TY - JOUR
T1 - The Longer-Term Benefits and Harms of Glucagon-Like Peptide-1 Receptor Agonists
T2 - a Systematic Review and Meta-Analysis
AU - Alexander, Jason T.
AU - Staab, Erin M.
AU - Wan, Wen
AU - Franco, Melissa
AU - Knitter, Alexandra
AU - Skandari, M. Reza
AU - Bolen, Shari
AU - Maruthur, Nisa M.
AU - Huang, Elbert S.
AU - Philipson, Louis H.
AU - Winn, Aaron N.
AU - Thomas, Celeste C.
AU - Zeytinoglu, Meltem
AU - Press, Valerie G.
AU - Tung, Elizabeth L.
AU - Gunter, Kathryn
AU - Bindon, Brittany
AU - Jumani, Sanjay
AU - Laiteerapong, Neda
N1 - Publisher Copyright:
© 2021, Society of General Internal Medicine.
PY - 2022/2
Y1 - 2022/2
N2 - Background: Previous meta-analyses of the benefits and harms of glucagon-like peptide-1 receptor agonists (GLP1RAs) have been limited to specific outcomes and comparisons and often included short-term results. We aimed to estimate the longer-term effects of GLP1RAs on cardiovascular risk factors, microvascular and macrovascular complications, mortality, and adverse events in patients with type 2 diabetes, compared to placebo and other anti-hyperglycemic medications. Methods: We searched PubMed, Scopus, and clinicaltrials.gov (inception–July 2019) for randomized controlled trials ≥ 52 weeks’ duration that compared a GLP1RA to placebo or other anti-hyperglycemic medication and included at least one outcome of interest. Outcomes included cardiovascular risk factors, microvascular and macrovascular complications, all-cause mortality, and treatment-related adverse events. We performed random effects meta-analyses to give summary estimates using weighted mean differences (MD) and pooled relative risks (RR). Risk of bias was assessed using the Cochrane Collaboration risk of bias in randomized trials tool. Quality of evidence was summarized using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The study was registered a priori with PROSPERO (CRD42018090506). Results: Forty-five trials with a mean duration of 1.7 years comprising 71,517 patients were included. Compared to placebo, GLP1RAs reduced cardiovascular risk factors, microvascular complications (including renal events, RR 0.85, 0.80–0.90), macrovascular complications (including stroke, RR 0.86, 0.78–0.95), and mortality (RR 0.89, 0.84–0.94). Compared to other anti-hyperglycemic medications, GLP1RAs only reduced cardiovascular risk factors. Increased gastrointestinal events causing treatment discontinuation were observed in both comparisons. Discussion: GLP1RAs reduced cardiovascular risk factors and increased gastrointestinal events compared to placebo and other anti-hyperglycemic medications. GLP1RAs also reduced MACE, stroke, renal events, and mortality in comparisons with placebo; however, analyses were inconclusive for comparisons with other anti-hyperglycemic medications. Given the high costs of GLP1RAs, the lack of long-term evidence comparing GLP1RAs to other anti-hyperglycemic medications has significant policy and clinical practice implications.
AB - Background: Previous meta-analyses of the benefits and harms of glucagon-like peptide-1 receptor agonists (GLP1RAs) have been limited to specific outcomes and comparisons and often included short-term results. We aimed to estimate the longer-term effects of GLP1RAs on cardiovascular risk factors, microvascular and macrovascular complications, mortality, and adverse events in patients with type 2 diabetes, compared to placebo and other anti-hyperglycemic medications. Methods: We searched PubMed, Scopus, and clinicaltrials.gov (inception–July 2019) for randomized controlled trials ≥ 52 weeks’ duration that compared a GLP1RA to placebo or other anti-hyperglycemic medication and included at least one outcome of interest. Outcomes included cardiovascular risk factors, microvascular and macrovascular complications, all-cause mortality, and treatment-related adverse events. We performed random effects meta-analyses to give summary estimates using weighted mean differences (MD) and pooled relative risks (RR). Risk of bias was assessed using the Cochrane Collaboration risk of bias in randomized trials tool. Quality of evidence was summarized using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The study was registered a priori with PROSPERO (CRD42018090506). Results: Forty-five trials with a mean duration of 1.7 years comprising 71,517 patients were included. Compared to placebo, GLP1RAs reduced cardiovascular risk factors, microvascular complications (including renal events, RR 0.85, 0.80–0.90), macrovascular complications (including stroke, RR 0.86, 0.78–0.95), and mortality (RR 0.89, 0.84–0.94). Compared to other anti-hyperglycemic medications, GLP1RAs only reduced cardiovascular risk factors. Increased gastrointestinal events causing treatment discontinuation were observed in both comparisons. Discussion: GLP1RAs reduced cardiovascular risk factors and increased gastrointestinal events compared to placebo and other anti-hyperglycemic medications. GLP1RAs also reduced MACE, stroke, renal events, and mortality in comparisons with placebo; however, analyses were inconclusive for comparisons with other anti-hyperglycemic medications. Given the high costs of GLP1RAs, the lack of long-term evidence comparing GLP1RAs to other anti-hyperglycemic medications has significant policy and clinical practice implications.
KW - diabetes
KW - glucagon-like peptide-1 receptor agonists
KW - meta-analysis
KW - systematic review
UR - http://www.scopus.com/inward/record.url?scp=85114689131&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85114689131&partnerID=8YFLogxK
U2 - 10.1007/s11606-021-07105-9
DO - 10.1007/s11606-021-07105-9
M3 - Review article
C2 - 34508290
AN - SCOPUS:85114689131
SN - 0884-8734
VL - 37
SP - 415
EP - 438
JO - Journal of general internal medicine
JF - Journal of general internal medicine
IS - 2
ER -