Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Acta Diabetologica
Published in: Acta Diabetologica 9/2019

01-09-2019 | Albiglutide | Original Article

Effects of exenatide long-acting release on cardiovascular events and mortality in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials

Authors: B. M. Bonora, A. Avogaro, G. P. Fadini

Published in: Acta Diabetologica | Issue 9/2019

Login to get access

Abstract

Aims

Patients with type 2 diabetes (T2D) have an increased risk of cardiovascular disease. Recent cardiovascular outcome trials (CVOTs) with liraglutide, semaglutide, and albiglutide have shown significant reduction in major adverse cardiovascular events. Conversely, the CVOT with exenatide long-acting release (ELAR) confirmed cardiovascular safety of the drug, but did not reached superiority versus placebo. Herein, we systematically evaluated the effect of ELAR versus placebo or active comparators on cardiovascular events and mortality in patients with T2D.

Methods

We screened the literature for randomized controlled trials reporting cardiovascular events and deaths in patients receiving ELAR versus those receiving placebo or any other glucose-lowering medications. Event rates were pooled and compared using the random-effects model.

Result

We retrieved 16 trials comparing the occurrence of cardiovascular events and mortality in patients treated with ELAR versus placebo or active comparators. The pooled rate ratio for cardiovascular events was similar in the two groups (0.99; 95% CI 0.92–1.06). The rate ratio for all-cause mortality was significantly lower in exenatide group than in comparators (0.87; 95% CI 0.77–0.97). When results of the EXSCEL trial were omitted, the pooled rate ratio for cardiovascular events and mortality was 0.80 (95% CI 0.40–1.63) and 0.75 (95% CI 0.30–1.84), respectively.

