Tirzepatide Improves Metabolic and Lipid Profiles in Type 2 Diabetes

Lipid Profile test
Test tube with blood for Lipid Profile test.
Type 2 diabetes interferes with the body’s regulation of insulin, glucose, lipids, and amino acids. Results of a phase 2b clinical trial combining glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were studied for their effectiveness in type 2 diabetes.

Metabolic and lipid health profiles were found to improve with tirzepatide therapy among patients with type 2 diabetes (T2D). These findings, from a post hoc analysis of data from a phase 2b trial, were published in The Journal of Clinical Endocrinology and Metabolism.

Trial participants (N=316) were equally randomized into 6 treatment groups: weekly subcutaneous injection with 1, 5, 10, or 15 mg tirzepatide; 1.5 mg dulaglutide; or placebo for 26 weeks. Metabolic and lipid profiles were assessed.

At week 26, doses of 1, 5, 10, and 15 mg tirzepatide associated with significant changes from baseline for 3, 33, 35, and 54 metabolites, respectively. In response to dulaglutide, 6 metabolites changed from baseline and no change was observed among placebo recipients.

The altered metabolites were correlated for 15 mg with 10 mg (r, 0.92; P <.0001) and 5 mg (r, 0.89; P <.0001) doses.

The altered metabolites in the highest dose cohort were observed to associate with circulating intact proinsulin levels, glycated hemoglobin (HbA1c), and homeostatic model assessment for insulin resistance (HOMA) 2-IR but not with weight loss.

Among the 10 and 15 mg dose recipients, diglycerides, triglycerides, and phosphatidylethanolamines were significantly decreased.

Similar to the altered metabolites, the decreased triglycerides among the highest-dose group associated with circulating intact proinsulin levels (r, 0.60; P <.001), HbA1C (r, 0.62; P <.001), and HOMA2-IR indices (r, 0.41; P <.05). There was a direct relationship between triglyceride changes with weight loss among the dulaglutide recipients but not among the tirzepatide recipients despite the fact that weight loss was greater among the highest dose tirzepatide recipients (mean, -11.3 kg vs -2.7).

Although the changes in metabolites and lipids were not associated with weight loss directly, the cluster of metabolites and lipids were associated in previous reports with obesity as well as insulin resistance and future T2D risk.

This study was likely limited by the dose of the comparator dulaglutide, however, at the time of the study, 1.5 mg was the highest approved dosage. Currently, doses of up to 4.5 mg are approved.

The study authors concluded that, in addition to weight loss, this post-hoc analysis of trial data indicated that high-dose tirzepatide was associated with the most favorable changes to metabolites and lipid profiles linked to T2D risk.

Disclosure: The study was funded by Eli Lilly and Company, manufacturers of tirzepatide, and multiple authors declared affiliations or employment with the company. Please refer to the original article for a full list of disclosures.


Pirro V, Roth KD, Lin Y, et al. Effects of tirzepatide, a dual GIP and GLP-1 RA, on lipid and metabolite profiles in subjects with type 2 diabetes. J Clin Endocrinol Metab. Published online October 5, 2021. doi:10.1210/clinem/dgab722