Compelling evidence for SGLT2 inhibitors and GLP-1 receptor agonists as first-line therapy in patients with diabetes at very high/high cardiovascular risk

Marx, N; Grant, Peter J.; Cosentino, Francesco

doi:10.1093/eurheartj/ehz853

Cited by 12 publications

(7 citation statements)

References 6 publications

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“…Newer anti-diabetic agent sodium glucose cotransporter 2 (SGLT2) inhibitor (SGLT2i) is very useful due to its potential benefits on HF and diabetic nephropathy (Heerspink et al, 2020;Marx, Grant, & Cosentino, 2020). Thus the combination of SGLT2i and DPP4i is used more and more widely in T2DM patients.…”

Section: Dpp4/cd26 Inhibition On Infectious Diseasesmentioning

confidence: 99%

Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory functions

Shao

et al. 2020

Pharmacology & Therapeutics

162

129

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Section: Dpp4/cd26 Inhibition On Infectious Diseasesmentioning

confidence: 99%

Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory functions

Shao

et al. 2020

Pharmacology & Therapeutics

162

129

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“…Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recommended for patients with type 2 diabetes to control glycemia and reduce cardiovascular risk, and for patients with obesity to reduce weight . Given the widespread use of these drugs, potential safety concerns deserve attention.…”

Section: Introductionmentioning

confidence: 99%

Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases

et al. 2022

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IMPORTANCE Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been widely recommended for glucose control and cardiovascular risk reduction in patients with type 2 diabetes, and more recently, for weight loss. However, the associations of GLP-1 RAs with gallbladder or biliary diseases are controversial.OBJECTIVE To evaluate the association of GLP-1 RA treatment with gallbladder and biliary diseases and to explore risk factors for these associations.DATA SOURCES MEDLINE/PubMed, EMBASE, Web of Science, and Cochrane Library (inception to June 30, 2021), websites of clinical trial registries (July 10, 2021), and reference lists. There were no language restrictions. STUDY SELECTION Randomized clinical trials (RCTs) comparing the use of GLP-1 RA drugs with placebo or with non−GLP-1 RA drugs in adults.DATA EXTRACTION AND SYNTHESIS Two reviewers independently extracted data according to the PRISMA recommendations and assessed the quality of each study with the Cochrane Collaboration risk-of-bias tool. Pooled relative risks (RRs) were calculated using random or fixed-effects models, as appropriate. The quality of evidence for each outcome was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. MAIN OUTCOMES AND MEASURESThe primary outcome was the composite of gallbladder or biliary diseases. Secondary outcomes were biliary diseases, biliary cancer, cholecystectomy, cholecystitis, and cholelithiasis. Data analyses were performed from August 5, 2021, to September 3, 2021.RESULTS A total of 76 RCTs involving 103 371 patients (mean [SD] age, 57.8 (6.2) years; 41 868 [40.5%] women) were included. Among all included trials, randomization to GLP-1 RA treatment was associated with increased risks of gallbladder or biliary diseases (RR, 1.37; 95% CI, 1.23-1.52); specifically, cholelithiasis (RR, 1.27; 95% CI, 1.10-1.47), cholecystitis (RR, 1.36; 95% CI, 1.14-1.62), and biliary disease (RR, 1.55; 95% CI, 1.08-2.22). Use of GLP-1 RAs was also associated with increased risk of gallbladder or biliary diseases in trials for weight loss (n = 13; RR, 2.29; 95% CI, 1.64-3.18) and for type 2 diabetes or other diseases (n = 63; RR, 1.27; 95% CI, 1.14-1.43; P <.001 for interaction). Among all included trials, GLP-1 RA use was associated with higher risks of gallbladder or biliary diseases at higher doses (RR, 1.56; 95% CI, 1.36-1.78) compared with lower doses (RR, 0.99; 95% CI, 0.73-1.33; P = .006 for interaction) and with longer duration of use (RR, 1.40; 95% CI, 1.26-1.56) compared with shorter duration (RR, 0.79; 95% CI, 0.48-1.31; P = .03 for interaction).CONCLUSIONS AND RELEVANCE This systematic review and meta-analysis of RCTs found that use of GLP-1 RAs was associated with increased risk of gallbladder or biliary diseases, especially when used at higher doses, for longer durations, and for weight loss.

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“…Metformin is currently the first-line therapy in type 2 diabetes. Some have debated SGLT2i being first-line agents [ 46 ]. SGLT2i can be uptitrated after 4 to 12 weeks to reach glycemic target.…”

Section: Initiating Sglt2 Inhibitors For Diabetes Cardiovascular Dise...mentioning

confidence: 99%

SGLT2 Inhibitors: The Next Blockbuster Multifaceted Drug?

Chan

2023

Medicina

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Sodium glucose cotransporter 2 inhibitor (SGLT2i) is a class of drugs that were originally intended for decreasing blood glucose in diabetes. However, recent trials have shown that there are other beneficial effects. Major clinical trials involving SGLT2i medications from 2015 to 2022 were reviewed using PUBMED search. Recent major SGLT2i landmark trials have demonstrated benefits for cardiovascular disease (reduce major adverse cardiovascular events (heart attack, stroke, cardiovascular death), hospitalization for heart failure, all-cause death), and renal disease (delay the onset of dialysis) regardless of diabetic status. The consistent cardiorenal benefits observed in major landmark trials have resulted in the rapid adoption of SGLT2i therapy not only in diabetes guidelines but also cardiovascular and renal guidelines.

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Compelling evidence for SGLT2 inhibitors and GLP-1 receptor agonists as first-line therapy in patients with diabetes at very high/high cardiovascular risk

Cited by 12 publications

References 6 publications

Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory functions

Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory functions

Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases

SGLT2 Inhibitors: The Next Blockbuster Multifaceted Drug?

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