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Treatment of type 2 diabetes in chronic kidney disease: a case for linagliptin in the treatment of diabetes in severe renal impairment.

ABSTRACT: Diabetes is the leading cause of chronic kidney disease, and the prevalence of both diseases is rising worldwide. Treatment of type 2 diabetes is difficult in patients with chronic kidney disease because most oral antidiabetic agents are affected by renal function and their use may be contraindicated in this patient population. Antidiabetic agents that can be used in patients with type 2 diabetes and declining renal function are needed. Incretin-based therapies, such as dipeptidyl peptidase-4 inhibitors, are a recent therapeutic class of glucose-lowering agents that may offer an effective treatment option in patients with chronic kidney disease. Within the dipeptidyl peptidase-4 class, linagliptin has a unique profile with a primarily nonrenal route of elimination, requiring no dose adjustment in patients with chronic kidney disease. This communication summarizes the findings of a 1-year, randomized, double-blind, placebo-controlled study demonstrating the favorable safety and efficacy profile of linagliptin in patients with type 2 diabetes and severe renal impairment.

SUBMITTER: Scott D

PROVIDER: S-EPMC3795009 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Treatment of type 2 diabetes in chronic kidney disease: a case for linagliptin in the treatment of diabetes in severe renal impairment.

Scott David D

Diabetes, metabolic syndrome and obesity : targets and therapy 20131002

Diabetes is the leading cause of chronic kidney disease, and the prevalence of both diseases is rising worldwide. Treatment of type 2 diabetes is difficult in patients with chronic kidney disease because most oral antidiabetic agents are affected by renal function and their use may be contraindicated in this patient population. Antidiabetic agents that can be used in patients with type 2 diabetes and declining renal function are needed. Incretin-based therapies, such as dipeptidyl peptidase-4 in ...[more]

PMID: 24124385

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Project description:ImportanceChronic kidney disease (CKD) is an often-asymptomatic complication of type 2 diabetes (T2D) that requires annual screening to diagnose. Patient-level factors linked to inadequate screening and treatment can inform implementation strategies to facilitate guideline-recommended CKD care.ObjectiveTo identify risk factors for nonconcordance with guideline-recommended CKD screening and treatment in patients with T2D.Design, setting, and participantsThis retrospective cohort study was performed at 20 health care systems contributing data to the US National Patient-Centered Clinical Research Network. To evaluate concordance with CKD screening guidelines, adults with an outpatient clinician visit linked to T2D diagnosis between January 1, 2015, and December 31, 2020, and without known CKD were included. A separate analysis reviewed prescription of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in adults with CKD (estimated glomerular filtration rate [eGFR] of 30-90 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio [UACR] of 200-5000 mg/g) and an outpatient clinician visit for T2D between October 1, 2019, and December 31, 2020. Data were analyzed from July 8, 2022, through June 22, 2023.ExposuresDemographics, lifestyle factors, comorbidities, medications, and laboratory results.Main outcomes and measuresScreening required measurement of creatinine levels and UACR within 15 months of the index visit. Treatment reflected prescription of ACEIs or ARBs and SGLT2 inhibitors within 12 months before or 6 months following the index visit.ResultsConcordance with CKD screening guidelines was assessed in 316 234 adults (median age, 59 [IQR, 50-67] years), of whom 51.5% were women; 21.7%, Black; 10.3%, Hispanic; and 67.6%, White. Only 24.9% received creatinine and UACR screening, 56.5% received 1 screening measurement, and 18.6% received neither. Hispanic ethnicity was associated with lack of screening (relative risk [RR], 1.16 [95% CI, 1.14-1.18]). In contrast, heart failure, peripheral arterial disease, and hypertension were associated with a lower risk of nonconcordance. In 4215 patients with CKD and albuminuria, 3288 (78.0%) received an ACEI or ARB; 194 (4.6%), an SGLT2 inhibitor; and 885 (21.0%), neither therapy. Peripheral arterial disease and lower eGFR were associated with lack of CKD treatment, while diuretic or statin prescription and hypertension were associated with treatment.Conclusions and relevanceIn this cohort study of patients with T2D, fewer than one-quarter received recommended CKD screening. In patients with CKD and albuminuria, 21.0% did not receive an SGLT2 inhibitor or an ACEI or an ARB, despite compelling indications. Patient-level factors may inform implementation strategies to improve CKD screening and treatment in people with T2D.

