2022 新增：
如圖 10.1 所示，建議採用綜合方法來降低糖尿病相關並發症的風險。 包括多種同時基於證據的護理方法的治療將互補降低微血管、腎臟、神經和心血管並發症的風險。 血糖、血壓和血脂的管理以及將特定療法與心血管和腎臟結果的益處相結合（視情況而定）被認為是降低糖尿病全球風險的基本要素。
As depicted in Fig. 10.1, a comprehensive approach to the reduction in risk of diabetes-related complications is recommended. Therapy that includes multiple, concurrent evidence-based approaches to care will provide complementary reduction in the risks of microvascular, kidney, neurologic, and cardiovascular complications. Management of glycemia, blood pressure, and lipids and the incorporation of specific therapies with cardiovascular and kidney outcomes benefit (as individually appropriate) are considered fundamental elements of global risk reduction in diabetes.
Hypertension/Blood Pressure Control
2021 vs 2022：
每次常規臨床就診時都應測量血壓。 在可能的情況下，發現血壓升高（≥140/90 mmHg）的患者應使用多個讀數（包括單獨一天的測量值）確認血壓，以診斷高血壓。
10.1 Blood pressure should be measured at every routine clinical visit. When possible, patients found to have elevated blood pressure (≥140/90 mmHg) should have blood pressure confirmed using multiple readings, including measurements on a separate day, to diagnose hypertension.
2022 新增：
血壓≥180/110 mmHg 的心血管疾病患者一次就診即可診斷為高血壓。 E
A Patients with blood pressure ≥180/110 mmHg and cardiovascular disease could be diagnosed with hypertension at a single visit. E
2021 vs 2022：
應由受過培訓的人員在每次常規臨床就診時測量血壓，並應遵循為一般人群制定的指南：在坐姿測量，雙腳放在地板上，手臂支撐在心髒水平，休息 5 分鐘後。 袖帶尺寸應適合上臂圍。 升高的值最好在另一天確認； 然而，對於心血管疾病和血壓≥180/110 mmHg 的患者，一次就診即可診斷高血壓是合理的 (18)。
Blood pressure should be measured at every routine clinical visit by a trained individual and should follow the guidelines established for the general population: measurement in the seated position, with feet on the floor and arm supported at heart level, after 5 min of rest. Cuff size should be appropriate for the upper-arm circumference. Elevated values should preferably be confirmed on a separate day; however, in patients with cardiovascular disease and blood pressure ≥180/110 mmHg, it is reasonable to diagnose hypertension at a single visit (18). (2022 新增）
Individualization of Treatment Targets
2022 新增：
然而，在 ACCORD BP 中，發現強化降壓降低了心血管事件的風險，而與接受標準血糖控制的患者的基線舒張壓無關 (43)。 因此，在其他標準護理的背景下，低舒張壓的存在不一定是加強血壓管理的禁忌症。
However, in ACCORD BP, it was found that intensive blood pressure lowering decreased the risk of cardiovascular events irrespective of baseline diastolic blood pressure in patients who also received standard glycemic control (43). Therefore, the presence of low diastolic blood pressure is not necessarily a contraindication to more intensive blood pressure management in the context of otherwise standard care.
Lifestyle Intervention
2022 新增：
Use of internet or mobile-based digital platforms to reinforce healthy behaviors may be considered as a component of care, as these interventions have been found to enhance the efficacy of medical therapy for hypertension (52,53).
Classes of Antihypertensive Medications.
2022 新增：
在接受 ACEI 或 ARB 治療的患者中，當腎功能下降至 eGFR <30 mL/min/1.73 m2 時繼續使用這些藥物可能會提供心血管益處，而不會顯著增加終末期腎病的風險 (65 ）。
In patients receiving ACE inhibitor or ARB therapy, continuation of those medications as kidney function declines to estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 may provide cardiovascular benefit without significantly increasing the risk of end-stage kidney disease (65).
Bedtime Dosing.
