Steno Diabetes Center Copenhagen, Gentofte, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Section of Endocrinology, Yale University School of Medicine, New Haven, CT, USA.
Lancet Diabetes Endocrinol. 2022 Jan;10(1):24-34. doi: 10.1016/S2213-8587(21)00295-3. Epub 2021 Nov 29.
Chronic kidney disease and heart failure are insulin resistant states associated with a high incidence of diabetes. We assessed the effect of dapagliflozin on new-onset type 2 diabetes in a pooled analysis of patient-level data from the DAPA-CKD and DAPA-HF trials.
This study is a pooled analysis of individual participant data from two phase 3, randomised, double-blind, placebo-controlled, multicentre, clinical trials. Participants with no history of diabetes and HbA less than 6·5% (48 mmol/mol) at baseline were included in this pooled analysis. New-onset type 2 diabetes was a prespecified exploratory endpoint in both DAPA-CKD and DAPA-HF trials and is the focus of this analysis. New-onset type 2 diabetes was identified by serial trial measurements of HbA (two consecutive values ≥6·5% [≥48 mmol/mol]) or following a clinical diagnosis of diabetes between trial visits. Time to new-onset type 2 diabetes was analysed in a Cox proportional Hazards model from random assignment to end of treatment.
4003 participants (1398 [34·9%] from the DADA-CKD trial and 2605 [65·1%] from the DAPA-HF trial) were included in our analysis: 1995 (49·8%) had received dapagliflozin and 2008 (50·2%) had received placebo. Over a median follow-up of 21·2 months (IQR 16·0 to 25·4), 126 (6·3%) of 2008 patients in the placebo group (event rate 3·9 per 100 patient-years) and 85 (4·3%) of 1995 patients in the dapagliflozin group (event rate 2·6 per 100 patient-years) developed type 2 diabetes (hazard ratio 0·67 [95% CI 0·51 to 0·88]; p=0·0040). There was no heterogeneity between studies (p interaction 0·77) and there was no clear evidence that the effect of dapagliflozin varied in prespecified subgroups including sex, age, glycaemic status, BMI, glomerular filtration rate, systolic blood pressure, and baseline cardiovascular medication use. More than 90% of the participants who developed type 2 diabetes had prediabetes at baseline (HbA 5·7% to 6·4% [39 to 46 mmol/mol]). Mean HbA remained unchanged (placebo-adjusted change in the dapagliflozin group of -0·01% [95% CI -0·03 to 0·01], -0·1 mmol/mol [95% CI -0·3 to 0·1] at 12 months).
Treatment with dapagliflozin reduced the incidence of new-onset type 2 diabetes in participants with chronic kidney disease and HF without a reduction in HbA.
AstraZeneca.
慢性肾脏病和心力衰竭是胰岛素抵抗状态，与糖尿病发病率高有关。我们评估了达格列净在 DAPA-CKD 和 DAPA-HF 试验的患者水平数据的汇总分析中新发 2 型糖尿病的疗效。
这是一项来自两项 3 期、随机、双盲、安慰剂对照、多中心临床试验的患者水平数据的汇总分析。纳入的患者基线时无糖尿病史且 HbA<6.5%（48mmol/mol）。新发 2 型糖尿病是 DAPA-CKD 和 DAPA-HF 试验的预先指定的探索性终点，也是本分析的重点。新发 2 型糖尿病通过连续两次 HbA 试验测量（连续两次值≥6.5%[≥48mmol/mol]）或在试验访视期间临床诊断糖尿病确定。从随机分组到治疗结束，采用 Cox 比例风险模型分析新发 2 型糖尿病的时间。
我们的分析纳入了 4003 名参与者（DADA-CKD 试验 1398 名[34.9%]，DAPA-HF 试验 2605 名[65.1%]）：1995 名（49.8%）接受了达格列净治疗，2008 名（50.2%）接受了安慰剂治疗。中位随访 21.2 个月（IQR 16.0-25.4）时，安慰剂组 2008 名患者中有 126 名（6.3%）（事件发生率为每 100 患者年 3.9 例），达格列净组 1995 名患者中有 85 名（4.3%）（事件发生率为每 100 患者年 2.6 例）发生 2 型糖尿病（风险比 0.67[95%CI 0.51-0.88]；p=0.0040）。研究之间无异质性（p 交互=0.77），且没有明确证据表明达格列净的疗效在包括性别、年龄、血糖状态、BMI、肾小球滤过率、收缩压和基线心血管药物使用在内的预先指定亚组中存在差异。超过 90%新发 2 型糖尿病的患者基线时存在糖尿病前期（HbA 5.7%-6.4%[39-46mmol/mol]）。HbA 保持不变（达格列净组的安慰剂校正变化为-0.01%[95%CI-0.03 至 0.01]，-0.1mmol/mol[95%CI-0.3 至 0.1]，在 12 个月时）。
达格列净治疗可降低慢性肾脏病和心力衰竭患者新发 2 型糖尿病的发生率，而 HbA 无降低。
AstraZeneca。