Project description:Abstract Background Cognitive impairment in chronic kidney disease (CKD) is common and underrecognized [1, 2]. Determining risk factors for cognitive impairment and whether speed of CKD progression is an important consideration may help identify cognitive impairment by nephrologists. Vascular disease is thought to underpin cognitive impairment in CKD and by segregating CKD patients with proven vascular disease, we may also be able to discover other important associations with cognitive impairment in CKD patients. Method A total of 250 patients in a UK prospective cohort of CKD patients underwent two cognitive assessments: Montreal Cognitive Assessment test and Trail Making Test. Cognitive impairment was defined using validated population cut-offs (cognitive impairment) and relative cognitive impairment. Relative cognitive impairment was defined by <1 standard deviation below the mean Z-score on any completed test. Two multivariable logistical regression models identified variables associated with cognitive impairment and realtive cognitive impairment. Results About 44 and 24.8% of patients suffered cognitive impairment and relative cognitive impairment, respectively. Depression, previous stroke and older age were significantly associated with cognitive impairment. Older age was significantly associated with relative cognitive impairment (P ≤ 0.05) and higher proteinuria and the use of psychodynamic medications were also significantly associated with relative cognitive impairment (P = 0.05). Delta estimated glomerular filtration rate (eGFR) in patients with cognitive impairment and relative cognitive impairment compared with those having normal cognition was similar (−0.77 versus −1.35 mL/min/1.73 m2/year, P = 0.34 for cognitive impairment and −1.12 versus −1.02 mL/min/1.73 m2/year, P = 0.89 for relative cognitive impairment). Conclusion Risk factors for cognitive impairment in CKD include previous stroke, depression or anxiety, higher proteinuria and prescription of psychodynamic medications. Patients with a faster eGFR decline do not represent a group of patients at increased risk of cognitive impairment.

Project description:BackgroundImmunosuppressive agents are being investigated for the treatment of chronic kidney disease (CKD) but may increase risk of infection. This was a retrospective observational study intended to evaluate the risk of hospitalized infection in patients with CKD, by estimated glomerular filtration rate (eGFR) and proteinuria status, aiming to identify the most appropriate disease stage for immunosuppressive intervention.MethodsRoutine UK primary-care and linked secondary-care data were extracted from the Clinical Practice Research Datalink. Patients with a record of CKD were identified and grouped into type 2, type 1 and nondiabetes cohorts. Time-dependent, Cox proportional hazard models were used to determine the likelihood of hospitalized infection.ResultsWe identified 97 839 patients with a record of CKD, of these 11 719 (12%) had type 2 diabetes. In these latter patients, the adjusted hazard ratios (aHR) were 1.00 (95% CI: 0.80-1.25), 1.00, 1.03 (95% CI: 0.92-1.15), 1.36 (95% CI: 0.20-1.54), 1.82 (95% CI: 1.54-2.15) and 2.41 (95% CI: 1.60-3.63) at eGFR stages G1, G2 (reference), G3a, G3b, G4 and G5, respectively; and 1.00, 1.45 (95% CI: 1.29-1.63) and 1.91 (95% CI: 1.67-2.20) at proteinuria stages A1 (reference), A2 and A3, respectively. All aHRs (except G1 and G3a) were significant, with similar patterns observed within the non-DM and overall cohorts.ConclusionseGFR and degree of albuminuria were independent markers of hospitalized infection in both patients with and without diabetes. The same patterns of hazard ratios of eGFR and proteinuria were seen in CKD patients regardless of diabetes status, with the risk of each outcome increasing with a decreasing eGFR and increasing proteinuria. Infection risk increased significantly from eGFR stage G3b and proteinuria stage A2 in type 2 diabetes. Treating type 2 DM patients with CKD at eGFR stages G1-G3a with immunosuppressive therapy may therefore provide a favourable risk-benefit ratio (G1-G3a in type 2 diabetes; G1-G2 in nondiabetes and overall cohorts) although the degree of proteinuria needs to be considered.

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Treatment of type 2 diabetes in chronic kidney disease: a case for linagliptin in the treatment of diabetes in severe renal impairment.

Publications

Treatment of type 2 diabetes in chronic kidney disease: a case for linagliptin in the treatment of diabetes in severe renal impairment.

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