2021:
越來越多的證據表明，夜間血壓不下降與 ASCVD 的發生率之間存在關聯。 一項隨機臨床試驗的薈萃分析發現，在控制血壓方面，晚間與早間服用降壓藥相比有少許益處，但沒有關於臨床效果的數據（67）。 在隨後的一項隨機對照試驗的兩個亞組分析中，將至少一種抗高血壓藥物轉移到就寢時間顯著減少了心血管事件，但結果基於少數事件（68）。
Growing evidence suggests that there is an association between the absence of nocturnal blood pressure dipping and the incidence of ASCVD. A meta-analysis of randomized clinical trials found a small benefit of evening versus morning dosing of antihypertensive medications with regard to blood pressure control but had no data on clinical effects (67). In two subgroup analyses of a single subsequent randomized controlled trial, moving at least one antihypertensive medication to bedtime significantly reduced cardiovascular events, but results were based on a small number of events (68).
2022 修正：
儘管先前對隨機臨床試驗的分析發現，晚上服用降壓藥優於早上服用抗高血壓藥物 (72,73)，但這些結果並未在隨後的試驗中重現。 因此，不推薦在睡前優先使用降壓藥（73a）
Although prior analyses of randomized clinical trials found a benefit to evening versus morning dosing of antihypertensive medications (72,73), these results have not been reproduced in subsequent trials. Therefore, preferential use of antihypertensives at bedtime is not recommended (73a).
Statin TreatmentSecondary Prevention
2021 vs 2022:
10.24 對於使用特定標準被認為具有極高風險的糖尿病和動脈粥樣硬化性心血管疾病患者，如果在最大耐受 statin 劑量下 LDL-C ≥70 mg/dL，則考慮增加額外的降低 LDL 治療（如 ezetimibe 或 PCSK9 抑製劑）。 由於成本較低，可能首選 ezetimibe。
10.24 For patients with diabetes and atherosclerotic cardiovascular disease considered very high risk using specific criteria, if LDL cholesterol is ≥70 mg/dL on maximally tolerated statin dose, consider adding additional LDL-lowering therapy (such as ezetimibe or PCSK9 inhibitor). A Ezetimibe may be preferred due to lower cost. (2022 刪除）
Secondary Prevention (Patients With ASCVD)
2021 vs 2022:
對於正在接受高強度（和最大耐受）statin 藥物治療且 LDL-c ≥70 mg/dL 的高危 ASCVD 患者，在臨床醫生與患者討論以下內容後，可以考慮加用非statin 藥物降低 LDL 治療。 淨收益、安全性和成本。 儘管 PCSK9 抑製劑治療的成本隨著時間的推移而降低，但許多患者可能更喜歡成本較低的 ezetimibe。
For very high-risk patients with ASCVD who are on high-intensity (and maximally tolerated) statin therapy and have an LDL cholesterol ≥70 mg/dL, the addition of nonstatin LDL-lowering therapy can be considered following a clinician-patient discussion about the net benefit, safety, and cost. Although the costs of PCSK9 inhibitor therapy have decreased over time, the lower cost of ezetimibe may be preferred by many patients. (2022 新增）
Statins and PCSK9 Inhibitors
2021 vs 2022：
在 2.2 年的中位隨訪期間，心血管死亡、心肌梗塞、中風、心絞痛住院或血管重建的複合結局分別發生在安慰劑組和 evolocumab 組，為 11.3% 和 9.8%，相對風險為 15% 減少（P < 0.001）。 心血管死亡、心肌梗塞、中風的綜合終點降低了 20%，從 7.4% 降至 5.9%（P < 0.001）。
Evolocumab 治療還顯著減少了所有中風（1.5% 對 1.9%；HR 0.79 [95% CI 0.66–0.95]；P = 0.01）和缺血性中風（1.2% 對 1.6%；HR 0.75 [95% CI 0.62–0.92） ]；P = 0.005)，在基線時有或沒有缺血性卒中病史的患者中的發現是一致的 (110)。(2022 新增）
重要的是，在預先指定的糖尿病患者亞組中觀察到了類似的益處，該亞組包括 11,031 名患者（佔試驗的 40%）（104）
During the median follow-up of 2.2 years, the composite outcome of cardiovascular death, MI, stroke, hospitalization for angina, or revascularization occurred in 11.3% vs. 9.8% of the placebo and evolocumab groups, respectively, representing a 15% relative risk reduction (P < 0.001). The combined end point of cardiovascular death, MI, or stroke was reduced by 20%, from 7.4% to 5.9% (P < 0.001).
