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| 43. |
- Lahtela, J., et al.
(författare)
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Effect of adding dapagliflozin as an adjunct to insulin on urinary albumin-to-creatinine ratio over 52 weeks in adults with type 1 diabetes
- 2019
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: Dapagliflozin (DAPA), as an adjunct to insulin, was reported to improve glycaemic control, reduce body weight, and was well tolerated (DEPICT-1 and 2 studies) in adults with inadequately controlled type 1 diabetes (T1D; HbA1c: 58-91 mmol/mol [7.5-10.5%]).Materials and methods: In this pooled post hoc analysis of the DEPICT-1 and -2 studies, the effect of DAPA on urinary albumin-to-creatinine ratio (UACR) was evaluated in individuals with T1D with baseline micro or macroalbuminuria.Results: UACR was recorded at baseline for 548, 565, and 532 individuals treated with DAPA 5 mg, DAPA 10 mg, and placebo, respectively; baseline albuminuria was found in 80, 84, and 87 of these individuals in the respective arms. Of these 251 individuals, baseline renal function measured as estimated glomerular filtration rate (eGFR) was normal (eGFR≥90 ml min-1[1.73 m]-2) in 93, mildly impaired in (eGFR≥60-<90 ml min-1[1.73 m]-2) 131, and moderately impaired in 27 individuals (eGFR <60 ml min-1[1.73 m]-2). Changes in eGFR were similar across the treatment arms (data not shown). Dose-dependent decrease in UACR was observed with DAPA treatment at Weeks 12, 18, 24, and 52 (Figure). At Week 52, the differences in UACR between DAPA 10 mg vs placebo and DAPA 5 mg vs placebo were−31.1% (95% CI:−49.9,−5.2) and−13.3 (95% CI:−37.2, 19.8), respectively.Conclusion: Treatment with DAPA, as an adjunct to insulin, provided a dose-dependent benefit in reducing UACR, suggesting renoprotective effects in individuals with T1D with baseline albuminuria.
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| 44. |
- Landgren, Ola, et al.
(författare)
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Association of Immune Marker Changes with Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma
- 2019
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Ingår i: JAMA Oncology. - : American Medical Association (AMA). - 2374-2437 .- 2374-2445.
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Multiple myeloma is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). Risk models that estimate the risk of progression from MGUS to multiple myeloma use data from a single time point, usually the initial workup. Objective: To longitudinally investigate the alterations of serum immune markers with stable vs progressive MGUS. Design, Setting, and Participants: This prospective cross-sectional cohort study included 77469 adult participants aged 55 to 74 years in the screening arm of the National Cancer Institute Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had a diagnosis of progressing MGUS (n = 187) or stable MGUS (n = 498), including light-chain subtype, from November 1993, through December 2011. For each participant, all available serially stored prediagnostic serum samples (N = 3266) were obtained. Data analysis was performed from April 2018, to December 2018. Main Outcomes and Measures: Serum protein and monoclonal immunoglobulin levels, serum free light chains, and serum light chains within each immunoglobulin class were measured. Results: Of 685 individuals included in the study, 461 (67.3%) were men; the mean (SD) age was 69.1 (5.6) years. In cross-sectional modeling, risk factors associated with progressive MGUS were IgA isotype (adjusted odds ratio [OR], 1.80; 95% CI, 1.03-3.13; P =.04), 15 g/L or more monoclonal spike (adjusted OR, 23.5; 95% CI, 8.9-61.9; P <.001), skewed (<0.1 or >10) serum free light chains ratio (adjusted OR, 46.4; 95% CI, 18.4-117.0; P <.001), and severe immunoparesis (≥2 suppressed uninvolved immunoglobulins) (adjusted OR, 19.1; 95% Cl, 7.5-48.3; P <.001). Risk factors associated with progressive light-chain MGUS were skewed serum free light chains ratio (adjusted OR, 44.0; 95% CI, 14.2-136.3; P <.001) and severe immunoparesis (adjusted OR, 48.6; 95% CI, 9.5-248.2; P <.001). In longitudinal analysis of participants with serial samples prior to progression, 23 of 43 participants (53%) had high-risk MGUS before progression; 16 of these 23 (70%) experienced conversion from low-risk or intermediate-risk MGUS within 5 years. Similar results were found for light-chain MGUS. Conclusions and Relevance: The findings of evolving risk patterns support annual blood testing and risk assessment for patients with MGUS or light-chain MGUS.
