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Original investigation
Hiromichi Wakui
Corresponding Author
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Background Emerging evidence suggests that sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with decreased risk of cardiovascular and renal events in type 2 diabetes mellitus (DM) patients. However, no study to date has compared the effect of SGLT-2 inhibitors with that of GLP-1 RAs in type 2 DM patients with chronic kidney disease (CKD). We herein investigated the benefits of SGLT-2 inhibitors and GLP-1 RAs in CKD patients.
Methods We performed a systematic literature search through November 2020. We selected randomized control trials that compared the risk of major adverse cardiovascular events (MACE) and a composite of renal outcomes. We performed a network meta-analysis to compare SGLT-2 inhibitors with GLP-1 RAs indirectly. Risk ratios (RRs) with corresponding 95% confidence intervals (CI) were synthesized.
Results Thirteen studies were selected with a total of 32,949 patients. SGLT-2 inhibitors led to a risk reduction in MACE and renal events (RR [95 %CI]; 0.85 [0.75-0.96] and 0.68 [0.59-0.78], respectively). However, GLP-1 RAs did not reduce the risk of cardiovascular or renal adverse events (RR 0.91 [0.80-1.04] and 0.86 [0.72-1.03], respectively). Compared to GLP-1 RAs, SGLT-2 inhibitors did not demonstrate a significant difference in MACE (RR 0.94 [0.78-1.12]), while SGLT-2 inhibitors were associated with a lower risk of renal events compared to GLP-1 RAs (RR 0.79 [0.63-0.99]). A sensitivity analysis revealed that GLP-1 analogues significantly decreased MACE when compared to placebo treatment (RR 0.81 [0.69-0.95]), while exendin-4 analogues did not (RR 1.03 [0.88-1.20]).
Conclusions In patients with type 2 DM and CKD, SGLT-2 inhibitors were associated with a decreased risk of cardiovascular and renal events, but GLP-1 RAs were not. SGLT-2 inhibitors significantly decreased the risk of renal events compared to GLP-1 RAs. Among GLP-1 RAs, GLP-1 analogues showed a positive impact on cardiovascular and renal outcomes, while exendin-4 analogues did not.
Keywords
SGLT2 inhibitors, GLP-1 receptor agonist, meta-analysis, Cardiovascular disease, renal outcomes, diabetes mellitus, chronic kidney disease
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CURRENT STATUS: Published
View the published article at Cardiovascular Diabetology.
Version 3
Posted 30 Dec, 2020
No community comments so far
Editorial decision: Accept
On 13 Dec, 2020
Editor assigned
On 08 Dec, 2020
Submission checks complete
On 08 Dec, 2020
Editor invited
On 08 Dec, 2020
No comments provided
Editorial decision: Major Revision
On 15 Nov, 2020
Review #3 received
Received 13 Nov, 2020
Review #1 received
Received 09 Nov, 2020
Reviewer #3 agreed
On 08 Nov, 2020
Reviewer #2 agreed
On 08 Nov, 2020
Review #2 received
Received 08 Nov, 2020
Editor assigned
On 05 Nov, 2020
Reviewers invited
Invitations sent on 05 Nov, 2020
Reviewer #1 agreed
On 05 Nov, 2020
Submission checks complete
On 05 Nov, 2020
Editor invited
On 05 Nov, 2020
No comments provided
Review #1 received
Received 30 Sep, 2020
Review #3 received
Received 30 Sep, 2020
Editorial decision: Major Revision
On 30 Sep, 2020
Review #2 received
Received 29 Sep, 2020
Reviewer #3 agreed
On 11 Sep, 2020
Reviewers invited
Invitations sent on 10 Sep, 2020
Reviewer #1 agreed
On 10 Sep, 2020
Reviewer #2 agreed
On 10 Sep, 2020
Editor assigned
On 08 Sep, 2020
Editor invited
On 07 Sep, 2020
Submission checks complete
On 06 Sep, 2020
First submitted
On 24 Aug, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cardiac & Cardiovascular Systems
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See the published version of this preprint at Cardiovascular Diabetology.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Original investigation
Hiromichi Wakui
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Cardiovascular Diabetology.
