for adjusted and unadjusted comparisons). For the commercial population, there were no significant differences in mean PDC between the 3 groups (linagliptin 70%, saxagliptin 72%, and sitagliptin 74%; P = 0.096). Dichotomized comparisons of nonpersistence were significantly different (linagliptin 65%, saxagliptin 62%, and sitagliptin 57%; P = 0.010), although upon adjustment using a Cox proportional hazard model, no significant differences were found. When controlling for other factors, post-index adjusted health care costs were similar between the medication cohorts (MAPD: sitagliptin = $13,913, saxagliptin = $13,651, and linagliptin = $13,859; commercial: sitagliptin = $11,677, saxagliptin = $12,059, and linagliptin = $11,163; all P > 0.25). For MAPD and commercial populations, baseline patient demographics were similar between the 3 DPP-4 inhibitor groups, but the linagliptin group may have had more complex patients (higher pre-index costs, higher DCSI, and more use of insulin). For the MAPD population, patients on linagliptin were less adherent and persistent than patients taking sitagliptin or saxagliptin for all unadjusted and adjusted comparisons. For the commercial population, which was notably smaller, these differences were in the same direction, but not all were statistically significant. When controlling for baseline factors, 12-month post-index direct medical health care costs were similar between index DPP-4 inhibitors. No external funding was provided for this research. The project was done as part of internal work by Humana employees. Rascati received no compensation. None of the authors have any financial disclosures or conflicts of interests to report. Worley and Everhart are employees of Comprehensive Health Insights, a subsidiary of Humana, and Meah is an employee of Humana. Discussion of the adherence and persistence data was presented as a poster at the Academy of Managed Care Pharmacy Nexus Conference, October 2015. Cost data were presented as a poster at the International Society for Pharmacoeconomics and Outcomes Research 18th Annual European Congress, November 2015. Study concept and design were contributed by Rascati, Worley, and Meah, along with Everhart. Rascati took the lead in data collection, assisted by Meah, and data interpretation was performed by all the authors. The manuscript was written primarily by Rascati, along with Worley, Everhart, and Meah, and revised by Rascati, Everhart, and Worley, with assistance from Meah.

Concern about an increasing risk of acute pancreatitis associated with incretin-based drugs, including dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 analogs, has emerged recently. This nested case-control study examined the association between the use of DPP-4 inhibitors and acute pancreatitis using Taiwan's National Health Insurance Research Database. From a study cohort of patients with type 2 diabetes mellitus, we identified 1,957 acute pancreatitis cases (patients who had been admitted with a diagnosis of acute pancreatitis) and 7,828 age-, sex-, and cohort entry year-matched controls between 2000 and 2011. Multivariate conditional regression models were used to estimate the association between the use of DPP-4 inhibitors and acute pancreatitis. Sensitivity analyses were conducted by varying the definitions of timing of exposure to DPP-4 inhibitors. The risks of acute pancreatitis among current and past users of DPP-4 inhibitors were comparable with those of non-users (current users: adjusted odds ratio (aOR) 1.04; 95% CI [0.89-1.21]; past users: aOR 1.61 [0.93-2.77]). Similar results were found in sensitivity analyses with various definitions of "current users" of DPP-4 inhibitors. Nevertheless, the adjusted risk of acute pancreatitis was found to be increased significantly in patients with gallstone disease (aOR 5.89 [4.71-7.35]), alcohol-related disease (aOR 5.36 [4.05-7.08]), hypertriglyceridemia (aOR 1.80 [1.26-2.56]), pancreatic disease (aOR 17.29 [10.60-28.19]), and a higher Diabetes Complications Severity Index (DCSI) score (DCSI 3-4: aOR 1.49 [1.21-1.84]; DCSI≥5: aOR 1.32 [1.01-1.73]). This population-based study extends previous evidence by exploring the potential association between DPP-4 inhibitor use and the risk of acute pancreatitis in an ethnic Chinese type 2 diabetic cohort. We found that underlying diseases and severity of diabetes but not DPP-4 inhibitor use were associated with acute pancreatitis.

This research is an attempt to investigate the benefit of sodium-glucose cotransporter-2 inhibitor (SGLT2I) use in patients with diabetes mellitus (DM) for outcomes of sepsis/septic shock. We used Taiwan's national data set to identify patients and patients' characteristics to investigate sepsis/septic shock among diabetes patients who use SGLT2I compared to those who do not. We have compared the two groups for several relevant categories of potential risk factors for sepsis/septic shock and adjusted the Cox regression models accordingly. The adapted diabetes complications severity index (DCSI) was used for stratifying the advancing disease of DM. Compared to patients with DCSI = 0, patients with DCSI ≥ 2 had a significantly higher risk of sepsis/septic shock (adjusted HR = 1.52, 95% CI = 1.37-1.68). A significantly lower risk of sepsis/septic shock events was observed in the SGLT2I cohort than in the non-SGLT2I cohort with the DCSI groups [adjusted HR = 0.6 (DCSI group = 0), adjusted HR = 0.61 (DCSI group = 1), adjusted HR = 0.55 (DCSI group ≥ 2)]. Patients who received SGLT2I for a cumulative duration of ≥ 90days had a significantly lower risk of sepsis/septic shock than patients with a duration of < 90days (adjusted HR = 0.36, 95% CI = 0.34-0.39). We described a decreased risk of sepsis/septic shock among diabetic patients who took SGLT2I.