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| 46. |
- Mathieu, C., et al.
(författare)
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Glucose Variables in Type 1 Diabetes Studies With Dapagliflozin: Pooled Analysis of Continuous Glucose Monitoring Data From DEPICT-1 and-2
- 2019
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 42:6, s. 1081-1087
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVEThis pooled analysis assessed continuous glucose monitoring (CGM) in patients with inadequately controlled type 1 diabetes (HbA(1c) >= 7.7 to <= 11.0% [>= 61 to <= 97 mmol/mol]) who received dapagliflozin as an adjunct to adjustable insulin.RESEARCH DESIGN AND METHODSCGM data were pooled from two 24-week, double-blind, randomized, phase 3 studies: Dapagliflozin Evaluation in Patients with Inadequately Controlled Type 1 Diabetes (DEPICT-1 and DEPICT-2). These studies comprised 1,591 patients receiving dapagliflozin 5 mg (n = 530), dapagliflozin 10 mg (n = 529), or placebo (n = 532).RESULTSBaseline characteristics were balanced between treatment groups. Patients receiving dapagliflozin 5 mg or 10 mg both spent more time with blood glucose in the range >3.9 to <= 10.0 mmol/L (>70 to <= 180 mg/dL) over 24 h than those receiving the placebo. The adjusted mean (SE) change from baseline at week 24 was 6.48% (0.60) with dapagliflozin 5 mg, 8.08% (0.60) with dapagliflozin 10 mg, and -2.59% (0.61) with placebo. At week 24, the mean amplitude of glucose excursion over 24 h, mean 24-h glucose values, and postprandial glucose values were also improved in patients receiving dapagliflozin over those receiving placebo. No marked differences were found at week 24 between dapagliflozin 5 or 10 mg and placebo in the percentage of glucose values <= 3.9 mmol/L (<= 70 mg/dL) or <= 3.0 mmol/L (<= 54 mg/dL) over 24 h, or in nocturnal (0000-0559 h) glucose values <= 3.9 mmol/L (<= 70 mg/dL).CONCLUSIONSIn patients with type 1 diabetes, treatment with dapagliflozin over 24 weeks improved time in range, mean glucose, and glycemic variability without increasing the time spent in the range indicating hypoglycemia.
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| 47. |
- Mathieu, C., et al.
(författare)
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Long-term efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (the DEPICT-2 study): 52-week results from a randomized controlled trial
- 2020
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Ingår i: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 22:9, s. 1516-1526
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Tidskriftsartikel (refereegranskat)abstract
- Aim To investigate the long-term efficacy and safety of dapagliflozin as an adjunct to adjustable insulin in adults with type 1 diabetes (T1D) and inadequate glycaemic control. Materials and Methods Dapagliflozin Evaluation in Patients with Inadequately Controlled Type 1 Diabetes (DEPICT-2) was a placebo-controlled, double-blind, multicentre, phase III study of adults with T1D (HbA1c 7.5%-10.5%) randomized (1:1:1) to receive dapagliflozin 5, 10 mg, or placebo. The efficacy and safety of dapagliflozin over 52 weeks were exploratory endpoints in this extension to DEPICT-2. Results Of 813 participants randomized, 88.2% completed the study. From baseline to 52 weeks, dapagliflozin 5 and 10 mg were associated with reduction in HbA1c (difference [95% CI] vs. placebo: -0.20% [-0.34, -0.06] and -0.25% [-0.38, -0.11], respectively) and adjusted mean percentage change in body weight (difference [95% CI] vs. placebo: -4.42% [-5.19, -3.64] and -4.86% [-5.63, -4.08], respectively). Serious adverse events were reported in the dapagliflozin 5, 10 mg, and placebo groups (32 [11.8%], 19 [7.0%] and 16 [5.9%], respectively). The proportion of hypoglycaemic events was similar across groups; severe hypoglycaemia was uncommon. More participants with events adjudicated as definite diabetic ketoacidosis (DKA) were in the dapagliflozin 5 and 10 mg groups versus placebo (11 [4.1%], 10 [3.7%] and 1 [0.4%], respectively); the majority of events were mild or moderate in severity and all were resolved with treatment. Conclusions Dapagliflozin led to long-term reductions in HbA1c and body weight in adults with T1D, but increased DKA risk compared with placebo.
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