Evolocumab therapy also significantly reduced all strokes (1.5% vs. 1.9%; HR 0.79 [95% CI 0.66–0.95]; P = 0.01) and ischemic stroke (1.2% vs. 1.6%; HR 0.75 [95% CI 0.62–0.92]; P = 0.005) in the total population, with findings being consistent in patients with or without a history of ischemic stroke at baseline (110). (2022 新增）
Importantly, similar benefits were seen in a prespecified subgroup of patients with diabetes, comprising 11,031 patients (40% of the trial) (104).
2022 新增：Statin 類藥物和 Bempedoic Acid
Bempedoic acid 是一種新型 LDL 膽固醇降低劑，可作為飲食和最大耐受Statin 類藥物治療的輔助藥物，用於治療需要額外降低 LDL-C 的雜合子家族性高膽固醇血症或已確診的動脈粥樣硬化性心血管疾病的成人。 一項匯總分析表明，與安慰劑相比，Bempedoic Acid 治療可將 LDL-C 水平降低約 23% (114)。 目前，還沒有完成的試驗證明使用這種藥物對心血管結果有益； 然而，對於不能使用或耐受其他基於證據的 LDL 膽固醇降低方法或其他療法效果不佳的患者，可以考慮使用該藥物 (115)。
Statins and Bempedoic Acid
Bempedoic acid is a novel LDL cholesterol–lowering agent that is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL cholesterol. A pooled analysis suggests that bempedoic acid therapy lowers LDL cholesterol levels by about 23% compared with placebo (114). At this time, there are no completed trials demonstrating a cardiovascular outcomes benefit to use of this medication; however, this agent may be considered for patients who cannot use or tolerate other evidence-based LDL cholesterol–lowering approaches, or for whom those other therapies are inadequately effective (115).
Treatment of Other Lipoprotein Fractions or Targets
2022 新增：
例如，在患有動脈粥樣硬化性血脂異常和高風險 CV 的病患（其中 70% 患有糖尿病），使用 statin 時再加入 4g n-3 脂肪酸的 EPA, 和 DHA, 並未降低主要不良心血管事件的風險（118）。
As an example, the addition of 4 g per day of a carboxylic acid formulation of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (n-3 carboxylic acid) to statin therapy in patients with atherogenic dyslipidemia and high cardiovascular risk, 70% of whom had diabetes, did not reduce the risk of major adverse cardiovascular events compared with the inert comparator of corn oil (118).
Aspirin Use in People <50 Years of AgeAspirin Dosing
2022 新增：
在 ADAPTABLE試驗中，已確診的心血管疾病患者（其中 38% 患有糖尿病）給予 81mg vs. 325mg aspirin，在心血管事件或大出血方面沒有顯著差異。 (153)。
In the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness) trial of patients with established cardiovascular disease, 38% of whom had diabetes, there were no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily (153).
Indications for P2Y12 Receptor Antagonist Use
2022 新增：
然而，與冠狀動脈支架置入術後，繼續雙抗血小板治療 vs. 早期停用aspirin 可能會降低出血風險，而不會相應增加死亡和缺血事件的風險，如 TWILIGHT 預先指定糖尿病患者的分析和最近的一項薈萃分析（163,164）。
However, early aspirin discontinuation compared with continued dual antiplatelet therapy after coronary stenting may reduce the risk of bleeding without a corresponding increase in the risks of mortality and ischemic events, as shown in a prespecified analysis of patients with diabetes enrolled in the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial and a recent meta-analysis (163,164).