Version 3
Posted 30 Dec, 2020
No community comments so far
Editorial decision: Accept
On 13 Dec, 2020
Editor assigned
On 08 Dec, 2020
Submission checks complete
On 08 Dec, 2020
Editor invited
On 08 Dec, 2020
No comments provided
Editorial decision: Major Revision
On 15 Nov, 2020
Review #3 received
Received 13 Nov, 2020
Review #1 received
Received 09 Nov, 2020
Reviewer #3 agreed
On 08 Nov, 2020
Reviewer #2 agreed
On 08 Nov, 2020
Review #2 received
Received 08 Nov, 2020
Editor assigned
On 05 Nov, 2020
Reviewers invited
Invitations sent on 05 Nov, 2020
Reviewer #1 agreed
On 05 Nov, 2020
Submission checks complete
On 05 Nov, 2020
Editor invited
On 05 Nov, 2020
No comments provided
Review #1 received
Received 30 Sep, 2020
Review #3 received
Received 30 Sep, 2020
Editorial decision: Major Revision
On 30 Sep, 2020
Review #2 received
Received 29 Sep, 2020
Reviewer #3 agreed
On 11 Sep, 2020
Reviewers invited
Invitations sent on 10 Sep, 2020
Reviewer #1 agreed
On 10 Sep, 2020
Reviewer #2 agreed
On 10 Sep, 2020
Editor assigned
On 08 Sep, 2020
Editor invited
On 07 Sep, 2020
Submission checks complete
On 06 Sep, 2020
First submitted
On 24 Aug, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cardiac & Cardiovascular Systems
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Cardiovascular Diabetology.
Background Emerging evidence suggests that sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with decreased risk of cardiovascular and renal events in type 2 diabetes mellitus (DM) patients. However, no study to date has compared the effect of SGLT-2 inhibitors with that of GLP-1 RAs in type 2 DM patients with chronic kidney disease (CKD). We herein investigated the benefits of SGLT-2 inhibitors and GLP-1 RAs in CKD patients.
Methods We performed a systematic literature search through November 2020. We selected randomized control trials that compared the risk of major adverse cardiovascular events (MACE) and a composite of renal outcomes. We performed a network meta-analysis to compare SGLT-2 inhibitors with GLP-1 RAs indirectly. Risk ratios (RRs) with corresponding 95% confidence intervals (CI) were synthesized.
Results Thirteen studies were selected with a total of 32,949 patients. SGLT-2 inhibitors led to a risk reduction in MACE and renal events (RR [95 %CI]; 0.85 [0.75-0.96] and 0.68 [0.59-0.78], respectively). However, GLP-1 RAs did not reduce the risk of cardiovascular or renal adverse events (RR 0.91 [0.80-1.04] and 0.86 [0.72-1.03], respectively). Compared to GLP-1 RAs, SGLT-2 inhibitors did not demonstrate a significant difference in MACE (RR 0.94 [0.78-1.12]), while SGLT-2 inhibitors were associated with a lower risk of renal events compared to GLP-1 RAs (RR 0.79 [0.63-0.99]). A sensitivity analysis revealed that GLP-1 analogues significantly decreased MACE when compared to placebo treatment (RR 0.81 [0.69-0.95]), while exendin-4 analogues did not (RR 1.03 [0.88-1.20]).
Conclusions In patients with type 2 DM and CKD, SGLT-2 inhibitors were associated with a decreased risk of cardiovascular and renal events, but GLP-1 RAs were not. SGLT-2 inhibitors significantly decreased the risk of renal events compared to GLP-1 RAs. Among GLP-1 RAs, GLP-1 analogues showed a positive impact on cardiovascular and renal outcomes, while exendin-4 analogues did not.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
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