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Importance: Additional treatments are needed for heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 (SGLT2) inhibitors may be an effective treatment for patients with HFrEF, even those without diabetes.Objective: To evaluate the effects of dapagliflozin in patients with HFrEF with and without diabetes.Design, Setting, and Participants: Exploratory analysis of a phase 3 randomized trial conducted at 410 sites in 20 countries. Patients with New York Heart Association classification II to IV with an ejection fraction less than or equal to 40% and elevated plasma N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019.Interventions: Addition of once-daily 10 mg of dapagliflozin or placebo to recommended therapy.Main Outcomes and Measures: The primary outcome was the composite of an episode of worsening heart failure or cardiovascular death. This outcome was analyzed by baseline diabetes status and, in patients without diabetes, by glycated hemoglobin level less than 5.7% vs greater than or equal to 5.7%.Results: Among 4744 patients randomized (mean age, 66 years; 1109 [23%] women; 2605 [55%] without diabetes), 4742 completed the trial. Among participants without diabetes, the primary outcome occurred in 171 of 1298 (13.2%) in the dapagliflozin group and 231 of 1307 (17.7%) in the placebo group (hazard ratio, 0.73 [95% CI, 0.60-0.88]). In patients with diabetes, the primary outcome occurred in 215 of 1075 (20.0%) in the dapagliflozin group and 271 of 1064 (25.5%) in the placebo group (hazard ratio, 0.75 [95% CI, 0.63-0.90]) (P value for interaction = .80). Among patients without diabetes and a glycated hemoglobin level less than 5.7%, the primary outcome occurred in 53 of 438 patients (12.1%) in the dapagliflozin group and 71 of 419 (16.9%) in the placebo group (hazard ratio, 0.67 [95% CI, 0.47-0.96]). In patients with a glycated hemoglobin of at least 5.7%, the primary outcome occurred in 118 of 860 patients (13.7%) in the dapagliflozin group and 160 of 888 (18.0%) in the placebo group (hazard ratio, 0.74 [95% CI, 0.59-0.94]) (P value for interaction = .72). Volume depletion was reported as an adverse event in 7.3% of patients in the dapagliflozin group and 6.1% in the placebo group among patients without diabetes and in 7.8% of patients in the dapagliflozin group and 7.8% in the placebo group among patients with diabetes. A kidney adverse event was reported in 4.8% of patients in the dapagliflozin group and 6.0% in the placebo group among patients without diabetes and in 8.5% of patients in the dapagliflozin group and 8.7% in the placebo group among patients with diabetes.Conclusions and Relevance: In this exploratory analysis of a randomized trial of patients with HFrEF, dapagliflozin compared with placebo, when added to recommended therapy, significantly reduced the risk of worsening heart failure or cardiovascular death independently of diabetes status.Trial Registration: ClinicalTrials.gov Identifier: NCT03036124. [ABSTRACT FROM AUTHOR]

Importance: Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis.Objective: To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function.Evidence Acquisition: In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining to metformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014. We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial.Results: Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73 m2). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100,000 person-years to 10 per 100,000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety of metformin in patients with significantly impaired kidney function. Population-based studies demonstrate that metformin may be prescribed counter to prevailing guidelines suggesting a renal risk in up to 1 in 4 patients with type 2 diabetes mellitus--use which, in most reports, has not been associated with increased rates of lactic acidosis. Observational studies suggest a potential benefit from metformin on macrovascular outcomes, even in patients with prevalent renal contraindications for its use.Conclusions and Relevance: Available evidence supports cautious expansion of metformin use in patients with mild to moderate chronic kidney disease, as defined by estimated glomerular filtration rate, with appropriate dosage reductions and careful follow-up of kidney function. [ABSTRACT FROM AUTHOR]

The article reports on the results of research which was conducted in an effort to determine whether the mortality risk associated with hypoglycemic events is similar in patients who develop hypoglycemia spontaneously and those who develop it as a result of insulin therapy. Researchers used a retrospective cohort study which used data from Health Facts, a database of patients hospitalized across the U.S. They found that while hypoglycemia was associated with increased mortality in patients with acute myocardial infarction, this risk was confined to patients who developed hypoglycemia spontaneously. They also found that iatrogenic hypoglycemia after insulin therapy was not associated with higher mortality risk.

