EASD 2020 Highlights

Conference summaries


Effects of tirzepatide, a novel dual GIP and GLP-1 receptor agonist, on metabolic profile in patients with type 2 diabetes

Presented by:

Valentina Pirro, MD

  • Tirzepatide significantly affects levels of BCAAs, as well as 2-hydroxybutyric acid, a marker of dysregulated metabolism.
  • Changes in BCAAs correlated with changes in insulin sensitivity.
  • The differences in BCAAs after tirzepatide are more marked than those seen with dulaglutide.

What do we already know about this topic?

  • Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that is being developed for the treatment of type 2 diabetes (T2D).1
  • Tirzepatide has been studied in a double-blind, randomised, phase 2 study in which patients with T2D were assigned (1:1:1:1:1:1) to receive either once-weekly subcutaneous tirzepatide (1 mg, 5 mg, 10 mg, or 15 mg), dulaglutide (1.5 mg), or placebo for 26 weeks.1
  • Tirzepatide showed significantly better efficacy in terms of glucose control and weight loss than did dulaglutide, with an acceptable safety and tolerability profile.1

How was this study conducted?

  • This analysis examined the metabolic profile of 259 patients from that cohort.
  • Plasma samples were analysed using a targeted mass spectrometry metabolomics approach.

What does this study add?

  • Branched chain amino acids (BCAAs) and catabolic products were strongly associated with markers of improved insulin sensitivity.
  • BCAAs and 2-hydroxybutyric acid were strongly associated with improved HbA1c.
  • Circulating levels of BCAAs and related metabolites are modulated in a dose-dependent manner following treatment with tirzepatide.
  • The metabolic changes after tirzepatide treatment exceed those of dulaglutide.
  • Changes in BCAAs correlated with changes in HOMA2-IR and HbA1c levels, but not with weight loss.


How does this study impact clinical practice?

  • These results further support existing evidence that dysregulated BCAA metabolism is both a marker for and a potential causal agent for both insulin resistance and glucose tolerance.2
  • Tirzepatide significantly modulates circulating levels of BCAAs and products of their catabolism, as well as 2-hydroxybutyric acid, an independent marker of dysregulated metabolism
  • Modulation of BCAAs has a strong correlation with changes in insulin sensitivity, but not weight loss
  • The metabolic changes following tirzepatide treatment are more marked than those seen with dulaglutide, and consistent with its greater impact on insulin sensitivity and glucose control.



  1. Frias JP, Nauck MA, Van J, et al. Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial. Lancet. 2018 Nov 17;392(10160):2180-93.
  2. White PJ, Newgard CB. Branched-chain amino acids in disease. Science. 2019 Feb 8;363(6427):582-3.


Related content


This is a highlights summary of an oral session given at the EASD 2020 Virtual Meeting and presented by:

Valentina Pirro, MD
Eli Lilly, Indianapolis, IN, USA

The presenting authors of the original session had no part in the creation of this conference highlights summary. 

The content is produced by Infomedica. The summary text was drafted by Patrick Moore, PhD, and reviewed by Marco Gallo, MD, an independent external expert, and approved by Florian Toti, MD, the scientific editor of the program.


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