scholarly journals SGLT2 inhibitors and the risk of diabetic ketoacidosis among adults with Type 2 Diabetes: A systematic review and meta-analysis

2021 ◽  
Author(s):  
Michael Colacci ◽  
John Fralick ◽  
Ayodele Odutayo ◽  
Michael Fralick
Keyword(s):  
Diabetic Ketoacidosis ◽  
Observational Studies ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Controlled Trials ◽  
Absolute Rate ◽  
Randomized Controlled

Importance: The risk of diabetic ketoacidosis (DKA) with sodium-glucose cotransporter-2 (SGLT2) inhibitors is unclear. Objective: To examine the risk of DKA with SGLT2 inhibitors in both observational studies and large clinical trials. Data Sources: Searches of PubMed, EMBASE and CENTRAL (inception to 15 April 2019) without language restrictions; conference proceedings; and reference lists. Study Selection: Randomized controlled trials and observational studies that quantified the rate of diabetic ketoacidosis with an SGLT2 inhibitor in comparison to another diabetes medication or placebo. Data Extraction and Synthesis: Two independent investigators abstracted study data and assessed the quality of evidence. Data were pooled using random effects models with the Hartung-Knapp-Sidik-Jonkman method. Main Outcome and Measures: Absolute event rates and hazard ratios for diabetic ketoacidosis were extracted from each study. Results: Seven randomized trials encompassing 42,375 participants and five cohort studies encompassing 318,636 participants were selected. Among the 7 randomized controlled trials, the absolute rate of DKA among patients randomized to an SGLT2 inhibitor ranged from 0.6 to 2.2 events per 1000 person years. Four randomized trials were included in the meta-analysis, and compared to placebo or comparator medication, SGLT2 inhibitors had a 2.4-fold higher risk of DKA (Relative Risk [RR] = 2.46 [95% CI, 1.16-5.21]; I2 = 0%; P = 0.54). Among the 5 observational studies, the absolute rate of DKA associated with SGLT2 inhibitor use ranged from 0.6 to 4.9 per 1000 person years and a 1.7-fold higher rate of DKA compared to another diabetes medication (RR = 1.74 [95% CI, 1.01-2.93]; I2 = 45%; P = 0.12). Conclusions and Relevance: In adults with type 2 diabetes, SGLT2 inhibitors increase the risk of DKA in both observational studies and large randomized clinical trials. Registration: CRD42019146855 Funding Source: None

scholarly journals Systematic Review and Meta-Analysis of Randomized Controlled Trials on the Effect of SGLT2 Inhibitor on Blood Leptin and Adiponectin Level in Patients with Type 2 Diabetes

2019 ◽  
Vol 51 (08) ◽  
pp. 487-494 ◽  
Author(s):  
Peili Wu ◽  
Weiheng Wen ◽  
Jitong Li ◽  
Jie Xu ◽  
Min Zhao ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Sglt2 Inhibitor ◽  
Placebo Treatment ◽  
Sglt2 Inhibitors ◽  
Controlled Trials ◽  
Beneficial Effects ◽  
Randomized Controlled

AbstractSodium glucose cotransporter 2 (SGLT2) inhibitors are a new kind of hypoglycemic drugs that improve glucose homeostasis by inhibiting renal glucose reabsorption. Recent studies have shown that SGLT2 inhibitors can also mediate body metabolism through regulation of adipokines level, but the effects of SGLT2 inhibitors on the concentration of adipokines (leptin and adiponectin) remains controversial. This meta-analysis was set out to evaluate the changes in circulating leptin and adiponectin levels in patients with type 2 diabetes mellitus (T2DM) receiving SGLT2 inhibitors therapy. Ten randomized controlled trials (RCTs), that evaluated the effects of SGLT2 inhibitors on blood leptin and adiponectin levels in patients with type 2 diabetes, were identified by performing a systematic search of Pubmed, Embase, Cochrane, and Web of science databases through July 2018. Data were calculated using a random-effects model and presented as standardized mean difference (SMD) and 95% confidence interval (CI). Compared with placebo, treatment with SGLT2 inhibitors contributed to a decreased circulating leptin levels (SMD −0.29, 95% CI −0.56, −0.03) and an increased circulating adiponectin levels (SMD 0.30, 95% CI 0.22, 0.38). SGLT2 inhibitor treatment was associated with decreased circulating leptin levels and increased circulating adiponectin levels, which might contribute to the beneficial effects of SGLT2 inhibitors on metabolic homeostasis.

scholarly journals Sodium-glucose co-transporter 2 inhibitors (SGLT2i); as a preventive factor of kidney failure in patients with type 2 diabetes; a meta-analysis of randomized controlled trials

2021 ◽  
Vol 10 (4) ◽  
pp. e35-e35
Author(s):  
Dorsa Jahangiri ◽  
Udit Narayan Padhi ◽  
Henu Kumar Verma ◽  
Bhaskar VKS Lakkakula ◽  
Rohollah Valizadeh ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Meta Analysis ◽  
Sglt2 Inhibitors ◽  
Renal Outcome ◽  
Diabetic Patients ◽  
Controlled Trials ◽  
Randomized Controlled

Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new class of anti-diabetic drugs. SGLT2 inhibitors lower blood glucose levels by decreasing glucose reabsorption in the proximal renal tubule, resulting in increased urinary glucose and sodium excretion. Objective: This study was conducted to investigate the effects of SGLT2i on individual renal outcomes in diabetic patients. Methods: This study was a systematic review and meta-analysis of clinical trials. A comprehensive search of Cochrane Central Register of Controlled Trials was conducted in the Cochrane Library and PubMed, to identify relevant articles focusing on SGLT2i and chronic kidney disease (CKD) in diabetic patients. The most recent article search was conducted on July 12, 2021. Results: Seven randomized controlled trials (RCTs) were included in the meta-analysis. Two trials were comparing dapagliflozin, two comparing empagliflozin, one comparing ertugliflozin, one comparing canagliflozin, and one comparing sotagliflozin. Composite renal outcome and acute kidney injury (AKI) was found in seven and four studies, respectively. Data on end-stage kidney disease (ESKD) and albuminuria or initiation of renal replacement therapy were reported in the two studies. The pooled risk ratio (RR) 95% confidence interval (CI) for the composite renal outcome was 0.54 (0.50–0.59), with 92 % heterogeneity. The pooled RR for AKI was 0.77 (0.66–0.89), with no heterogeneity. A significant lower incidence of albuminuria (RR: 0.69; 95% CI: 0.59–0.81), initiation of renal replacement therapy (RR: 0.71; 95% CI: 0.58–0.87), was observed following the use of SGLT2 inhibitors. Conclusion: Our findings confirm that the SGLT2 inhibitors can reduce the risk of albuminuria, AKI and renal replacement therapy in ESKD patients with T2D (type 2 diabetes). These meta-analyses provide substantial evidence supporting the beneficial effect of SGLT2 inhibitors on reducing CKD events in individuals with T2D.

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