Comparison of effects of SGLT-2 inhibitors and GLP-1 receptor agonists on cardiovascular and renal outcomes in type 2 diabetes mellitus patients with/without albuminuria: A systematic review and network meta-analysis

Kawai, Yasuo; Uneda, Kazushi; Yamada, Takayuki; Kinguchi, Sho; Kobayashi, Kazuo; Azushima, Kengo; Kanaoka, Tomohiko; Toya, Yoshiyuki; Wakui, Hiromichi; Tamura, Kouichi

doi:10.1016/j.diabres.2021.109146

Cited by 31 publications

(21 citation statements)

References 46 publications

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“…The clinical relevance of these results seems also highlighted by the evidence that for some outcomes the clinical benefit is consistent irrespective of the presence of type 2 diabetes [ 13 ], advanced age [ 13 , 30 ], and the background cardiorenal disease [ 12 , 15 , 31 ]. Accordingly, people with type 2 diabetes, cardiovascular disease, heart failure, or chronic kidney disease should be treated appropriately with an SGLT-2 inhibitor or GLP-1RA, even because more adults with type 2 diabetes in the US have suboptimal glycemic control now compared to 10 years ago, associated with a resurgence in vascular diabetic complications [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

The effect of DPP-4 inhibitors, GLP-1 receptor agonists and SGLT-2 inhibitors on cardiorenal outcomes: a network meta-analysis of 23 CVOTs

Giugliano

Longo

Signoriello

et al. 2022

Cardiovasc Diabetol

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Background Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose co-transporter-2 (SGLT-2) inhibitors reduce cardiorenal outcomes. We performed a network meta-analysis to compare the effect on cardiorenal outcomes among GLP-1 RAs, SGLT-2 inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors. Methods We searched the PUBMED, Embase and Cochrane databases for relevant studies published up until 10 December 2021. Cardiovascular and renal outcome trials reporting outcomes on GLP-1RA, SGLT-2 inhibitors and DPP-4 inhibitors in patients with or without type 2 diabetes mellitus were included. The primary outcome was major adverse cardiovascular events (MACE); other outcomes were cardiovascular and total death, nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for heart failure (HHF), and renal outcome. Results Twenty-three trials enrolling a total number of 181,143 participants were included. DPP-4 inhibitors did not lower the risk of any cardiorenal outcome when compared with placebo and were associated with higher risks of MACE, HHF, and renal outcome when compared with the other two drug classes. SGLT-2 inhibitors significantly reduced cardiovascular (RR = 0.88) and total (RR = 0.87) death, as compared with DPP-4 inhibitors, while GLP-1 RA reduced total death only (RR = 0.87). The comparison between GLP-1RA and SGLT-2 inhibitors showed no difference in their risks of MACE, nonfatal MI, nonfatal stroke, CV and total death; SGLT-2 inhibitors were superior to GLP-1RA in reducing the risk of HHF and the renal outcome (24% and 22% lower risk, respectively). Only GLP-1RA reduced the risk of nonfatal stroke (RR = 0.84), as compared with placebo. There was no head-to-head trial directly comparing these antidiabetic drug classes. Conclusions SGLT-2 inhibitors and GLP-1RA are superior to DPP-4 inhibitors in reducing the risk of most cardiorenal outcomes; SGLT-2 inhibitors are superior to GLP-1RA in reducing the risk of HHF and renal events; GLP-1RA only reduced the risk of nonfatal stroke. Both SGLT-2 inhibitors and GLP-1RA should be the preferred treatment for type 2 diabetes and cardiorenal diseases.

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Section: Discussionmentioning

confidence: 99%

The effect of DPP-4 inhibitors, GLP-1 receptor agonists and SGLT-2 inhibitors on cardiorenal outcomes: a network meta-analysis of 23 CVOTs

Giugliano

Longo

Signoriello

et al. 2022

Cardiovasc Diabetol

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“…Another network meta-analysis has looked into the kidney outcomes in more detail – defined as a composite of incident macroalbuminuria, ESKD, kidney function decline, and kidney-related death. 13 The study showed that both SGLT2i and GLP1RA could reduce kidney outcomes regardless of albuminuria status, with SGLT2i superior over GLP1RA in kidney outcomes. Nonetheless, the superiority of SGLT2i should be interpreted with caution as kidney outcome definitions varied across RCTs.…”

Section: Discussionmentioning

confidence: 96%

“…Although there was a network meta-analysis of nine RCTs of SGLT2i/GLP1RA vs placebo suggesting potential superiority of SGLT2i over GLP1RA in kidney outcomes in type 2 diabetes, there were certain limitations acknowledged by the authors, including varying definitions of kidney events in different RCTs included. 13 A recent Scandinavian propensity-score weighted cohort compared cardiac and kidney benefits between SGLT2i and GLP1RA users, but significant missing values of eGFR and albuminuria status limited the detailed analyses of kidney outcomes. 14 Results of such direct comparison are essential to inform diabetes care providers in offering eligible patients with type 2 diabetes the optimal anti-diabetic agents in reducing kidney outcomes.…”

