Comparative Safety of Sulfonylurea and Metformin Monotherapy on the Risk of Heart Failure: A Cohort Study

Roumie, Christianne L.; Min, Jea Young; McGowan, Lucy D’Agostino; Presley, Caroline A.; Grijalva, Carlos G.; Hackstadt, Amber J.; Hung, Adriana M.; Greevy, Robert A.; Elasy, Tom A.; Griffin, Marie R.

doi:10.1161/jaha.116.005379

Cited by 81 publications

(68 citation statements)

References 45 publications

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“…More recently, Hung et al studied 95 577 US veterans with eGFR above or equal to 60 mL/min/1.73m 2 and found that, compared with initial treatment with metformin, sulfonylurea use was associated with a 20% increase in the risk of both combined ESRD or with a 25% sustained decrease in eGFR and in the combined endpoint of ESRD, sustained decrease in eGFR or death . This group subsequently found that, among individuals with serum creatinine below 1.5 mg/dL in men or 1.4 mg/dL in women, metformin use was associated with reduced risk of both heart failure and cardiovascular death compared to sulfonylurea use …”

Section: Discussionmentioning

confidence: 99%

Metformin use and cardiovascular events in patients with type 2 diabetes and chronic kidney disease

Charytan

Solomon

Ivanovich

et al. 2019

Diabetes Obesity Metabolism

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Aims Metformin could have benefits on cardiovascular disease and kidney disease progression but is often withheld from individuals with diabetes and chronic kidney disease (CKD) because of a concern that it may increase the risk of lactic acidosis. Materials and methods All‐cause mortality, cardiovascular death, cardiovascular events (death, hospitalization for heart failure, myocardial infarction, stroke or myocardial ischemia), end stage renal disease (ESRD) and the kidney disease composite (ESRD or death) were compared in metformin users and non‐users with diabetes and CKD enrolled in the Trial to Reduce Cardiovascular Events with Aranesp (darbepoeitin‐alfa) Therapy (TREAT) (NCT00093015). Outcomes were compared after propensity matching of users and non‐users and in multivariable proportional hazards models. Results There were 591 individuals who used metformin at baseline and 3447 non‐users. Among propensity‐matched users, the crude incidence rate for mortality, cardiovascular mortality, cardiovascular events and the combined endpoint was lower in metformin users than in non‐users, but ESRD was marginally higher (4.0% vs 3.6%). Metformin use was independently associated with a reduced risk of all‐cause mortality (HR, 0.49; 95% CI, 0.36‐0.69), cardiovascular death (HR, 0.49; 95% CI, 0.32‐0.74), the cardiovascular composite (HR, 0.67, 95% CI, 0.51‐0.88) and the kidney disease composite (HR, 0.77; 95% CI, 0.61‐0.98). Associations with ESRD (HR, 1.01; 95% CI, 0.65‐1.55) were not significant. Results were qualitatively similar in adjusted analyses of the full population. Two cases of lactic acidosis were observed. Conclusions Metformin may be safer for use in CKD than previously considered and may lower the risk of death and cardiovascular events in individuals with stage 3 CKD.

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Section: Discussionmentioning

confidence: 99%

Metformin use and cardiovascular events in patients with type 2 diabetes and chronic kidney disease

Charytan

Solomon

Ivanovich

et al. 2019

Diabetes Obesity Metabolism

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“…Strategies for the identification of patients with T2DM from a single hospital or within a single network‐based EHR system have been reported and applied extensively, although prior studies used different inclusion and exclusion criteria to identify patients with T2DM . Of those that applied specific algorithms requiring multiple sources of evidence to identify patients with T2DM (ie, >1 of either a coded diagnosis, prescribed antidiabetic medications or elevated laboratory values; in addition to evidence of baseline enrollment and health care utilization), the study populations ranged in size from 10 000 to 500 000 patients . Distinct from our study, several of these prior studies centered only on a single health care system or used coded diagnoses, antidiabetic medication use, and laboratory values to identify patients with T2DM from de‐identified, commercially available databases, which could not be validated against patients' EHR information .…”

Section: Discussionmentioning

confidence: 99%

“…Large well‐designed observational studies can help identify the benefits and harms of specific treatments among patients with T2DM, particularly among those who may be underrepresented in clinical trials (ie, the elderly and those with certain comorbidities such as heart and renal disease) . The identification of patients with T2DM from EHR and administrative databases has been conducted extensively in the prior literature …”

Section: Introductionmentioning

confidence: 99%

“…Most previous studies have identified and studied patients with T2DM using EHR and administrative databases within well‐defined but single data systems. However, less is known about the implementation of those strategies across diverse systems and at a large scale . Therefore, T2DM represented an optimal condition for us to construct, characterize and validate a cohort of patients with T2DM across four diverse PCORnet sites to determine the utility of using these integrated data to conduct epidemiological and comparative effectiveness research.…”