Context: While glucose control is recommended by professional societies for patients with hyperglycemia hospitalized with acute myocardial infarction (AMI), enthusiasm for glucose lowering is tempered, in part, by concerns of inducing hypoglycemia. Yet, whether episodic hypoglycemia that occurs as a result of glucose-lowering therapy is harmful in patients with AMI is unknown.Objective: To determine whether the mortality risk associated with hypoglycemic events is similar in patients who develop hypoglycemia spontaneously and those who develop it as a result of insulin therapy.Design, Setting, and Patients: Retrospective cohort study using data from Health Facts, a contemporary database of patients hospitalized across the United States in 40 hospitals between January 1, 2000, and December 31, 2005. Of all the patients in the database, 7820 patients were hospitalized with AMI and were hyperglycemic on admission (glucose level > or = 140 mg/dL). Patients were stratified based on whether they developed a hypoglycemic event (random glucose level < 60 mg/dL) during subsequent hospitalization. Logistic regression models were used to evaluate the association between hypoglycemia and in-hospital mortality within subgroups of patients who were and were not treated with insulin therapy.Main Outcome Measure: All-cause in-hospital mortality.Results: Among patients treated or not treated with insulin, those with hypoglycemia were older and had more comorbidity. Hypoglycemia was associated with increased mortality in patients not treated with insulin (18.4% [25/136] mortality in patients with hypoglycemia vs 9.2% [425/4639] in those without hypoglycemia; P<.001), but not in those treated with insulin (10.4% [36/346] mortality in patients with hypoglycemia vs 10.2% [276/2699] in those without hypoglycemia; P = .92). After multivariable adjustment, there was a significant interaction between hypoglycemia and insulin therapy (P value for interaction = .01). Hypoglycemia was a predictor of higher mortality in patients who were not treated with insulin (odds ratio, 2.32 [95% confidence interval, 1.31-4.12] vs patients without hypoglycemia), but not in patients treated with insulin (odds ratio, 0.92 [95% confidence interval, 0.58-1.45] vs patients without hypoglycemia).Conclusions: While hypoglycemia was associated with increased mortality in patients with AMI, this risk was confined to patients who developed hypoglycemia spontaneously. In contrast, iatrogenic hypoglycemia after insulin therapy was not associated with higher mortality risk. [ABSTRACT FROM AUTHOR]

The article reports on the results of research which was conducted in an effort to assess whether routine screening for coronary artery disease identifies patients with type 2 diabetes as being at high cardiac risk and whether it effects their cardiac outcomes. Researchers used a randomized controlled trial to evaluate 1,123 subjects with type 2 diabetes. They found that in the population of patients that they studied, the cardiac event rates were low and were not significantly reduced by myocardial perfusion imaging screening for myocardial ischemia over 4.8 years.

Context: According to package inserts, metformin is contraindicated in diabetic patients receiving drug treatment for heart failure therapy, and thiazolidinediones are not recommended in diabetic patients with symptoms of advanced heart failure. Little is known about patterns of use of these antihyperglycemic drugs in diabetic patients with heart failure. Objective: To determine the proportions of patients hospitalized with heart failure and concomitant diabetes treated with metformin or thiazolidinediones. Design: Serial cross-sectional measurements using data from retrospective medical record abstraction. Setting: Nongovernmental acute care hospitals in the United States. Patients: Two nationally representative samples of Medicare beneficiaries hospitalized with the primary diagnosis of heart failure and concomitant diabetes between April 1998 and March 1999 and between July 2000 and June 2001. Main Outcome Measures: The prescription of either metformin or a thiazolidinedione at hospital discharge. Results: In the 1998-1999 sample (n = 12 505), 7.1% of patients were discharged with a prescription for metformin, 7.2% with a prescription for a thiazolidinedione, and 13.5% with a prescription for either drug. In the 2000-2001 sample (n = 13 158), metformin use increased to 11.2%, thiazolidinedione use to 16.1%, and use of either drug to 24.4% (P<.001 for all comparisons). Similar increases were seen among patients of all age groups, all races, and both sexes. Conclusions: The use of metformin and thiazolidinediones is common and has increased rapidly in Medicare beneficiaries with diabetes and heart failure in direct contrast with explicit warnings against this practice by the Food and Drug Administration. Further studies to establish the safety and effectiveness of this practice are needed to ensure optimal care of patients with diabetes and heart failure. [ABSTRACT FROM AUTHOR]

Presents letters to the editor as of April 3, 2002. Drug therapy for patients with type-2 diabetes; Treatment decisions for type-2 diabetes; Costs of making practice more cost-effective; Poliomyelitis and Parkinson Disease.

Presents a study to systematically review available data from the literature regarding the efficacy of oral antidiabetic agents, both as monotherapy and in combination. Context; Objective; Data sources; Study selection and data extraction; Data synthesis; Conclusion that the available oral antidiabetic agents are equally effective at lowering glucose concentrations.