To assess adherence to the three main drug classes in real-world patients with type 2 diabetes using biochemical urine testing, and to determine the association of nonadherence with baseline demographics, treatment targets, and complications. RESEARCH DESIGN AND METHODSAnalyses were performed of baseline data on 457 patients in the DIAbetes and LifEstyle Cohort Twente (DIALECT) study. Adherence to oral antidiabetics (OADs), antihypertensives, and statins was determined by analyzing baseline urine samples using liquid chromatography-tandem mass spectrometry. Primary outcomes were microvascular and macrovascular complications and treatment targets of LDL cholesterol, HbA 1c , and blood pressure. These were assessed cross-sectionally at baseline. RESULTSOverall, 89.3% of patients were identified as adherent. Adherence rates to OADs, antihypertensives, and statins were 95.7%, 92.0%, and 95.5%, respectively. The prevalence of microvascular (81.6% vs. 66.2%; P = 0.029) and macrovascular complications (55.1% vs. 37.0%; P = 0.014) was significantly higher in nonadherent patients. The percentage of patients who reached an LDL cholesterol target of ≤2.5 mmol/L was lower (67.4% vs. 81.1%; P = 0.029) in nonadherent patients. Binary logistic regression indicated that higher BMI, current smoking, elevated serum LDL cholesterol, high HbA 1c , presence of diabetic kidney disease, and presence of macrovascular disease were associated with nonadherence. CONCLUSIONSAlthough medication adherence of real-world type 2 diabetes patients managed in specialist care was relatively high, the prevalence of microvascular and macrovascular complications was significantly higher in nonadherent patients, and treatment targets were reached less frequently. This emphasizes the importance of objective detection and tailored interventions to improve adherence.

<p>  </p> <p><strong>Objective:</strong> To determine whether the benefits of dapagliflozin in patients with type 2 diabetes and chronic kidney disease (CKD) in the Dapagliflozin And Prevention of Adverse Outcomes in CKD trial (DAPA-CKD) varied by background glucose-lowering therapy (GLT).</p> <p><strong>Research Design and Methods:</strong> We randomized 4304 adults (including 2906 with type 2 diabetes) with baseline eGFR 25–75 mL/min/1.73m2 and urinary albumin:creatinine ratio 200–5000 mg/g to dapagliflozin 10mg or placebo once daily (NCT03036150). The primary endpoint was a composite of ≥50% eGFR decline, end-stage kidney disease, and kidney or cardiovascular death. Secondary endpoints included a kidney composite endpoint (primary composite endpoint without cardiovascular death), a cardiovascular composite endpoint (hospitalized heart failure or cardiovascular death), and all-cause mortality. In this prespecified analysis, we investigated the effects of dapagliflozin on these and other outcomes according to baseline GLT class or number of GLTs.</p> <p><strong>Results:</strong> The effects of dapagliflozin on the primary composite outcome was consistent across GLT classes and according to the number of GLTs (all interaction <em>P</em> >0.08). Similarly, we found consistent benefit of dapagliflozin compared to placebo on the secondary endpoints regardless of background GLT class or number of GLTs. The same applied to the rate of decline in estimated glomerular filtration rate and safety endpoints. Dapagliflozin reduced the initiation of insulin therapy during follow-up compared to placebo (HR 0.72 (0.54–0.96), P=0.025).</p> <p><strong>Conclusion:</strong> Dapagliflozin reduced kidney and cardiovascular events in patients with type 2 diabetes and CKD across baseline GLT class or classes in combination.</p>

OBJECTIVE To determine whether the benefits of dapagliflozin in patients with type 2 diabetes and chronic kidney disease (CKD) in the Dapagliflozin And Prevention of Adverse Outcomes in CKD trial (DAPA-CKD) varied by background glucose-lowering therapy (GLT). RESEARCH DESIGN AND METHODS We randomized 4,304 adults (including 2,906 with type 2 diabetes) with a baseline estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio of 200–5,000 mg/g to dapagliflozin 10 mg or placebo once daily (NCT03036150). The primary end point was a composite of ≥50% eGFR decline, end-stage kidney disease, and kidney or cardiovascular cause of death. Secondary end points included a kidney composite end point (primary composite end point without cardiovascular death), a cardiovascular composite end point (hospitalized heart failure or cardiovascular death), and all-cause mortality. In this prespecified analysis, we investigated the effects of dapagliflozin on these and other outcomes according to baseline GLT class or number of GLTs. RESULTS The effects of dapagliflozin on the primary composite outcome were consistent across GLT classes and according to the number of GLTs (all interaction P &gt; 0.08). Similarly, we found consistent benefit of dapagliflozin compared with placebo on the secondary end points regardless of background GLT class or number of GLTs. The same applied to the rate of decline in the eGFR rate and safety end points. Dapagliflozin reduced the initiation of insulin therapy during follow-up compared with placebo (hazard ratio 0.72; 95% CI 0.54–0.96; P = 0.025). CONCLUSIONS Dapagliflozin reduced kidney and cardiovascular events in patients with type 2 diabetes and CKD across baseline GLT class or classes in combination.

