A Safety Comparison of Metformin vs Sulfonylurea Initiation in Patients With Type 2 Diabetes and Chronic Kidney Disease: A Retrospective Cohort Study

Whitlock, Reid; Hougen, Ingrid; Komenda, Paul; Rigatto, Claudio; Clemens, Kristin K.; Tangri, Navdeep

doi:10.1016/j.mayocp.2019.07.017

Cited by 29 publications

(36 citation statements)

References 50 publications

(47 reference statements)

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“…initial search found 7,439 potentially feasible articles, and after title and abstract screening, 51 articles were retrieved for full-text assessment. Finally, 13 studies were included, including 3 p-h/sa of RCTs (16,24,25), 9 cohort studies (CSs) (15,18,(26)(27)(28)(29)(30)(31)(32), and 1 nested case-control study (17) (Figure 1). Of the 13 studies, sample sizes varied from 1016 to 175,296, mean age of patients was 55.5 to 69.6 years, female proportion was 1.57% to 59.31%, duration of DM was 5.9 to 14.6 years, and follow-up duration was 1 to 7.3 years.…”

Section: Study Selection Characteristics and Quality Assessmentmentioning

confidence: 99%

“…Except for the multinational origins in 3 studies (16,24,25), other origins included Europe and America in 7 articles (17, 26-29, 31, 32), and Asia in 3 articles (15,18,30). The control was set as sulfonylurea in 3 studies (29,31,32), lifestyle modification in 1 article (30), thiazolidinedione in 1 study (26), glyburid and insulin in 1 study (17), and metformin non-users in the rest studies. CKD definitions varied and were eGFR-based in 10 studies and serum creatinine-based in the other three studies (15,26,29).…”

Section: Study Selection Characteristics and Quality Assessmentmentioning

confidence: 99%

“…All studies adjusted for several baseline participant discrepancies between metformin use and non-use; 7 utilized propensity scores. All studies presented data with all-cause mortality, and four studies reported data of cardiovascular events (25,28,30,32). Table 1 summarized the major information of the 13 studies.…”

Section: Study Selection Characteristics and Quality Assessmentmentioning

confidence: 99%

“…Six studies reported the effect of metformin use versus any other measure on all-cause mortality in patients with T2DM and mild/ moderate CKD (18,25,28,(30)(31)(32). The pooled RR was 0.71 (95% CI, 0.61 to 0.84; P<0.001) in a random-effects model, with severe heterogeneity (I 2 = 79.0%; P<0.001; Figure 2).…”

Section: Effect Of Metformin On All-cause Mortality In Patients With mentioning

confidence: 99%

“…The 4 relevant studies (25,28,30,32) on G1-3 CKD patients (eGFR≥30 ml/min/1.73m 2 ) reported that metformin use induced a significant 24% decline (pooled RR, 0.76; 95% CI, 0.60-0.97; P=0.024) in susceptibility to cardiovascular events in a randomeffects model with considerable heterogeneity (I 2 = 87.0%; P<0.001). But no significant effect of metformin use on advanced CKD was found (pooled RR: 0.94; 95%CI: 0.68, 1.30), without heterogeneity ( Figure 4).…”

Section: Effect Of Metformin Treatment Versus Non-metformin Treatmentmentioning

confidence: 99%

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Metformin Use and Risk of All-Cause Mortality and Cardiovascular Events in Patients With Chronic Kidney Disease—A Systematic Review and Meta-Analysis

Lei

et al. 2020

Front. Endocrinol.

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Background: To evaluate whether metformin use assuredly alters overall all-cause death in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Methods: Pubmed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials were systematically searched from inception to Feb. 29, 2020 with no language restriction. All related articles comparing all-cause death of T2DM and CKD patients after metformin use (monotherapy or combination) versus non-metformin treatment were identified. Pooled risk ratios (RR) and 95% confidence intervals (CI) were computed using random-effects models regardless of the heterogeneity quantified by Cochrane c 2 and I 2 statistics. Results: Totally 13 studies (9 cohort studies [CSs], 3 subanalyses or post-hoc analyses of randomized controlled trials [RCTs], and 1 nested case-control article) involving 303,540 patients were included. Metformin-based treatments relative to any other measure displayed significantly lower risks of all-cause mortality (Pooled RRs 0.71, 95%CI 0.61 to 0.84; I 2 = 79.0%) and cardiovascular events (Pooled RRs 0.76, 95%CI 0.60 to 0.97; I 2 = 87.0%) in CKD patients at stage G1-3, with substantial heterogeneity. Metformin use was not significantly related with these end points in advanced CKD patients. Conclusions: Metformin use is connected with significantly less risks of all-cause mortality and cardiovascular events in patients with T2DM and mild/moderate CKD. However, RCTs with large sample sizes are warranted in the future to assess whether these key benefits extend to later stages of CKD by dose adjustment.

