[
  {
    "id": "test-001",
    "title": "Efficacy and Safety of Empagliflozin in Patients with Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial",
    "abstract": "Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors represent a novel class of glucose-lowering agents. We evaluated the efficacy and safety of empagliflozin in patients with type 2 diabetes. Methods: In this 24-week, randomized, double-blind, placebo-controlled trial, we randomly assigned 800 adults with type 2 diabetes and inadequate glycemic control (HbA1c 7.0-10.0%) to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily. The primary endpoint was change in HbA1c from baseline. Secondary endpoints included body weight, systolic blood pressure, and adverse events. Results: Both empagliflozin doses significantly reduced HbA1c compared with placebo (10 mg: -0.74%, 25 mg: -0.85%, placebo: -0.13%; P<0.001). Empagliflozin also reduced body weight and systolic blood pressure. The incidence of hypoglycemia was low and similar across groups. Conclusions: Empagliflozin significantly improved glycemic control in patients with type 2 diabetes with acceptable safety profile.",
    "authors": "Zinman B, Wanner C, Lachin JM, et al.",
    "journal": "New England Journal of Medicine",
    "publicationYear": 2015,
    "doi": "10.1056/NEJMoa1504720",
    "expectedDecision": "include",
    "rationale": "明确的RCT研究，SGLT2抑制剂治疗2型糖尿病，有安慰剂对照，主要结局为HbA1c，完全符合PICO标准"
  },
  {
    "id": "test-002",
    "title": "Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes",
    "abstract": "Background: The cardiovascular safety of ertugliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has not been established. Methods: We randomly assigned 8246 patients with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease to receive ertugliflozin (5 mg or 15 mg) or placebo, in addition to standard care. The primary outcome was major adverse cardiovascular events (MACE), defined as death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results: During a median follow-up of 3.5 years, MACE occurred in 11.9% of patients in the ertugliflozin group and 11.9% of patients in the placebo group (hazard ratio, 0.97; 95% CI, 0.85-1.11; P<0.001 for noninferiority). Ertugliflozin was associated with lower rates of hospitalization for heart failure. The rates of adverse events were similar in the two groups. Conclusions: Among patients with type 2 diabetes and atherosclerotic cardiovascular disease, ertugliflozin was noninferior to placebo with respect to major adverse cardiovascular events.",
    "authors": "Cannon CP, Pratley R, Dagogo-Jack S, et al.",
    "journal": "New England Journal of Medicine",
    "publicationYear": 2020,
    "doi": "10.1056/NEJMoa2004967",
    "expectedDecision": "include",
    "rationale": "大规模RCT，SGLT2抑制剂，有安慰剂对照，评估心血管结局，符合标准"
  },
  {
    "id": "test-003",
    "title": "Systematic Review and Meta-Analysis of SGLT2 Inhibitors in Type 2 Diabetes: A Comprehensive Assessment",
    "abstract": "Objective: To systematically review and meta-analyze the efficacy and safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes. Methods: We searched PubMed, Embase, and the Cochrane Library through December 2022. We included randomized controlled trials comparing SGLT2 inhibitors with placebo or active comparators in adults with type 2 diabetes. Primary outcomes were glycemic control (HbA1c), body weight, and cardiovascular events. Results: We identified 142 eligible trials involving 87,562 participants. SGLT2 inhibitors significantly reduced HbA1c (mean difference -0.68%, 95% CI -0.73 to -0.63), body weight (-1.9 kg), and systolic blood pressure (-4.2 mmHg). The incidence of major adverse cardiovascular events was reduced by 11%. Conclusions: SGLT2 inhibitors demonstrate consistent benefits in glycemic control, weight reduction, and cardiovascular outcomes.",
    "authors": "McGuire DK, Shih WJ, Cosentino F, et al.",
    "journal": "Diabetes Care",
    "publicationYear": 2023,
    "doi": "10.2337/dc22-1234",
    "expectedDecision": "exclude",
    "rationale": "这是系统综述/Meta分析，不是原始研究，应排除"
  },
  {
    "id": "test-004",
    "title": "Dapagliflozin Improves Cardiac Function in Diabetic Rats: An Experimental Study",
    "abstract": "Background: The cardioprotective effects of dapagliflozin in diabetes remain unclear. We investigated the effects of dapagliflozin on cardiac function in diabetic rats. Methods: Diabetes was induced in male Sprague-Dawley rats by streptozotocin injection. Rats were randomly assigned to receive dapagliflozin (1 mg/kg/day) or vehicle for 8 weeks. Cardiac function was assessed by echocardiography. Myocardial fibrosis and oxidative stress markers were measured. Results: Dapagliflozin treatment significantly improved left ventricular ejection fraction and reduced myocardial fibrosis. Oxidative stress markers were decreased in the dapagliflozin group. Conclusions: Dapagliflozin improves cardiac function in diabetic rats through reduction of myocardial fibrosis and oxidative stress.",
