GLP-1 receptor agonists: differentiation within the class - PubMed (original) (raw)

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GLP-1 receptor agonists: differentiation within the class

Simeon I Taylor. Lancet Diabetes Endocrinol. 2018 Feb.

No abstract available

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Figure. Magnitude of cardioprotection is correlated with HbA1c-lowering

Hazard ratios from SUSTAIN-6, LEADER, EXSCEL, and ELIXA– are plotted on the vertical axis as a function of ‘normalized’ HbA1c-lowering plotted on the horizontal axis. To account for variation in study design among six head-to-head efficacy studies–, HbA1c-lowering data were normalized as follows:

1. Normalized HbA1c-lowering for short-acting exenatide/BYETTA was defined as 1.00%.
2. Normalized HbA1c-lowering for lixisenatide was calculated based on head-to-head comparative efficacy data obtained in the GetGoal-X study. Observed HbA1c-lowering was 0.96% for short-acting exenatide/BYETTA and 0.79% for lixisenatide, corresponding to an Efficacy Ratio of 0.82 (=0.79% / 0.96%). A normalized HbA1c-lowering for lixisenatide of **0.82%**was calculated by multiplying the Efficacy Ratio (0.82) times the normalized HbA1c-lowering for short-acting exenatide (1.00%).
3. Normalized HbA1c-lowering for long-acting exenatide/BYDUREON was calculated in a similar fashion based on comparative efficacy data in the DURATION-1 study. This yielded a value of1.27% as the normalized HbA1c-lowering for long-acting exenatide [BYETTA].
4. The DURATION-6 and SUSTAIN-3 studies reported Efficacy Ratios of 1.16 and 1.67 for liraglutide and semaglutide, respectively, relative to extended-release exenatide/BYDUREON. These calculations yield values for normalized HbA1c-lowering of 1.47% and 2.12% for liraglutide and semaglutide, respectively.
5. The AWARD-6 and HARMONY-7 studies reported Efficacy Ratios of 1.04 and 0.79 for dulaglutide and albiglutide, respectively, relative to liraglutide. These calculations yield values for normalized HbA1c-lowering of1.53% and 1.16% for dulaglutide and albiglutide, respectively.

Comment in

• GLP-1 receptor agonists and cardiovascular disease: drug-specific or class effects?
  Zweck E, Roden M. Zweck E, et al. Lancet Diabetes Endocrinol. 2019 Feb;7(2):89-90. doi: 10.1016/S2213-8587(18)30351-6. Lancet Diabetes Endocrinol. 2019. PMID: 30683221 No abstract available.

Comment on

• Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis.
  Bethel MA, Patel RA, Merrill P, Lokhnygina Y, Buse JB, Mentz RJ, Pagidipati NJ, Chan JC, Gustavson SM, Iqbal N, Maggioni AP, Öhman P, Poulter NR, Ramachandran A, Zinman B, Hernandez AF, Holman RR; EXSCEL Study Group. Bethel MA, et al. Lancet Diabetes Endocrinol. 2018 Feb;6(2):105-113. doi: 10.1016/S2213-8587(17)30412-6. Epub 2017 Dec 6. Lancet Diabetes Endocrinol. 2018. PMID: 29221659

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