Combination Antiplatelet and Anticoagulation Therapy
2021 vs 2022：
應與符合條件的患者徹底討論雙重抗血小板或抗血小板加抗凝治療策略的風險和益處，並應使用共同決策來確定適合個體的治療方法。 降低心血管風險這一領域正在迅速發展，對於具有不同類型和心血管並發症情況的患者的最佳護理定義也在迅速發展。
The risks and benefits of dual antiplatelet or antiplatelet plus anticoagulant treatment strategies should be thoroughly discussed with eligible patients, and shared decision-making should be used to determine an individually appropriate treatment approach. This field of cardiovascular risk reduction is evolving rapidly, as are the definitions of optimal care for patients with differing types and circumstances of cardiovascular complications. (2022 新增）
Cardiovascular DiseaseScreening Recommendations
2022 新增：
10.42c 在患有 2 型糖尿病和確定的 ASCVD 或存在多種 ASCVD 危險因素的患者中，聯合治療具有已證實的心血管益處的 SGLT2 抑製劑和已證實有心血管益處的 GLP-1 RA 可能 考慮額外降低心血管和腎臟不良事件的風險。 A
10.42c In patients with type 2 diabetes and established atherosclerotic cardiovascular disease or multiple risk factors for atherosclerotic cardiovascular disease, combined therapy with a sodium–glucose cotransporter 2 inhibitor with demonstrated cardiovascular benefit and a glucagon-like peptide 1 receptor agonist with demonstrated cardiovascular benefit may be considered for additive reduction in the risk of adverse cardiovascular and kidney events. A
SGLT2 Inhibitor Trials
2022 修正 新增：
DAPA-HF, DAPA-CHF, EMPEROR-Reduced, VERTIS CV, SCORED trials
In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial (190), 4,304 patients with chronic kidney disease (UACR 200–5,000 mg/g and eGFR 25–75 mL/min/1.73 m2), with or without diabetes, were randomized to dapagliflozin 10 mg daily or placebo. The primary outcome was a composite of sustained decline in eGFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes. Over a median follow-up period of 2.4 years, a primary outcome event occurred in 9.2% of participants in the dapagliflozin group and 14.5% of those in the placebo group. The risk of the primary composite outcome was significantly lower with dapagliflozin therapy compared with placebo (HR 0.61 [95% CI 0.51–0.72]), as were the risks for a renal composite outcome of sustained decline in eGFR of at least 50%, end-stage kidney disease, or death from renal causes (HR 0.56 [95% CI 0.45–0.68]), and a composite of cardiovascular death or hospitalization for heart failure (HR 0.71 [95% CI 0.55–0.92]). The effects of dapagliflozin therapy were similar in patients with and without type 2 diabetes.
Results of the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial and the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure and a Reduced Ejection Fraction (EMPEROR-Reduced), which assessed the effects of dapagliflozin and empagliflozin, respectively, in patients with established heart failure (191), are described below in glucose-lowering therapies and heart failure.
The Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial (VERTIS CV) (192) was a randomized, double-blind trial that established the effects of ertugliflozin versus placebo on cardiovascular outcomes in 8,246 patients with type 2 diabetes and established ASCVD. Participants were assigned to the addition of 5 mg or 15 mg of ertugliflozin or to placebo once daily to background standard care. Study participants had a mean age of 64.4 years and a mean duration of diabetes of 13 years at baseline and were followed for a median of 3.0 years. VERTIS CV met the prespecified criteria for noninferiority of ertugliflozin to placebo with respect to the primary outcome of major adverse cardiovascular events (11.9% in the pooled ertugliflozin group and 11.9% in the placebo group; HR 0.97 [95% CI 0.85–1.11]; P < 0.001). Ertugliflozin was not superior to placebo for the key secondary outcomes of death from cardiovascular causes or hospitalization for heart failure; death from cardiovascular causes; or the composite of death from renal causes, renal replacement therapy, or doubling of the serum creatinine level. The hazard ratio for a secondary outcome of hospitalization for heart failure (ertugliflozin vs. placebo) was 0.70 [95% CI 0.54–0.90], consistent with findings from other SGLT2 inhibitor cardiovascular outcomes trials.