<p>  </p> <p><strong>Objective:</strong> To determine whether the benefits of dapagliflozin in patients with type 2 diabetes and chronic kidney disease (CKD) in the Dapagliflozin And Prevention of Adverse Outcomes in CKD trial (DAPA-CKD) varied by background glucose-lowering therapy (GLT).</p> <p><strong>Research Design and Methods:</strong> We randomized 4304 adults (including 2906 with type 2 diabetes) with baseline eGFR 25–75 mL/min/1.73m2 and urinary albumin:creatinine ratio 200–5000 mg/g to dapagliflozin 10mg or placebo once daily (NCT03036150). The primary endpoint was a composite of ≥50% eGFR decline, end-stage kidney disease, and kidney or cardiovascular death. Secondary endpoints included a kidney composite endpoint (primary composite endpoint without cardiovascular death), a cardiovascular composite endpoint (hospitalized heart failure or cardiovascular death), and all-cause mortality. In this prespecified analysis, we investigated the effects of dapagliflozin on these and other outcomes according to baseline GLT class or number of GLTs.</p> <p><strong>Results:</strong> The effects of dapagliflozin on the primary composite outcome was consistent across GLT classes and according to the number of GLTs (all interaction <em>P</em> >0.08). Similarly, we found consistent benefit of dapagliflozin compared to placebo on the secondary endpoints regardless of background GLT class or number of GLTs. The same applied to the rate of decline in estimated glomerular filtration rate and safety endpoints. Dapagliflozin reduced the initiation of insulin therapy during follow-up compared to placebo (HR 0.72 (0.54–0.96), P=0.025).</p> <p><strong>Conclusion:</strong> Dapagliflozin reduced kidney and cardiovascular events in patients with type 2 diabetes and CKD across baseline GLT class or classes in combination.</p>

Background: The SGLT2 inhibitor dapagliflozin reduces kidney function decline and urine albumin:creatinine ratio (UACR) on a population level. However, there is marked heterogeneity in the efficacy among individual patients. We conducted a decentralized (i.e. at home) N=1 trial to assess the effect of dapagliflozin in individual patients and the feasibility of remote data collection. Methods: Twenty patients with type 2 diabetes, UACR &gt;20 mg/g and eGFR &gt;30 mL/min/1.73m2 entered the randomized placebo-controlled double-blind N=1 trial. Patients were randomly assigned to two periods of 1-week treatment with dapagliflozin 10 mg/day and two periods of 1-week treatment with placebo in random order with 1-week wash-out periods in between. Patients collected and sent their own data with automatic uploading to an online platform and sent early morning urines 5 times/week to the laboratory for albumin and creatinine assessment. Primary outcome was UACR change from baseline (mixed effects model). The study had 80% power to detect a correlation in UACR change between first and second dapagliflozin period of 0.6. Results: Patients had a mean eGFR of 70.2 mL/min/1.73m2 and median UACR of 94.7 mg/g. During the study, dapagliflozin compared to placebo reduced albuminuria by 15.1% (95%CI 3.3 - 28.2; p=0.013). There was a marked variation in the change from baseline in UACR during dapagliflozin treatment periods (range first and second exposure -26.9 to -4.7% and -30.5 to -5.8%, respectively). The individual change in UACR during the first and second exposure correlated in the dapagliflozin periods (r=0.50; p=0.026) but not in the placebo periods (r=0.09; p=0.69). Of all scheduled urine collections (N=816), only 5 collections (0.61%) were not delivered in the laboratory. Conclusion: The individual UACR response to dapagliflozin varies among individual patients and is consistent upon re-exposure. Remote data collection was very reliable with nearly any missed urine collection. Disclosure J.Beernink: None. G.D.Laverman: Advisory Panel; AstraZeneca, Vifor Pharma Management Ltd., Boehringer Ingelheim Inc., Astellas Pharma Inc., Lilly, Other Relationship; Sanofi, AstraZeneca. H.L.Heerspink: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Bayer Inc., Eli Lilly and Company, Chinook Therapeutics Inc., CSL Behring, Gilead Sciences, Inc., George Clinical, Merck & Co., Inc., Janssen Research & Development, LLC, Traveere Pharmaceuticals, Novo Nordisk. N.Jongs: Speaker's Bureau; AstraZeneca.