SGLT-2 inhibitors as cardio-renal protective agents

Genchi, Valentina Annamaria; Giorgino, Francesco

doi:10.1016/j.metabol.2021.154937

Cited by 28 publications

(22 citation statements)

References 67 publications

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“…No significant difference in hospitalization for HF was found between the two cohorts, whereas in previous in RWS SGLT-2i seem to be associated with lower risk of heart failure and total mortality comparing new users of SGLT-2i and GLP-1RA [ 17 – 19 ]. SGLT-2i displayed an unparalleled benefit on HF-related outcomes in randomized controlled trials regardless of the baseline cardio-renal risk of the enrolled population [ 29 ]; accordingly, a meta-analysis of RWS showed that SGLT-2i were more effective than GLP-1RA on prevention of HF worsening [ 30 ]. On the other hand, albeit to a lesser extent, GLP-1RA have also been proven beneficial, significantly reducing HF hospitalization by 11% compared to placebo in CVOT [ 2 ] and by 12% compared to other glucose-lowering drugs except for SGLT-2i in RWS [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Effectiveness and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in type 2 diabetes: an Italian cohort study

Baviera

Foresta

Colacioppo

et al. 2022

Cardiovasc Diabetol

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Background GLP-1 receptor agonists (GLP-1 RA) and SGLT-2 inhibitors (SGLT-2i) have shown to reduce the risk of major adverse cardiovascular events (MACE), death and worsening nephropathy when added to standard of care. However, these two dug classes differ in efficacy and safety. We compared the effectiveness and safety profile of GLP-1 RA and SGLT-2i in a large and unselected cohort of patients with type 2 diabetes resident in Lombardy from 2015 to 2020. Methods Using linkable administrative health databases, we included patients aged 50 years and older initiating GLP-1 RA or SGLT-2i. Clinical events were: death, hospital admission for myocardial infarction (MI), stroke, heart failure (HF), and renal disease as individual and composite outcomes (MACE-3: all cause-death, non-fatal MI, non-fatal stroke; MACE-4: MACE-3 plus unstable angina). Outcomes were evaluated separately in subjects with and without previous cardiovascular (CV) diseases. Treatments were compared using Cox proportional hazards regression model after Propensity Score Matching (PSM) in both intention-to-treat (ITT) and per protocol (PP) analyses. Serious adverse events were also evaluated. Results The analysis comprised 20,762 patients per cohort. The ITT analysis showed a significant risk reduction for non-fatal MI (HR 0.77; CI 95% 0.66–0.90), MACE-3 (HR 0.91; CI 95% 0.84–0.98), and MACE-4 (HR 0.92; CI 95% 0.86–0.99) in GLP-1RA compared with SGLT-2i users, while no difference was reported in the incidence of HF hospitalization and stroke between the two cohorts. Similar benefits were found in the subgroup of patients without previous CV diseases only. PP analysis largely confirmed the main results. The incidence of serious adverse events was low in both cohorts (< 1%). Conclusions GLP-1RA showed to be equally safe and more effective than SGLT-2i in reducing the risk of MACE-3, MACE-4 and MI. This study adds to the growing body of real-world evidence addressing the specific clinical properties of GLP-1RA and SGLT-2i in everyday practice to tailor treatment to the individual patient.

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Section: Discussionmentioning

confidence: 99%

Effectiveness and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in type 2 diabetes: an Italian cohort study

Baviera

Foresta

Colacioppo

et al. 2022

Cardiovasc Diabetol

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“…In recent studies, treatment with SGLT-2i and GLP-1 RA proved to reduce the risk for a combined major adverse cardiovascular event endpoint (including cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) [ 60 , 71 ]. In the CREDENCE and the DAPA-CKD trials, treatment with canagliflozin and dapagliflozin were shown to reduce risks of substantial eGFR decline or kidney failure with a primary kidney disease outcome in adults with T2D who had DKD.…”

Section: Discussionmentioning

confidence: 99%

New strategies to improve clinical outcomes for diabetic kidney disease

Forst

Mathieu

Giorgino

et al. 2022

BMC Med

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Background Diabetic kidney disease (DKD), the most common cause of kidney failure and end-stage kidney disease worldwide, will develop in almost half of all people with type 2 diabetes. With the incidence of type 2 diabetes continuing to increase, early detection and management of DKD is of great clinical importance. Main body This review provides a comprehensive clinical update for DKD in people with type 2 diabetes, with a special focus on new treatment modalities. The traditional strategies for prevention and treatment of DKD, i.e., glycemic control and blood pressure management, have only modest effects on minimizing glomerular filtration rate decline or progression to end-stage kidney disease. While cardiovascular outcome trials of SGLT-2i show a positive effect of SGLT-2i on several kidney disease-related endpoints, the effect of GLP-1 RA on kidney-disease endpoints other than reduced albuminuria remain to be established. Non-steroidal mineralocorticoid receptor antagonists also evoke cardiovascular and kidney protective effects. Conclusion With these new agents and the promise of additional agents under clinical development, clinicians will be more able to personalize treatment of DKD in patients with type 2 diabetes.

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“…These medications reduce hyperglycemia (Hb1Ac reduction of −0.8 ± 1.4%) through the inhibition of glucose reabsorption in the proximal convoluted tubule of the kidney and the resulting increase in glycosuria (10)(11)(12). Notably, recent findings have described the pleiotropic effects of SGLT-2is in terms of cardioprotection as well as renoprotection (13)(14)(15)(16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Mini Review: Effect of GLP-1 Receptor Agonists and SGLT-2 Inhibitors on the Growth Hormone/IGF Axis

et al. 2022

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Accumulating evidence supports the early use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium glucose transporter-2 inhibitors (SGLT-2is) for the treatment of type 2 diabetes. Indeed, these compounds exert numerous pleiotropic actions that favorably affect metabolism and diabetes comorbidities, showing an additional effect beyond glucose control. Although a substantial amount of knowledge has been generated regarding the mechanism of action of both drug classes, much remains to be understood. Growth hormone (GH) is an important driver for multiple endocrine responses involving changes in glucose and lipid metabolism, and affects several tissues and organs (e.g., bone, heart). It acts directly on several target tissues, including skeletal muscle and bone, but several effects are mediated indirectly by circulating (liver-derived) or locally produced IGF-1. In consideration of the multiple metabolic and cardiovascular effects seen in subjects treated with GLP-1RAs and SGLT-2is (e.g., reduction of hyperglycemia, weight loss, free/fat mass and bone remodeling, anti-atherosclerosis, natriuresis), it is reasonable to speculate that GH and IGF-1 may play a about a relevant role in this context. This narrative mini-review aims to describe the involvement of the GH/IGF-1/IGF-1R axis in either mediating or responding to the effects of each of the two drug classes.

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SGLT-2 inhibitors as cardio-renal protective agents

Cited by 28 publications

References 67 publications

Effectiveness and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in type 2 diabetes: an Italian cohort study

Effectiveness and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in type 2 diabetes: an Italian cohort study

New strategies to improve clinical outcomes for diabetic kidney disease

Mini Review: Effect of GLP-1 Receptor Agonists and SGLT-2 Inhibitors on the Growth Hormone/IGF Axis

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