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Section: Study Selection Characteristics and Quality Assessmentmentioning

confidence: 99%

Section: Study Selection Characteristics and Quality Assessmentmentioning

confidence: 99%

Section: Study Selection Characteristics and Quality Assessmentmentioning

confidence: 99%

Section: Effect Of Metformin On All-cause Mortality In Patients With mentioning

confidence: 99%

Section: Effect Of Metformin Treatment Versus Non-metformin Treatmentmentioning

confidence: 99%

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Metformin Use and Risk of All-Cause Mortality and Cardiovascular Events in Patients With Chronic Kidney Disease—A Systematic Review and Meta-Analysis

Lei

et al. 2020

Front. Endocrinol.

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Metformin versus sulphonylureas for new onset atrial fibrillation and stroke in type 2 diabetes mellitus: a population-based study

et al. 2022

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Background To compare the rates of incident atrial brillation (AF), stroke, cardiovascular mortality, and all-cause mortality between metformin and sulphonylurea users in type 2 diabetes mellitus. Methods This was a retrospective population-based cohort study of type 2 diabetes mellitus patients receiving either sulphonylurea or metformin monotherapy between January 1 st , 2000 and December 31 st , 2019. The primary outcome was new-onset AF or stroke.Secondary outcomes were cardiovascular, non-cardiovascular and all-cause mortality. Propensity score matching (1:2 ratio) between sulphonylurea and metformin users was performed, based on demographics, CHA-DS-VASc score, Charlson comorbidity index, past comorbidities, and medication use. Cox regression was used to identify signi cant risk factors. Competing risk analysis was conducted using cause-speci c and subdistribution hazard models. Sensitivity analysis using propensity score strati cation, high dimensional propensity score and inverse probability of treatment weighting were conducted.Results A total of 36228 sulphonylurea users and 72456 metformin users were included in the propensity score-matched cohort. Multivariable Cox regression showed that sulphonylurea users had higher risks of incident AF (hazard ratio [HR]: 2.89, 95% con dence interval [CI]: 2.75-2.77; P<0.0001), stroke (HR: 3.23, 95% CI: 3.01-3.45; P<0.0001), cardiovascular mortality (HR: 3.60, 95% CI: 2.62-4.81; P<0.0001), and all-cause mortality (HR: 4.35, 95% CI: 3.16-4.75; P<0.0001) compared to metformin users. Similarly signi cant results were observed using cause-speci c and subdistribution hazard models. Sensitvity analysis using other propensity score techniques also yielded higher risks in sulphonylurea users. Conclusions Sulphonylurea use was associated with higher risks of incident AF, stroke, cardiovascular mortality and all-cause mortality compared to metformin. BackgroundType 2 diabetes mellitus (T2DM) is one of the most prevalent chronic disorders around the world which leads to signi cant morbidity and mortality [1]. It is predicted that by 2040, T2DM would have a global prevalence of 600 million people [2, 3]. T2DM is associated with multisystem complications including atrial brillation (AF) and stroke [4]. The manifestations of metabolic syndrome transform the epicardial adipose tissue to cause brosis, resulting in atrial remodelling [5]. Furthermore, the sympathetic activity is also increased in T2DM patients [6]. Hence, it has been reported that T2DM patients has a 40% increase in AF risk [7, 8]. Besides, The T2DM insulin resistance state leads to endothelium-dependent vasodilation impairment [9]. The T2DM induced hyperglycemia also damages the vessels by reducing the endothelium-derived NO via inhibiting the phosphatidylinositol 3 kinase pathway. This leads to increase in ammation and formation of foam cells [10]. As such, the T2DM patients also have an increased risk of stroke incidences due to the direct or indirect diabetic-induced changes in the cerebral vessels.Glycaemic co...

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Type 2 diabetes and CKD: safety of metformin vs sulfonylureas

2020

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A Safety Comparison of Metformin vs Sulfonylurea Initiation in Patients With Type 2 Diabetes and Chronic Kidney Disease: A Retrospective Cohort Study

Cited by 29 publications

References 50 publications

Metformin Use and Risk of All-Cause Mortality and Cardiovascular Events in Patients With Chronic Kidney Disease—A Systematic Review and Meta-Analysis

Metformin Use and Risk of All-Cause Mortality and Cardiovascular Events in Patients With Chronic Kidney Disease—A Systematic Review and Meta-Analysis

Metformin versus sulphonylureas for new onset atrial fibrillation and stroke in type 2 diabetes mellitus: a population-based study

Type 2 diabetes and CKD: safety of metformin vs sulfonylureas

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