Conclusions

Treatment with ELAR does not increase the risk of cardiovascular events and may reduce all-cause mortality.
Appendix
Available only for authorised users
Literature
1.
Sarwar N, Gao P, Kondapally Seshasai SR et al (2010) Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 375(9733):2215–2222CrossRef
2.
Kondapally Seshasai SR, Kaptoge S, Thompson A et al (2011) Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med. 364(9):829–841CrossRef
3.
Zoungas S, Arima H, Gerstein HC et al (2017) Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual participant data from randomised controlled trials. Lancet Diabetes Endocrinol 5(6):431–437CrossRef
4.
Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HAW (2008) 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 359(15):1577–1589CrossRef
5.
Uni- M, Sciences HH, Miller ME et al (2011) Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med 364(9):818–828CrossRef
6.
Nissen SE, Wolski K (2007) Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 356(24):2457–2471CrossRef
7.
Petrie JR (2013) The cardiovascular safety of incretin-based therapies: a review of the evidence. Cardiovasc Diabetol 12(1):130CrossRef
8.
Pfeffer MA, Claggett B, Diaz R et al (2015) Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med 373(23):2247–2257CrossRef
9.
Jones B (2016) Liraglutide and cardiovascular outcomes in type 2 diabetes. Ann Clin Biochem 53(6):712CrossRef
10.
Marso SP, Bain SC, Consoli A et al (2016) Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 375(19):1834–1844CrossRef
11.
Hernandez AF, Green JB, Janmohamed S et al (2018) Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet 392(10157):1519–1529CrossRef
12.
Holman RR, Bethel MA, Mentz RJ et al (2017) Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med 377(13):1228–1239CrossRef
13.
Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the prisma statement. Ann Intern Med. 151(4):264–269CrossRef
14.
Higgins JPT, Altman DG, Gøtzsche PC et al (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 18(343):d5928CrossRef
15.
Kunz LM, Normand S-LT, Sedrakyan A (2015) Meta-analysis of rate ratios with differential follow-up by treatment arm: inferring comparative effectiveness of medical devices. Stat Med 34(21):2913–2925CrossRef
16.
Newman JD, Vani AK, Aleman JO, Weintraub HS, Berger JS, Schwartzbard AZ (2018) The changing landscape of diabetes therapy for cardiovascular risk reduction: JACC state-of-the-art review. J Am Coll Cardiol 72(15):1856–1869CrossRef
17.
Hernandez AF, Green JB, Janmohamed S et al (2018) Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet. 392(10157):1519–1529CrossRef
18.
Walter SD (1991) Statistical significance and fragility criteria for assessing a difference of two proportions. J Clin Epidemiol. 44(12):1373–1378CrossRef
19.
Meier JJ (2012) GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 8:728CrossRef
20.
Lund A, Knop FK, Vilsbøll T (2014) Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes: differences and similarities. Eur J Intern Med 25(5):407–414CrossRef
21.
Gerstein HC, Colhoun HM, Dagenais GR et al (2018) Design and baseline characteristics of participants in the Researching cardiovascular events with a weekly incretin in diabetes (REWIND) trial on the cardiovascular effects of dulaglutide. Diabetes Obes Metab 20(1):42–49CrossRef
22.
Bain SC, Mosenzon O, Arechavaleta R et al (2018) Cardiovascular safety of oral semaglutide in patients with type 2 diabetes: rationale, design and patient baseline characteristics for the PIONEER 6 trial. Diabetes Obes Metab 21(3):499–508CrossRef
23.
24.
25.
26.
Buse JB, Nauck M, Forst T et al (2013) Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study. Lancet 381(9861):117–124CrossRef
27.
Jabbour SA, Frías JP, Hardy E et al (2018) Safety and efficacy of exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy: 52-week results of the DURATION-8 randomized controlled. Diabetes Care 41(10):2136–2146CrossRef
28.
Ahmann AJ, Capehorn M, Charpentier G et al (2018) Efficacy and safety of once-weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3): a 56-week, open-label, randomized clinical trial. Diabetes Care 41(2):258–266CrossRef
29.
Drucker DJ, Buse JB, Taylor K et al (2008) Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet 372(9645):1240–1250CrossRef
30.
Bergenstal RM, Wysham C, MacConell L et al (2010) Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet 376(9739):431–439CrossRef
31.
Diamant M, Van Gaal L, Stranks S et al (2010) Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial. Lancet 375(9733):2234–2243CrossRef
32.
Russell-Jones D, Cuddihy RM, Hanefeld M et al (2012) Efficacy and safety of exenatide once weekly versus metformin, pioglitazone, and sitagliptin used as monotherapy in drug-naive patients with type 2 diabetes (DURATION-4). Diabetes Care 35(2):252–258CrossRef
33.
Blevins T, Pullman J, Malloy J et al (2011) DURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endocrinol Metab 96(5):1301–1310CrossRef
34.
Guja C, Frías JP, Somogyi A et al (2018) Effect of exenatide QW or placebo, both added to titrated insulin glargine, in uncontrolled type 2 diabetes: the DURATION-7 randomized study. Diabetes Obes Metab 20:1602–1614CrossRef
35.
Wysham CH, Rosenstock J, Vetter ML (2018) Efficacy and tolerability of the new autoinjected suspension of exenatide once weekly versus exenatide twice daily in patients with type 2 diabetes. Diabetes Obes Metab 20(1):165–172CrossRef
36.
Gadde KM, Vetter ML, Iqbal N, Hardy E, Öhman P (2017) Efficacy and safety of autoinjected exenatide once-weekly suspension versus sitagliptin or placebo with metformin in patients with type 2 diabetes: the DURATION-NEO-2 randomized clinical study. Diabetes Obes Metab 19(7):979–988CrossRef
37.
Davies M, Heller S, Sreenan S et al (2013) Once-weekly exenatide versus once- or twice-daily insulin detemir, (5 CC-Metabolic and Endocrine Disorders). Diabetes Care. 36:1368–1376CrossRef
38.
Inagaki N, Atsumi Y, Oura T, Saito H, Imaoka T (2012) Efficacy and safety profile of exenatide once weekly compared with insulin once daily in japanese patients with type 2 diabetes treated with oral antidiabetes drug(s): results from a 26-week, randomized, open-label, parallel-group, multicenter. Noninferio Clin Ther. 34(9):1892–1908.e1CrossRef
39.
Ji L, Onishi Y, Ahn CW et al (2013) Efficacy and safety of exenatide once-weekly vs exenatide twice-daily in Asian patients with type 2 diabetes mellitus. J Diabetes Investig 4(1):53–61CrossRef
40.
Abdul-Ghani M, Migahid O, Megahed A, Adams J, Triplitt C, DeFronzo RA et al (2017) Combination therapy with exenatide plus pioglitazone versus basal/bolus insulin in patients with poorly controlled type 2 diabetes on sulfonylurea plus metformin: the qatar study. Diabetes Care 40(3):325–331CrossRef
Metadata
Title
Effects of exenatide long-acting release on cardiovascular events and mortality in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials
Authors
B. M. Bonora
A. Avogaro
G. P. Fadini
Publication date
01-09-2019
Publisher
Springer Milan
Published in
Acta Diabetologica / Issue 9/2019
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-019-01347-0

Other articles of this Issue 9/2019

Acta Diabetologica 9/2019 Go to the issue

Original Article

Association between resting heart rate and incident diabetes risk: a Mendelian randomization study

Original Article

Transgenerational cycle of obesity and diabetes: investigating possible metabolic precursors in cord blood from the PREOBE study

Original Article

Pharmacological blockade of the P2X7 receptor reverses retinal damage in a rat model of type 1 diabetes

Letter to the Editor

Reply to Josef Finsterer “MELAS requires broad clinical and genetic work-up”

Original Article

Lung function measurements in the prediabetes stage: data from the ILERVAS Project

Original Article

Different treatment forms of type II diabetes and the risk of dementia in German health claims data

ACC 2024 Congress Coverage

Cardiology Video

Highlights from the ACC 2024 Congress

Watch now

Watch official videos from the ACC congress summarizing key highlights from the last year in heart failure, cardiomyopathies, valvular disease, pulmonary vascular disease, and pediatric cardiology.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits