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05-28-2018 | Sulfonylureas | Article

Meta-Analysis of Sulfonylurea Therapy on Long-Term Risk of Mortality and Cardiovascular Events Compared to Other Oral Glucose-Lowering Treatments

Journal: Diabetes Therapy

Authors: W. Ryan Powell, Cindy L. Christiansen, Donald R. Miller

Publisher: Springer Healthcare

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Abstract

Introduction

Among the most pressing clinical decisions in type 2 diabetes treatments are which drugs should be used after metformin is no longer sufficient, and whether sulfonylureas (SUs) should remain as a suitable second-line treatment. In this article we summarize current evidence on the long-term safety risks associated with SU therapy relative to other oral glucose-lowering therapies.

Methods

The MEDLINE database and Clinicaltrials.gov were searched for observational and experimental studies comparing the safety of SUs to that of other diabetes medications in people with type 2 diabetes mellitus through December 15, 2015. Studies with at least 1 year of follow-up, which explicitly examined major cardiovascular events or death in patients who showed no evidence of serious conditions at baseline, were selected for inclusion in meta-analyses.

Results

SU treatment was associated with an elevated risk relative to treatment with metformin (METF), thiazolidinedione (TZD), dipeptidyl peptidase-4 inhibitor (DPP-4), and glucagon-like peptide-1 (GLP-1) agonist classes, either when compared alone (as a monotherapy) or when used in combination with METF. Significant findings were almost entirely derived from nontrial data and not confirmed by smaller, efficacy designed randomized controlled trials whose effects were in the same direction but much more imprecise.

Conclusion

Although much of the evidence is derived and will continue to come from observational studies, the methodological rigor of such studies is questionable. A key challenge for evaluators is the extent to which they should incorporate evidence from study designs that are quasi-experimental.
Literature
1.
Bolen S, Tseng E, Hutfless S, et al. Diabetes medications for adults with Type 2 diabetes: an update. Rockville: Agency for Healthcare Research and Quality (US); 2016.
2.
United Kingdom Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352(9131):837–853.
3.
Abrahamson MJ. Should sulfonylureas remain an acceptable first-line add-on to metformin therapy in patients with type 2 diabetes? Yes, they continue to serve us well! Diabetes Care. 2015;38(1):166–9. CrossRefPubMed
4.
Genuth S. Should sulfonylureas remain an acceptable first-line add-on to metformin therapy in patients with type 2 diabetes? No, it’s time to move on! Diabetes Care. 2015;38(1):170–5. CrossRefPubMed
5.
Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12. CrossRefPubMed
6.
Wells G, Shea B, O’Connell D, et al. The Newcastle–Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in metaanalyses [Internet]; 2001. http://​www.​medicine.​mcgill.​ca/​rtamblyn/​Readings%5CThe%20​Newcastle%20​-%20​Scale%20​for%20​assessing%20​the%20​quality%20​of%20​nonrandomised%20​studies%20​in%20​meta-analyses.​pdf.
7.
Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. Introduction to meta-analysis. Chichester: Wiley; 2009. CrossRef
8.
StataCorp LP. Stata statistical software: release 14. College Station: StataCorp LP; 2015.
9.
Peters JL, Rushton L, Sutton AJ, Jones DR, Abrams KR, Mugglestone MA. Bayesian methods for the cross-design synthesis of epidemiological and toxicological evidence. J R Stat Soc Ser C Appl Stat. 2005;54(1):159–72. CrossRef
10.
Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60. CrossRefPubMedPubMedCentral
11.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34. CrossRefPubMedPubMedCentral
12.
Harbord RM, Harris RJ, Sterne JAC. Updated tests for small-study effects in meta-analyses. Stata J. 2009;9(2):197–210.
13.
Higgins, JPT, Green S. Cochrane handbook for systematic reviews of interventions (5.1.0 [updated March 2011]). Hoboken: John Wiley & Sons. http://​www.​handbook.​cochrane.​org.
14.
Gribble FM, Tucker SJ, Seino S, Ashcroft FM. Tissue specificity of sulfonylureas: studies on cloned cardiac and β-cell K(ATP) channels. Diabetes. 1998;47:1412–8. CrossRefPubMed
15.
Scirica BM, Braunwald E, Raz I, et al. Heart failure, saxagliptin and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation 2014;130(18):1579–88.
16.
Regier EE, Venkat MV, Close KL. More than 7 years of hindsight: revisiting the FDA’s 2008 guidance on cardiovascular outcomes trials for Type 2 diabetes medications. Clin Diabetes. 2016;34(4):173–80. CrossRefPubMedPubMedCentral
17.
Vaccaro O, Masulli M, Nicolucci A, et al. Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial. Lancet Diabetes Endocrinol. 2017;5(11):887–97. CrossRefPubMed
18.
Nathan DM, Buse JB, Kahn SE, et al. Rationale and design of the glycemia reduction approaches in diabetes: a comparative effectiveness study (GRADE). Diabetes Care. 2013;36(8):2254–61. CrossRefPubMedPubMedCentral
19.
Marx N, Rosenstock J, Kahn SE, et al. Design and baseline characteristics of the CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes (CAROLINA®). Diab Vasc Dis Res. 2015;12(3):164–174.
20.
114th U.S. Congress. 21st Century Cures Act; H.R. 34 (114-255 Public Law 114–255); 2015.
21.
Goodman SN. Bayesian methods for evidence evaluation. Circulation. 2013;127(24):2367–9. CrossRefPubMed