Section: Introductionmentioning

confidence: 99%

Kidney outcomes associated with sodium-glucose cotransporter 2 inhibitors versus glucagon-like peptide 1 receptor agonists: A real-world population-based analysis

Lui

Tang

et al. 2022

eClinicalMedicine

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“…A recent meta-analysis 79 that included 6 CVOTs of patients with diabetes and 4 CVOTs of patients with and without diabetes found that eGFR did not alter the relative benefit of SGLT2 inhibitors for MACE and heart failure outcomes 2,74,78,[80][81][82] ; however, a greater relative benefit was reported for MACE in those with higher baseline albuminuria (ACR>300mg/g HR 0.74 95%CI 0.66, 0.84; ACR 30-300mg/g HR 0.95 [95%CI 0.82, 1.10]) ACR<30mg/g HR 0.87 [95%CI 0.77, 0.98]).…”

Section: Glp1-ramentioning

confidence: 99%

“…Contemporary meta-analysis data suggests GLP1-RA reduce the relative risk of cardiovascular disease (MACE) by 14% (HR 0.86 [95%CI 0.80-0.93]), and heart failure hospitalization by 11% (HR 0.89 [95%CI 0.82, 0.98]) compared to placebo 3 . Several large meta-analyses examining heterogenous treatment effects in placebo-controlled CVOTs have been conducted for GLP1-RA 73,80,81,[87][88][89][90][91][92][93][94] , with the majority of studies focusing on whether prior established CVD modifies the relative effect of GLP1-RA on MACE and/or heart failure. Two meta-analyses reported the relative MACE benefit of GLP-RA may be restricted to those with established CVD 80,87 , the largest of which included 7 RCTs and reported a 14% relative risk reduction with GLP1-RA specific to individuals with established CVD (with CVD: HR 0.86 [95%CI 0.80, 0.93]; at high-risk of CVD: HR 0.94 [95% CI 0.82, 1.07]) 80 .…”

Section: Glp1-ra: Evidence From Clinical Trialsmentioning

confidence: 99%

Precision medicine in type 2 diabetes: A systematic review of treatment effect heterogeneity for GLP1-receptor agonists and SGLT2-inhibitors

Young

McInnes

Massey

et al. 2023

Preprint

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Background: A precision medicine approach in type 2 diabetes requires identification of clinical and biological features that are reproducibly associated with differences in clinical outcomes with specific anti-hyperglycaemic therapies. Robust evidence of such treatment effect heterogeneity could support more individualized clinical decisions on optimal type 2 diabetes therapy. Methods: We performed a pre-registered systematic review of meta-analysis studies, randomized control trials, and observational studies evaluating clinical and biological features associated with heterogenous treatment effects for SGLT2-inhibitor and GLP1-receptor agonist therapies, considering glycaemic, cardiovascular, and renal outcomes. Results: After screening 5,686 studies, we included 101 studies of SGLT2-inhibitors and 75 studies of GLP1-receptor agonists in the final systematic review. The majority of papers had methodological limitations precluding robust assessment of treatment effect heterogeneity. For glycaemic outcomes, most cohorts were observational, with multiple analyses identifying lower renal function as a predictor of lesser glycaemic response with SGLT2-inhibitors and markers of reduced insulin secretion as predictors of lesser response with GLP1-receptor agonists. For cardiovascular and renal outcomes, the majority of included studies were post-hoc analyses of randomized control trials (including meta-analysis studies) which identified limited clinically relevant treatment effect heterogeneity. Conclusions: Current evidence on treatment effect heterogeneity for SGLT2-inhibitor and GLP1-receptor agonist therapies is limited, likely reflecting the methodological limitations of published studies. Robust and appropriately powered studies are required to understand type 2 diabetes treatment effect heterogeneity and evaluate the potential for precision medicine to inform future clinical care.

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Comparison of effects of SGLT-2 inhibitors and GLP-1 receptor agonists on cardiovascular and renal outcomes in type 2 diabetes mellitus patients with/without albuminuria: A systematic review and network meta-analysis

Cited by 31 publications

References 46 publications

The effect of DPP-4 inhibitors, GLP-1 receptor agonists and SGLT-2 inhibitors on cardiorenal outcomes: a network meta-analysis of 23 CVOTs

The effect of DPP-4 inhibitors, GLP-1 receptor agonists and SGLT-2 inhibitors on cardiorenal outcomes: a network meta-analysis of 23 CVOTs

Kidney outcomes associated with sodium-glucose cotransporter 2 inhibitors versus glucagon-like peptide 1 receptor agonists: A real-world population-based analysis

Precision medicine in type 2 diabetes: A systematic review of treatment effect heterogeneity for GLP1-receptor agonists and SGLT2-inhibitors

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