Section: Introductionmentioning

confidence: 99%

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Performance of a computable phenotype for identification of patients with diabetes within PCORnet: The Patient‐Centered Clinical Research Network

Wiese

Roumie

Buse

et al. 2019

Pharmacoepidemiology and Drug

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Purpose PCORnet, the National Patient‐Centered Clinical Research Network, represents an innovative system for the conduct of observational and pragmatic studies. We describe the identification and validation of a retrospective cohort of patients with type 2 diabetes (T2DM) from four PCORnet sites. Methods We adapted existing computable phenotypes (CP) for the identification of patients with T2DM and evaluated their performance across four PCORnet sites (2012‐2016). Patients entered the cohort on the earliest date they met one of three CP categories: (CP1) coded T2DM diagnosis (ICD‐9/ICD‐10) and an antidiabetic prescription, (CP2) diagnosis and glycosylated hemoglobin (HbA1c) ≥6.5%, or (CP3) an antidiabetic prescription and HbA1c ≥6.5%. We required evidence of health care utilization in each of the 2 prior years for each patient, as we also developed an incident T2DM CP to identify the subset of patients without documentation of T2DM in the 365 days before t0. Among a systematic sample of patients, we calculated the positive predictive value (PPV) for the T2DM CP and incident‐T2DM CP using electronic health record (EHR) review as reference. Results The CP identified 50 657 patients with T2DM. The PPV of patients randomly selected for validation was 96.2% (n = 1572; CI:95.1‐97.0) and was consistently high across sites. The PPV for the incident‐T2DM CP was 5.8% (CI:4.5‐7.5). Conclusions The T2DM CP accurately and efficiently identified patients with T2DM across multiple sites that participate in PCORnet, although the incident T2DM CP requires further study. PCORnet is a valuable data source for future epidemiological and comparative effectiveness research among patients with T2DM.

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“…Dipeptidyl peptidase‐4 inhibitors also act to enhance the actions of cyclic AMP in the heart, and both saxagliptin and alogliptin have regulatory labels that indicate an increased risk of new‐onset heart failure in patients with type 2 diabetes . The use of sulphonylureas has not only been associated with an increase in the risk of myocardial infarction and stroke, but these drugs have been associated with worsening heart failure …”

Section: Potential Cardiovascular Risks Of Antidiabetic Drugsmentioning

confidence: 99%

Have we really demonstrated the cardiovascular safety of anti‐hyperglycaemic drugs? Rethinking the concepts of macrovascular and microvascular disease in type 2 diabetes

Packer

2018

Diabetes Obesity Metabolism

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A primary goal of the treatment of type 2 mellitus is the prevention of morbidity and mortality associated with cardiovascular disease; however, anti-hyperglycaemic drugs have the capacity to cause deleterious effects on the circulation, a risk that is not adequately reflected by the endpoints selected for emphasis in large-scale clinical trials that are designed to evaluate cardiovascular safety. The primary endpoint of the large-scale studies mandated by regulatory authorities focuses only on 3 to 4 events that depict only a limited view of the circulatory system. One of the most serious adverse effects of many glucose-lowering drugs is new-onset or worsening heart failure. Most antidiabetic drugs can aggravate heart failure because they exert anti-natriuretic actions, and possibly, adverse effects on the myocardium. In addition, certain anti-hyperglycaemic agents may worsen peripheral vascular disease and trigger cardiac arrhythmias that may lead to sudden death. Initiation of treatment with antidiabetic medications may also cause deterioration of the function of the kidneys, retina and peripheral nerves, which are typically regarded as reflecting microvascular disease. The current confusion about the cardiovascular effects of glucose-lowering drugs may be exacerbated by conceptual uncertainties about the classification of large and small vessel disease in determining the clinical course of diabetes. Physicians should not be falsely reassured by claims that a new treatment appears to have passed a narrowly defined regulatory test. The management of people with diabetes often carries with it the risk of important cardiovascular consequences, even for drugs that do not overtly increase the risk of myocardial infarction or stroke.

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Comparative Safety of Sulfonylurea and Metformin Monotherapy on the Risk of Heart Failure: A Cohort Study

Cited by 81 publications

References 45 publications

Metformin use and cardiovascular events in patients with type 2 diabetes and chronic kidney disease

Metformin use and cardiovascular events in patients with type 2 diabetes and chronic kidney disease

Performance of a computable phenotype for identification of patients with diabetes within PCORnet: The Patient‐Centered Clinical Research Network

Have we really demonstrated the cardiovascular safety of anti‐hyperglycaemic drugs? Rethinking the concepts of macrovascular and microvascular disease in type 2 diabetes

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