    "authors": "Lee TM, Chang NC, Lin SZ",
    "journal": "Cardiovascular Diabetology",
    "publicationYear": 2019,
    "doi": "10.1186/s12933-019-0876-5",
    "expectedDecision": "exclude",
    "rationale": "动物实验（大鼠），不是人类研究，应排除"
  },
  {
    "id": "test-005",
    "title": "Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy",
    "abstract": "Background: Type 2 diabetes is the leading cause of kidney failure worldwide. The effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, on renal outcomes are uncertain. Methods: In this double-blind trial, we randomly assigned 4401 participants with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin at a dose of 100 mg daily or placebo. All participants had an estimated glomerular filtration rate of 30 to <90 ml per minute per 1.73 m² and albuminuria. The primary outcome was a composite of end-stage kidney disease, doubling of serum creatinine level, or death from renal or cardiovascular causes. Results: The trial was stopped early after a median follow-up of 2.6 years. The primary outcome occurred in 43.2 events per 1000 patient-years in the canagliflozin group and 61.2 events per 1000 patient-years in the placebo group (hazard ratio, 0.70; 95% CI, 0.59-0.82; P=0.00001). Conclusions: In participants with type 2 diabetes and kidney disease, canagliflozin reduced the risk of kidney failure and cardiovascular events.",
    "authors": "Perkovic V, Jardine MJ, Neal B, et al.",
    "journal": "New England Journal of Medicine",
    "publicationYear": 2019,
    "doi": "10.1056/NEJMoa1811744",
    "expectedDecision": "include",
    "rationale": "RCT研究，SGLT2抑制剂，有安慰剂对照，虽然主要结局是肾脏结局，但也评估了心血管事件，可纳入"
  },
  {
    "id": "test-006",
    "title": "Real-World Experience with SGLT2 Inhibitors: A Retrospective Cohort Study",
    "abstract": "Objective: To evaluate the real-world effectiveness and safety of SGLT2 inhibitors in patients with type 2 diabetes. Methods: We conducted a retrospective cohort study using electronic health records from a large healthcare system. We identified 12,543 adults with type 2 diabetes who initiated SGLT2 inhibitor therapy between 2014 and 2020. Primary outcomes were changes in HbA1c, body weight, and blood pressure at 6 and 12 months. Safety outcomes included genital infections, urinary tract infections, and diabetic ketoacidosis. Results: Mean HbA1c decreased by 0.8% at 6 months and 0.7% at 12 months. Body weight decreased by 2.3 kg at 6 months. The rate of genital infections was 7.2% and urinary tract infections was 8.5%. Diabetic ketoacidosis occurred in 0.3% of patients. Conclusions: In real-world practice, SGLT2 inhibitors demonstrated effectiveness in glycemic control and weight reduction with acceptable safety profile.",
    "authors": "Patorno E, Pawar A, Franklin JM, et al.",
    "journal": "Diabetes, Obesity and Metabolism",
    "publicationYear": 2020,
    "doi": "10.1111/dom.14000",
    "expectedDecision": "exclude",
    "rationale": "回顾性队列研究，不是RCT，且无对照组，不符合研究设计要求"
  },
  {
    "id": "test-007",
    "title": "Pharmacokinetics and Pharmacodynamics of Empagliflozin in Healthy Volunteers",
    "abstract": "Background: Understanding the pharmacokinetic and pharmacodynamic properties of empagliflozin is essential for optimal clinical use. Methods: In this Phase 1 study, we evaluated the pharmacokinetics and pharmacodynamics of empagliflozin in 48 healthy male volunteers. Participants received single oral doses of empagliflozin (1, 5, 10, 25, 50, or 100 mg) in a randomized, placebo-controlled, double-blind manner. Blood and urine samples were collected for pharmacokinetic analysis. Urinary glucose excretion was measured as a pharmacodynamic endpoint. Results: Empagliflozin was rapidly absorbed with peak plasma concentrations at 1.5 hours post-dose. The elimination half-life was approximately 12 hours. Urinary glucose excretion increased dose-dependently. Empagliflozin was generally well tolerated. Conclusions: Empagliflozin exhibits dose-proportional pharmacokinetics and induces sustained urinary glucose excretion in healthy volunteers.",
    "authors": "Heise T, Seewaldt-Becker E, Macha S, et al.",
    "journal": "Clinical Pharmacokinetics",
    "publicationYear": 2013,
    "doi": "10.1007/s40262-013-0050-3",
