scholarly journals Glucagon-like Peptide-1 Receptor Agonists versus Sodium-Glucose Cotransporter Inhibitors for Treatment of T2DM

2020 ◽  
Vol 4 (5) ◽  
Author(s):  
Alexis McKee ◽  
Ali Al-Khazaali ◽  
Stewart G Albert
Keyword(s):  
Adverse Events ◽  
Relative Rate ◽  
Major Adverse Cardiovascular Events ◽  
Serious Adverse Events ◽  
Similar Reduction ◽  
Renal Outcomes ◽  
Receptor Agonists ◽  
Sodium Glucose Cotransporter ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Context Cardiovascular outcome trials (CVOT) of glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) demonstrated reduction of major adverse cardiovascular events (MACE), cardiovascular deaths (CVD), and renal outcomes. Objective Assist in the prescribing decision regarding severity of illness and risk for adverse events. Design Meta-analysis of the major CVOT and previous meta-analyses. Main Outcome Measures Six trials of GLP-1 RA (51 762 subjects) and 4 trials of SGLT2i (33 457 subjects) showed both drug classes reduced MACE and CVD versus controls, with neither class preferred (comparison GLP1-RA vs SGLT2i: relative rate [rr] MACE 1.04, 95% confidence interval [CI] 0.94, 1.16, P = ns; rr CVD 1.04, 95% CI 0.87, 1.24, P = ns). Hospitalization for heart failure (HHF) improved with SGLT2i (rr 0.68, CI 0.61, 0.76, P < 0.001) but not with GLP-1 RA, (rr 0.93, CI 0.86,1.03, P = ns). Meta-regression suggested benefits of the SGLT2i on CVD and HHF were accentuated with the underlying rate of MACE in the cohort (i.e., >10 events/1000pt*year). GLP-1 RA and SGLT2i showed reduction in renal outcomes (GLP-1 RA rr 0.83, CI 0.75, 0.91, p ≤ 0.001, SGLT2i rr 0.67, CI 0.57, 0.79, P < 0.001) without a preferential difference (GLP-1 RA vs SGLT2i, rr 1.24, CI 0.95, 1.61, P = ns; relative difference (rd) 0.005, CI -0.011, 0.021, P = ns). Serious adverse events for SGLT2i were mycotic genital infections in women (number needed to harm [NNH] = 13 and diabetic ketoacidosis NNH = 595. Gastrointestinal intolerance was the serious adverse event in the GLP1-RA class (NNH = 35). Conclusion GLP-1 RA and SGLT2i classes showed similar reduction in MACE, CVD, and renal outcomes. SGLT2i have advantages over GLP-1 RA in reduction in HHF.

scholarly journals SUN-618 Decision Analysis for Glucagon-Like Peptide Receptor Agonists vs. Sodium-Glucose cotransporter2 Inhibitors in Type 2 Diabetes Mellitus

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Ali Al khazaali ◽  
Alexis Mckee ◽  
Anjul Sharma ◽  
Stewart Albert
Keyword(s):  
Adverse Events ◽  
Disease Risk ◽  
Relative Rate ◽  
Cardiovascular Disease Risk ◽  
Systemic Review ◽  
Major Adverse Cardiovascular Events ◽  
Number Needed To Treat ◽  
Serious Adverse Events ◽  
Similar Reduction ◽  
Glucagon Like Peptide

