TY - JOUR
T1 - Effects of DPP-4 inhibitors, GLP-1 receptor agonists, SGLT-2 inhibitors and sulphonylureas on mortality, cardiovascular and renal outcomes in type 2 diabetes
T2 - A network meta-analyses-driven approach
AU - Brønden, Andreas
AU - Christensen, Mikkel Bring
AU - Glintborg, Dorte
AU - Snorgaard, Ole
AU - Kofoed-Enevoldsen, Allan
AU - Madsen, Gitte Krogh
AU - Toft, Katja
AU - Kristensen, Jette Kolding
AU - Højlund, Kurt
AU - Hansen, Troels Krarup
AU - Søndergaard, Esben
AU - Hansen, Katrine Bagge
PY - 2023/8
Y1 - 2023/8
N2 - AIMS: The aim of our meta-analyses was to compare the effects of glucose-lowering drugs on mortality, cardiovascular and renal endpoints for a range of type 2 diabetes (T2D) subgroups defined by their specific cardiovascular risk profile.METHODS: Meta-analyses comparing drugs within the classes of GLP-1RAs and SGLT-2 inhibitors were performed and compared to sulphonylureas and DPP-4 inhibitors with available cardiovascular outcome trials. The comparison between the different classes of glucose-lowering drugs included analyses of T2D populations with low risk and high risk for cardiovascular disease including populations with established cardiovascular disease and/or kidney disease. Outcomes included mortality, major cardiovascular adverse events (MACE), hospitalisation for heart failure (HHF) and a composite renal endpoint as applied in the underlying clinical trials.RESULTS: SGLT-2 inhibitors and GLP-1RAs showed beneficial effects on mortality and MACE compared to the classes of DPP-4 inhibitors and sulphonylureas. SGLT-2 inhibitors were shown to be the most effective treatment in terms of HHF and kidney disease. Metformin was used as background therapy for the vast majority of participants in all included studies. Overall, the absolute effects of SGLT-2 inhibitors and GLP-1RAs on these important outcomes were evident for patients with established or at high risk for cardiovascular disease but limited for the low-risk subgroup.CONCLUSIONS: The findings from our analyses substantiate the relevance of treatment with SGLT-2 inhibitors or GLP-1RAs as add-on to metformin in patients with T2D and a high risk for cardiovascular disease, and furthermore, support the recommendation for SGLT-2 inhibitor treatment in patients with T2D and heart failure or established kidney disease.
AB - AIMS: The aim of our meta-analyses was to compare the effects of glucose-lowering drugs on mortality, cardiovascular and renal endpoints for a range of type 2 diabetes (T2D) subgroups defined by their specific cardiovascular risk profile.METHODS: Meta-analyses comparing drugs within the classes of GLP-1RAs and SGLT-2 inhibitors were performed and compared to sulphonylureas and DPP-4 inhibitors with available cardiovascular outcome trials. The comparison between the different classes of glucose-lowering drugs included analyses of T2D populations with low risk and high risk for cardiovascular disease including populations with established cardiovascular disease and/or kidney disease. Outcomes included mortality, major cardiovascular adverse events (MACE), hospitalisation for heart failure (HHF) and a composite renal endpoint as applied in the underlying clinical trials.RESULTS: SGLT-2 inhibitors and GLP-1RAs showed beneficial effects on mortality and MACE compared to the classes of DPP-4 inhibitors and sulphonylureas. SGLT-2 inhibitors were shown to be the most effective treatment in terms of HHF and kidney disease. Metformin was used as background therapy for the vast majority of participants in all included studies. Overall, the absolute effects of SGLT-2 inhibitors and GLP-1RAs on these important outcomes were evident for patients with established or at high risk for cardiovascular disease but limited for the low-risk subgroup.CONCLUSIONS: The findings from our analyses substantiate the relevance of treatment with SGLT-2 inhibitors or GLP-1RAs as add-on to metformin in patients with T2D and a high risk for cardiovascular disease, and furthermore, support the recommendation for SGLT-2 inhibitor treatment in patients with T2D and heart failure or established kidney disease.
KW - effectiveness
KW - cardiovascular outcomes
KW - mortality
KW - GLP-1 receptor agonist
KW - renal outcomes
KW - network meta-analysis
KW - sulphonylureas
KW - SGLT2 inhibitor
KW - DPP-IV inhibitor
KW - Cardiovascular Diseases
KW - Humans
KW - Glucose
KW - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
KW - Diabetes Mellitus, Type 2/complications
KW - Sulfonylurea Compounds/therapeutic use
KW - Heart Failure/drug therapy
KW - Metformin/therapeutic use
KW - Glucagon-Like Peptide-1 Receptor/agonists
KW - Hypoglycemic Agents/therapeutic use
KW - Network Meta-Analysis
KW - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
UR - http://www.scopus.com/inward/record.url?scp=85163128010&partnerID=8YFLogxK
U2 - 10.1111/dme.15157
DO - 10.1111/dme.15157
M3 - Review
C2 - 37249579
SN - 1464-5491
VL - 40
JO - Diabetic medicine : a journal of the British Diabetic Association
JF - Diabetic medicine : a journal of the British Diabetic Association
IS - 8
M1 - e15157
ER -