    "expectedDecision": "exclude",
    "rationale": "Phase 1药代动力学研究，受试者为健康志愿者而非糖尿病患者，应排除"
  },
  {
    "id": "test-008",
    "title": "Comparative Effectiveness of SGLT2 Inhibitors versus DPP-4 Inhibitors in Elderly Patients with Type 2 Diabetes",
    "abstract": "Background: The comparative effectiveness of SGLT2 inhibitors and DPP-4 inhibitors in elderly patients remains unclear. Methods: We conducted a nationwide cohort study using claims data from Medicare beneficiaries aged ≥65 years with type 2 diabetes. We compared patients initiating SGLT2 inhibitors (n=42,371) with those initiating DPP-4 inhibitors (n=126,806) between 2013 and 2017. Primary outcomes were hospitalization for heart failure and all-cause mortality. Secondary outcomes included major adverse cardiovascular events and acute kidney injury. Results: During a median follow-up of 1.2 years, SGLT2 inhibitors were associated with lower rates of hospitalization for heart failure (HR 0.70, 95% CI 0.63-0.77) and all-cause mortality (HR 0.59, 95% CI 0.53-0.66) compared with DPP-4 inhibitors. The risk of acute kidney injury was also lower with SGLT2 inhibitors. Conclusions: In elderly patients with type 2 diabetes, SGLT2 inhibitors were associated with better cardiovascular and renal outcomes compared with DPP-4 inhibitors.",
    "authors": "Patorno E, Goldfine AB, Schneeweiss S, et al.",
    "journal": "The Lancet Diabetes & Endocrinology",
    "publicationYear": 2018,
    "doi": "10.1016/S2213-8587(18)30190-1",
    "expectedDecision": "exclude",
    "rationale": "观察性队列研究，虽然有比较组（DPP-4抑制剂）但不是RCT，且对照组不是安慰剂或常规疗法"
  },
  {
    "id": "test-009",
    "title": "Severe Diabetic Ketoacidosis Associated with SGLT2 Inhibitor Use: A Case Report",
    "abstract": "Introduction: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been associated with rare cases of diabetic ketoacidosis. We report a case of severe euglycemic diabetic ketoacidosis in a patient treated with dapagliflozin. Case Presentation: A 52-year-old man with type 2 diabetes on dapagliflozin 10 mg daily presented to the emergency department with nausea, vomiting, and abdominal pain. Despite a blood glucose of 180 mg/dL, arterial blood gas showed severe metabolic acidosis (pH 7.08, HCO3 8 mEq/L) with elevated beta-hydroxybutyrate. The patient was diagnosed with euglycemic diabetic ketoacidosis. Dapagliflozin was discontinued, and the patient was treated with intravenous insulin and fluids. He recovered completely within 48 hours. Discussion: Clinicians should be aware of the risk of euglycemic diabetic ketoacidosis with SGLT2 inhibitors, particularly in patients with concurrent illness or reduced oral intake. Conclusion: This case highlights the importance of recognizing atypical presentations of diabetic ketoacidosis in patients taking SGLT2 inhibitors.",
    "authors": "Brown JB, Pedula K, Barzilay J, et al.",
    "journal": "Diabetes Care",
    "publicationYear": 2017,
    "doi": "10.2337/dc16-2460",
    "expectedDecision": "exclude",
    "rationale": "病例报告，不是RCT，应排除"
  },
  {
    "id": "test-010",
    "title": "Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment",
    "abstract": "Background: The effects of sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, on cardiovascular and renal outcomes in patients with type 2 diabetes and moderate renal impairment have not been fully elucidated. Methods: In this randomized, double-blind, placebo-controlled trial, we enrolled 10,584 patients with type 2 diabetes, cardiovascular disease, and an estimated glomerular filtration rate of 25 to 60 ml per minute per 1.73 m². Patients were randomly assigned to receive sotagliflozin 200 mg or placebo once daily. The primary outcome was the total number of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure. Results: After a median follow-up of 16 months, the primary outcome occurred with lower frequency in the sotagliflozin group than in the placebo group (rate ratio, 0.74; 95% CI, 0.63-0.88; P<0.001). The benefits were consistent across subgroups. The incidence of adverse events was similar in the two groups. Conclusions: In patients with type 2 diabetes, moderate renal impairment, and cardiovascular disease, sotagliflozin reduced the composite of cardiovascular deaths and hospitalizations for heart failure.",
    "authors": "Bhatt DL, Szarek M, Steg PG, et al.",
    "journal": "New England Journal of Medicine",
    "publicationYear": 2021,
    "doi": "10.1056/NEJMoa2030186",
    "expectedDecision": "uncertain",
    "rationale": "RCT研究，但sotagliflozin是双重SGLT1/SGLT2抑制剂，与单纯SGLT2抑制剂有所不同，可能需要进一步判断是否符合干预措施标准。且主要结局为心血管死亡和心衰住院，符合PICO标准。倾向于uncertain或include"
  }
]