Abstract Background: Cardiovascular outcome trials (CVOT) of glucagon-like peptide-1receptor agonists (GLP-1 RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2i) demonstrated reduction of major adverse cardiovascular events (MACE), cardiovascular deaths (CVD), and renal outcomes (RO). Objective. Evaluation of data to assist in the prescribing decision with regard to severity of illness and risk for adverse events. Study Design: Systemic review of the major CVOT and previous meta-analyses. Main Outcome Measures: Analysis of six trials on GLP-1 RA and 4 trials on SGLT2i, showed both drug classes reduced MACE and CVD compared to controls, with neither class preferred (comparison GLP1-RA vs SGLT2i: (relative rate, rr MACE= 1.09, 95%CI;0.98,1.22, p= 0.129; rr, CVD =1.04, CI;0.87,1.24, p=0.657). Hospitalization for heart failure (HHF) improved with SGLT2i (rr=0.68, CI; 0.61,0.76, p<0.001) but not with GLP-1 RA, (rr = 0.94, CI; 0.86,1.03, p=0.17). Both GLP-1 RA and SGLT2i showed significant reduction in RO (GLP-1RA, rr=0.83, CI; 0.75,0.912, p=<0.001, SGLT2i, rr=0.0.67, CI; 0.57,0.79, p=0.001) without a preferential difference between the classes (GLP-1 RA vs SGLT2i, relative difference (rd) =0.005, CI;-0.011,0.021, p=0.532, number needed to treat (NNT)=200). Serious adverse events (SAE) for SGLT2i were predominantly mycotic genital infections in women (number needed to harm (NNH) =13 and diabetic ketoacidosis NNH=595. Gastrointestinal intolerance was the major SAE in the GLP1-RA class (NNH=35). Conclusion: Both GLP-1 RA and SGLT2i classes showed similar reduction in MACE, CVD, and RO. SGLT2i have advantages over GLP-1 RA in reduction in HHF especially in those with more severe cardiovascular disease risk.

scholarly journals How Do SGLT2 (Sodium-Glucose Cotransporter 2) Inhibitors and GLP-1 (Glucagon-Like Peptide-1) Receptor Agonists Reduce Cardiovascular Outcomes?

2020 ◽  
Vol 40 (3) ◽  
pp. 506-522 ◽  
Author(s):  
Matthew M.Y. Lee ◽  
Mark C. Petrie ◽  
John J.V. McMurray ◽  
Naveed Sattar
Keyword(s):  
Diabetes Mellitus ◽  
Mechanisms Of Action ◽  
Left Ventricular ◽  
Sglt2 Inhibitors ◽  
Left Ventricular Ejection ◽  
Cardiac Effects ◽  
Receptor Agonists ◽  
Sodium Glucose Cotransporter ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Objective: There is substantial interest in how GLP-1RA (glucagon-like peptide-1 receptor agonists) and SGLT2 (sodium-glucose cotransporter 2) inhibitors reduce cardiovascular and renal events; yet, robust mechanistic data in humans remain sparse. We conducted a narrative review of published and ongoing mechanistic clinical trials investigating the actions of SGLT2 inhibitors and GLP-1RAs to help the community appreciate the extent of ongoing work and the variety and design of such trials. Approach and Results: To date, trials investigating the mechanisms of action of SGLT2 inhibitors have focused on pathways linked to glucose metabolism and toxicity, hemodynamic/volume, vascular and renal actions, and cardiac effects, including those on myocardial energetics. The participants studied have included those with established cardiovascular disease (including coronary artery disease and heart failure), liver disease, renal impairment, obesity, and hypertension; some of these trials have enrolled patients both with and without type 2 diabetes mellitus. GLP-1RA mechanistic trials have focused on glucose-lowering, insulin-sparing, weight reduction, and blood pressure–lowering effects, as well as possible direct vascular, cardiac, and renal effects of these agents. Very few mechanisms of action of SGLT2 inhibitors or GLP-1RAs have so far been convincingly demonstrated. One small trial (n=97) of SGLT2 inhibitors has investigated the cardiac effects of these drugs, where a small reduction in left ventricular mass was found. Data on vascular effects are limited to one trial in type 1 diabetes mellitus, which suggests some beneficial actions. SGLT2 inhibitors have been shown to reduce liver fat. We highlight the near absence of mechanistic data to explain the beneficial effects of SGLT2 inhibitors in patients without diabetes mellitus. GLP-1RAs have not been found to have major cardiovascular mechanisms of action in the limited, completed trials. Conflicting data around the impact on infarct size have been reported. No effect on left ventricular ejection fraction has been demonstrated. Conclusions: We have tabulated the extensive ongoing mechanistic trials that will report over the coming years. We report 2 exemplar ongoing mechanistic trials in detail to give examples of the designs and techniques employed. The results of these many ongoing trials should help us understand how SGLT2 inhibitors and GLP-1RAs improve cardiovascular and renal outcomes and may also identify unexpected mechanisms suggesting novel therapeutic applications.

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