Effects of glucose-lowering agents on surrogate endpoints and hard clinical renal outcomes in patients with type 2 diabetes

Scheen, André

doi:10.1016/j.diabet.2018.10.003

Cited by 43 publications

(36 citation statements)

References 162 publications

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“…GLP‐1RAs and SGLT‐2is are very effective medications that continue to be clearly indicated in the management of type 2 diabetes. Both classes can reduce haemoglobin A1c levels and cause weight loss, which subsequently may improve insulin sensitivity without hypoglycaemia and may have renal protective effects . A thorough discussion and evaluation regarding the appropriateness of the medication to be added to metformin remains crucial in black patients with type 2 diabetes, and the National Institute of Diabetes and Digestive and Kidney diseases‐funded GRADE trial may inform this discussion .…”

Section: Discussionmentioning

confidence: 99%

Do GLP‐1RAs and SGLT‐2is reduce cardiovascular events in black patients with type 2 diabetes? A systematic review and meta‐analysis

Mishriky

Powell

Wittwer

et al. 2019

Diabetes Obesity Metabolism

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Aims While recent cardiovascular safety trials (CVST) concerning newer diabetes medications included mostly white participants, results are being generalized to all races in recent guidelines. This raises a controversial question regarding the appropriateness of applying CVST data to black patients with type 2 diabetes. Materials and methods We searched for randomized trials comparing diabetes medications to placebo in type 2 diabetes and investigated three‐ or four‐point major adverse cardiovascular events (MACE). Data concerning black patients were then extracted. As the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) updated their recommendations for patients with established cardiovascular risk based on the CVST showing cardiovascular benefit, we performed a sensitivity analysis by including those trials only. Results A total of 11 trials were included, investigating a glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) in five, a sodium‐glucose co‐transporter‐2 inhibitor (SGLT‐2i) in two and dipeptidyl peptidase‐4 inhibitors (DPP‐4i) in four. Of the 102 416 participants enrolled in the included trials, only 4601 were black (4.5%). Pooled results showed no significant difference in the incidence of MACE among diabetes medications (GLP‐1RA, SGLT‐2i or DPP‐4i) and placebo in black patients with type 2 diabetes (relative risk [RR] [95% CI], 0.94 [0.77,1.16]). Restricting the analysis to different classes of diabetes medication, the results remained non‐significant. Restricting the analysis to CVST with significant outcomes, the results remained non‐significant (RR [95% CI], 0.97 [0.68,1.39]). Conclusions Given that black patients with type 2 diabetes were not well represented in CVSTs and such trials were underpowered to evaluate racial differences, it remains unclear whether GLP‐1RAs or SGLT‐2is would reduce cardiovascular risk in such patients, and additional studies targeting black patients are urgently needed.

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Section: Discussionmentioning

confidence: 99%

Do GLP‐1RAs and SGLT‐2is reduce cardiovascular events in black patients with type 2 diabetes? A systematic review and meta‐analysis

Mishriky

Powell

Wittwer

et al. 2019

Diabetes Obesity Metabolism

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“…The interest was even increased following the demonstration of the remarkable renoprotective effect of blockers of the reninangiotensin system [35]. Both SGT2is and GLP-1RAs, added to RAS blockers, have been shown to reduce microalbuminuria and proteinuria in patients with T2DM, although SGLT2is appear to exert a stronger protective effect on hard clinical outcomes [36].…”

Section: Need For Detection Of Renal Diseasementioning

confidence: 99%

“…There is no restriction in the use of GLP-1RAs in patients with moderate to severe CKD [40], yet this pharmacological class has not proven its ability to avoid the progression of renal disease, at least with a rather short follow up of <4 years, in contrast to the impressive demonstration by SGLT2is [36].…”

Section: Need For Detection Of Renal Diseasementioning

confidence: 99%

“…As emphasized in a report from the European Society of Cardiology Cardiovascular Roundtable, addressing cardiovascular risk in T2DM requires a better collaboration between diabetologists and cardiologists [21]. Considering the increasing importance of CKD in T2DM [4,5,35] and the specific action of SGLT2is to slow down the progression of renal disease [36], a closer collaboration between endocrinologists and nephrologists may also become mandatory [43].…”

Section: Need For a Collaboration Between Diabetologists Cardiologismentioning

confidence: 99%

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Series: Implications of the recent CVOTs in type 2 diabetes

Scheen

2020

Diabetes Research and Clinical Practice

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“…Thus, one of the treatment goals for T2DM is reduction of hyperglycemia to delay onset of and slow progression of microvascular complications, including nephropathy . Recent research efforts have increasingly focused on the renal effects of glucose‐lowering therapies, with the greatest benefits for renal outcomes reported for sodium‐glucose cotransporter‐2 inhibitors and glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) …”

Section: Introductionmentioning

confidence: 99%

Review of glucagon‐like peptide‐1 receptor agonists for the treatment of type 2 diabetes mellitus in patients with chronic kidney disease and their renal effects

Sloan

2019

Journal of Diabetes

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Type 2 diabetes mellitus (T2DM) is the most common cause of chronic kidney disease (CKD), and when it causes CKD it is collectively referred to as diabetic kidney disease. One of the newer therapies for managing hyperglycemia is the glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) drug class. This review summarizes the effects of GLP‐1RAs in patients with T2DM with CKD and evidence for renoprotection with GLP‐1RAs using data from observational studies, prospective clinical trials, post hoc analyses, and meta‐analyses. Evidence from some preclinical studies was also reviewed. Taken together, subgroup analyses of patients with varying degrees of renal function demonstrated that glycemic control with GLP‐1RAs was not markedly less effective in patients with mild or moderate renal impairment vs that in patients with normal function. GLP‐1RAs were associated with improvements in some cardiorenal risk factors, including systolic blood pressure and body weight. Furthermore, several large cardiovascular outcome studies showed reduced risks of composite renal outcomes, mostly driven by a reduction in macroalbuminuria, suggesting potential renoprotective effects of GLP‐1RAs. In conclusion, GLP‐1RAs effectively reduced hyperglycemia in patients with mild or moderately impaired kidney function in the limited number of studies to date. GLP‐1RAs may be considered in combination with other glucose‐lowering medications because of their ability to lower glucose in a glucose‐dependent manner, lowering their risk for hypoglycemia, while improving some cardiorenal risk factors. Potential renoprotective effects of GLP‐1RAs, and their renal mechanisms of action, warrant further investigation.

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Effects of glucose-lowering agents on surrogate endpoints and hard clinical renal outcomes in patients with type 2 diabetes

Abstract: Please cite this article in press as: Scheen AJ. Effects of glucose-lowering agents on surrogate endpoints and hard clinical renal outcomes in patients with type 2 diabetes. Diabetes Metab (2018),

Cited by 43 publications

References 162 publications

Do GLP‐1RAs and SGLT‐2is reduce cardiovascular events in black patients with type 2 diabetes? A systematic review and meta‐analysis

Do GLP‐1RAs and SGLT‐2is reduce cardiovascular events in black patients with type 2 diabetes? A systematic review and meta‐analysis

Series: Implications of the recent CVOTs in type 2 diabetes

Review of glucagon‐like peptide‐1 receptor agonists for the treatment of type 2 diabetes mellitus in patients with chronic kidney disease and their renal effects

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