2363-PUB: The Efficacy of Low vs. High FDA-Approved SGLT2 Inhibitor Dose Compared with DPP-4 Inhibitors: A Meta-analysis

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 2363-PUB ◽  
Author(s):  
JARROD UHRIG ◽  
BASEM M. MISHRIKY ◽  
STEPHANIE O. PAGE ◽  
KERRY SEWELL ◽  
JAMES R. POWELL ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Sglt2 Inhibitor ◽  
Inhibitor Dose

scholarly journals Combination Therapy with an SGLT2 Inhibitor as Initial Treatment for Type 2 Diabetes: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 8 (1) ◽  
pp. 45 ◽  
Author(s):  
Tamara Y. Milder ◽  
Sophie L. Stocker ◽  
Christina Abdel Shaheed ◽  
Lucy McGrath-Cadell ◽  
Dorit Samocha-Bonet ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Combination Therapy ◽  
Low Dose ◽  
Meta Analysis ◽  
Sglt2 Inhibitor ◽  
Cochrane Library ◽  
High Dose ◽  
Dose Combination ◽  
Inhibitor Combination

Background: Guidelines differ with regard to indications for initial combination pharmacotherapy for type 2 diabetes. Aims: To compare the efficacy and safety of (i) sodium-glucose cotransporter 2 (SGLT2) inhibitor combination therapy in treatment-naïve type 2 diabetes adults; (ii) initial high and low dose SGLT2 inhibitor combination therapy. Methods: PubMed, Embase and Cochrane Library were searched for randomised controlled trials (RCTs) of initial SGLT2 combination therapy. Mean difference (MD) for changes from baseline (HbA1c, weight, blood pressure) after 24–26 weeks of treatment and relative risks (RR, safety) were calculated using a random-effects model. Risk of bias and quality of evidence was assessed. Results: In 4 RCTs (n = 3749) there was moderate quality evidence that SGLT2 inhibitor/metformin combination therapy resulted in a greater reduction in HbA1c (MD (95% CI); −0.55% (−0.67, −0.43)) and weight (−2.00 kg (−2.34, −1.66)) compared with metformin monotherapy, and a greater reduction in HbA1c (−0.59% (−0.72, −0.46)) and weight (−0.57 kg (−0.89, −0.25)) compared with SGLT2 inhibitor monotherapy. The high dose SGLT2 inhibitor/metformin combination resulted in a similar HbA1c but greater weight reduction; −0.47 kg (−0.88, −0.06) than the low dose combination therapy. The RR of genital infection with combination therapy was 2.22 (95% CI 1.33, 3.72) and 0.69 (95% CI 0.50, 0.96) compared with metformin and SGLT2 inhibitor monotherapy, respectively. The RR of diarrhoea was 2.23 (95% CI 1.46, 3.40) with combination therapy compared with SGLT2 inhibitor monotherapy. Conclusions: Initial SGLT2 inhibitor/metformin combination therapy has glycaemic and weight benefits compared with either agent alone and appears relatively safe. High dose SGLT2 inhibitor/metformin combination therapy appears to have modest weight, but no glycaemic benefits compared with the low dose combination therapy.

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 The safety and efficacy of SDLT-2 (Sodium-glucose co-transporter 2) inhibitor versus placebo in the treatment of heart failure in patients with or without T2DM (Type 2 diabetes mellitus): A Systemic Review and Meta-analysis.

2020 ◽  
Author(s):  
Qian Zhang ◽  
Xiaofei Wang ◽  
Peipei Ge ◽  
Aizhen Hu ◽  
Xuexun Li
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Sglt2 Inhibitor ◽  
Systemic Review ◽  
Cochrane Library ◽  
Volume Depletion ◽  
Patients With Heart Failure ◽  
Safety Outcomes

Abstract Background Sodium-glucose co-transporter 2 (SGLT2) inhibitor which is a type of drug used for the treatment of diabetes mellitus, has been reported by many trials that it could be beneficial for patients with established heart failure. A meta-analysis on this subject could obtain more reliable estimates of the efficacy and safety outcomes. Methods A systematic review and meta-analysis of randomized, placebo-controlled trials of SGLT2 inhibitor in patients with heart failure was conducted. We searched PubMed, Cochrane Library, and Web of Science for trials published from inception to March, 2018. PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was used to conduct the review. For quality assessment of included studies. The methodological quality of the included trials was assessed using the Cochrane tool for assessing randomized clinical trials (RCT). Efficacy outcomes included hospitalization for heart failure and all-cause death. Safety outcomes consisted of serious adverse event (SAE) and volume depletion. Results We included data from 5 identified studies and 8775 patients (aged 64.9, female 29.8%). A total of 3930 (44.8%) patients were known to have diabetes mellitus. Compared with placebo, SGLT2 inhibitor decrease the incidence of hospitalization for heart failure (RR 0.692; 95%CI, 0.611-0.784 P<0.001), and all-cause death (RR 0.824; 95%CI, 0.736-0.922 P=0.001). The incidence of SAE in patients with a treatment of SGLT2 inhibitor was low (RR 0.869; 95%CI, 0.779-0.970 P=0.012). SGLT2 inhibitor didn’t increase the incidence of volume depletion (RR1.165, 95%CI, 0.977-1.390 P=0.089). Conclusion Our results confirm that SGLT2 inhibitor is effective and safe for patients with heart failure regardless of presence of diabetes mellitus.

scholarly journals Effects of Sodium-Glucose Cotransporter 2 on Amputation Events: A Systematic Review and Meta-Analysis of Randomized-Controlled Trials

Pharmacology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Ray Meng See ◽  
Yao Neng Teo ◽  
Yao Hao Teo ◽  
Nicholas L. Syn ◽  
Alicia Swee Yan Yip ◽  
...  
Keyword(s):  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Sodium Glucose Cotransporter ◽  
Cardiovascular Assessment ◽  
Significant Difference

<b><i>Introduction:</i></b> Sodium-glucose cotransporter 2 (SGLT2) inhibitors are increasingly utilized in the treatment of diabetes mellitus as well as therapeutic extra-glycemic effects. However, there are still concerns over complications such as amputation events, given the results from the Canagliflozin Cardiovascular Assessment Study (CANVAS) trial. Hence, we conducted a systematic review and meta-analysis of randomized-controlled trials to investigate the effect of SGLT2 inhibitors on amputation events. <b><i>Methods:</i></b> Four electronic databases (PubMed, Embase, Cochrane, and SCOPUS) were searched on November 21, 2020, for articles published from January 1, 2000, up to November 21, 2020, for studies that examined the effect of SGLT2 inhibitors on amputation events. Random-effect pair-wise meta-analysis for hazard ratios and fixed-effect Peto odds ratio meta-analysis were utilized to summarize the studies. <b><i>Results:</i></b> A total of 15 randomized-controlled trials were included with a combined cohort of 63,716 patients. We demonstrated that there was no significant difference in amputation events across different types of SGLT2 inhibitors, different baseline populations, and different duration of SGLT2 inhibitor use. <b><i>Discussion/Conclusions:</i></b> In this meta-analysis, SGLT2 inhibitors were not associated with a significant difference in amputation events.

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