Sotagliflozin, an investigational SGLT1 and SGLT2 inhibitor that lowers glucose via delayed glucose absorption in the gut in addition to increasing urinary glucose excretion, has been evaluated in the Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk (SCORED) trial (193). A total of 10,584 patients with type 2 diabetes, chronic kidney disease, and additional cardiovascular risk were enrolled in SCORED and randomized to sotagliflozin 200 mg once daily (uptitrated to 400 mg once daily if tolerated) or placebo. SCORED ended early due to a lack of funding; thus, changes to the prespecified primary end points were made prior to unblinding to accommodate a lower than anticipated number of end point events. The primary end point of the trial was the total number of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure. After a median of 16 months of follow-up, the rate of primary end point events was reduced with sotagliflozin (5.6 events per 100 patient-years in the sotagliflozin group and 7.5 events per 100 patient-years in the placebo group [HR 0.74 (95% CI 0.63–0.88); P < 0.001]). Sotagliflozin also reduced the risk of the secondary end point of total number of hospitalizations for heart failure and urgent visits for heart failure (3.5% in the sotagliflozin group and 5.1% in the placebo group; HR 0.67 [95% CI 0.55–0.82]; P < 0.001) but not the secondary end point of deaths from cardiovascular causes. No significant between-group differences were found for the outcome of all-cause mortality or for a composite renal outcome comprising the first occurrence of long-term dialysis, renal transplantation, or a sustained reduction in eGFR. In general, the adverse effects of sotagliflozin were similar to those seen with use of SGLT2 inhibitors, but they also included an increased rate of diarrhea potentially related to the inhibition of SGLT1.
GLP-1 Receptor Agonist Trials
2021：
It is unknown whether use of both classes of drugs will provide an additive cardiovascular outcomes benefit.
2022 修正：
新出現的數據表明，使用這兩類藥物將提供額外的心血管和腎臟結果益處；因此，可以考慮使用 SGLT2 抑製劑和 GLP-1 RA 的聯合治療來提供與這些類別的藥物相關的互補結果益處。支持這種方法的證據包括 AMPLITUDE-O（Efpeglenatide 對心血管結果的影響）的結果，這是最近完成的 2 型糖尿病和心血管或腎臟疾病患者的結果試驗，加上至少一個其他風險因素隨機分配到研究 GLP -1 受體激動劑 efpeglenatide 或安慰劑 (205)。隨機化按當前或潛在使用 SGLT2 抑製劑治療進行分層，最終有超過 15% 的試驗參與者使用該類別。在 1.8 年的中位隨訪期間，Efpeglenatide 治療將發生主要不良心血管事件的風險降低了 27%，將復合腎臟結局事件的風險降低了 32%。重要的是，Efpeglenatide 的作用沒有因使用 SGLT2 抑製劑而改變，這表明 GLP-1 受體激動劑的有益作用獨立於 SGLT2 抑製劑治療所提供的作用。
Emerging data suggest that use of both classes of drugs will provide an additive cardiovascular and kidney outcomes benefit; thus, combination therapy with an SGLT2 inhibitor and a GLP-1 receptor agonist may be considered to provide the complementary outcomes benefits associated with these classes of medication. Evidence to support such an approach includes findings from AMPLITUDE-O (Effect of Efpeglenatide on Cardiovascular Outcomes), the recently completed outcomes trial of patients with type 2 diabetes and either cardiovascular or kidney disease plus at least one other risk factor randomized to the investigational GLP-1 receptor agonist efpeglenatide or placebo (205). Randomization was stratified by current or potential use of SGLT2 inhibitor therapy, a class ultimately used by >15% of the trial participants. Over a median follow-up of 1.8 years, efpeglenatide therapy reduced the risk of incident major adverse cardiovascular events by 27% and of a composite renal outcome event by 32%. Importantly, the effects of efpeglenatide did not vary by use of SGLT2 inhibitors, suggesting that the beneficial effects of the GLP-1 receptor agonist were independent of those provided by SGLT2 inhibitor therapy.
Glucose-Lowering Therapies and Heart Failure
2021 vs 2022：
多達 50% 的 2 型糖尿病患者可能會出現心衰竭 (206)。 這些情況都與發病率和死亡率增加有關，通常同時發生並獨立導致不良後果（207）。 需要降低這些風險的策略，在確定糖尿病患者的治療方案時，應仔細考慮降糖藥物與心衰竭相關的風險和益處，無論是確定心衰竭還是發生心衰竭的高風險患者 . (2022 新增)
As many as 50% of patients with type 2 diabetes may develop heart failure (206). These conditions, which are each associated with increased morbidity and mortality, commonly coincide and independently contribute to adverse outcomes (207). Strategies to mitigate these risks are needed, and the heart failure–related risks and benefits of glucose-lowering medications should be considered carefully when determining a regimen of care for patients with diabetes and either established heart failure or high risk for the development of heart failure.
2021 vs 2022：
對 2 型糖尿病和心衰竭患者的觀察性研究表明，metformin 使用者比使用其他抗高血糖藥物治療的患者有更好的結果 (212)； 然而，尚未在心衰竭患者中進行metformin 治療的隨機試驗。 只要腎功能保持在推薦使用範圍內，metformin 可用於治療穩定型心衰竭患者的高血糖症 (213)。
Observational studies of patients with type 2 diabetes and heart failure suggest that metformin users have better outcomes than patients treated with other antihyperglycemic agents (212); however, no randomized trial of metformin therapy has been conducted in patients with heart failure. (2022 新增）Metformin may be used for the management of hyperglycemia in patients with stable heart failure as long as kidney function remains within the recommended range for use (213).
2022 新增 EMPEROR-Reduced，SOLOIST-WHF，EMPEROR-Preserved
EMPEROR-Reduced assessed the effects of empagliflozin 10 mg once daily versus placebo on a primary composite outcome of cardiovascular death or hospitalization for worsening heart failure in a population of 3,730 patients with NYHA class II, III, or IV heart failure and an ejection fraction of 40% or less (217). At baseline, 49.8% of participants had a history of diabetes. Over a median follow-up of 16 months, those in the empagliflozin-treated group had a reduced risk of the primary outcome (HR 0.75 [95% CI 0.65–0.86]; P < 0.001) and fewer total hospitalizations for heart failure (HR 0.70 [95% CI 0.58–0.85]; P < 0.001). The effect of empagliflozin on the primary outcome was consistent irrespective of diabetes diagnosis at baseline. The risk of a prespecified renal composite outcome (chronic dialysis, renal transplantation, or a sustained reduction in eGFR) was lower in the empagliflozin group than in the placebo group (1.6% in the empagliflozin group vs. 3.1% in the placebo group; HR 0.50 [95% CI 0.32–0.77]).
Additional data are accumulating regarding the effects of SGLT inhibition in patients hospitalized for acute decompensated heart failure and in heart failure patients with HFpEF. As an example, the investigational SGLT1 and SGLT2 inhibitor sotagliflozin has also been studied in the Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure (SOLOIST-WHF) trial (218). In SOLOIST-WHF, 1,222 patients with type 2 diabetes who were recently hospitalized for worsening heart failure were randomized to sotagliflozin 200 mg once daily (with uptitration to 400 mg once daily if tolerated) or placebo either before or within 3 days after hospital discharge. Patients were eligible if hospitalized for signs and symptoms of heart failure (including elevated natriuretic peptide levels) requiring treatment with intravenous diuretic therapy. Exclusion criteria included end-stage heart failure or recent acute coronary syndrome or intervention, or an eGFR <30 mL/min/1.73 m2). Patients were required to be clinically stable prior to randomization, defined as no use of supplemental oxygen, a systolic blood pressure ≥100 mmHg, and no need for intravenous inotropic or vasodilator therapy other than nitrates. Similar to SCORED, SOLOIST-WHF ended early due to a lack of funding, resulting in a change to the prespecified primary end point prior to unblinding to accommodate a lower than anticipated number of end point events. At a median follow-up of 9 months, the rate of primary end point events (the total number of cardiovascular deaths and hospitalizations and urgent visits for heart failure) was lower in the sotagliflozin group than in the placebo group (51.0 vs. 76.3; HR 0.67 [95% CI 0.52–0.85]; P < 0.001). No significant between-group differences were found in the rates of cardiovascular death or all-cause mortality. Both diarrhea (6.1% vs. 3.4%) and severe hypoglycemia (1.5% vs. 0.3%) were more common with sotagliflozin than with placebo. The trial was originally also intended to evaluate the effects of SGLT inhibition in patients with HFpEF, and ultimately no evidence of heterogeneity of treatment effect by ejection fraction was noted. However, the relatively small percentage of such patients enrolled (only 21% of participants had ejection fraction >50%) and the early termination of the trial limited the ability to determine the effects of sotagliflozin in HFpEF specifically. Additional data regarding the impact of SGLT2 inhibitor therapy in patients with HFpEF will soon be available from EMPEROR-Preserved, the empagliflozin outcome trial of nearly 6,000 patients with symptomatic heart failure with preserved ejection fraction (left ventricular ejection fraction >40%) (219), with or without type 2 diabetes.