Challenging Clinical Perspectives in Type 2 Diabetes with Tirzepatide, a First-in-Class Twincretin

Richard J MacIsaac; Gary Deed; Michael D'Emden; Elif I Ekinci; Samantha Hocking; Priya Sumithran; Roy Rasalam

doi:10.1007/s13300-023-01475-5

Challenging Clinical Perspectives in Type 2 Diabetes with Tirzepatide, a First-in-Class Twincretin

Diabetes Ther. 2023 Dec;14(12):1997-2014. doi: 10.1007/s13300-023-01475-5. Epub 2023 Oct 12.

Authors

Richard J MacIsaac^{1

2

3

4}, Gary Deed⁵, Michael D'Emden^{6

7}, Elif I Ekinci^{8

9

10}, Samantha Hocking^{11

12}, Priya Sumithran^{13

14

15}, Roy Rasalam^{16

17}

Affiliations

¹ Department of Endocrinology and Diabetes, St Vincent's Hospital Melbourne, Fitzroy, VIC, Australia. r.macisaac@unimelb.edu.au.
² The Australian Centre for Accelerating Diabetes Innovations, Melbourne Medical School, The University of Melbourne, Parkville, VIC, Australia. r.macisaac@unimelb.edu.au.
³ Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, VIC, Australia. r.macisaac@unimelb.edu.au.
⁴ Department of Endocrinology and Diabetes, Level 4 Daly Wing, 35 Victoria Pde, PO Box 2900, Fitzroy, VIC, 3065, Australia. r.macisaac@unimelb.edu.au.
⁵ Monash University, Brisbane, QLD, Australia.
⁶ Department of Endocrinology and Diabetes, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.
⁷ Queensland Health, Brisbane, QLD, Australia.
⁸ The Australian Centre for Accelerating Diabetes Innovations, Melbourne Medical School, The University of Melbourne, Parkville, VIC, Australia.
⁹ Department of Endocrinology, Austin Health, Heidelberg, VIC, Australia.
¹⁰ Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia.
¹¹ Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
¹² Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
¹³ Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, VIC, Australia.
¹⁴ Central Clinical School, Monash University, Melbourne, VIC, Australia.
¹⁵ Department of Endocrinology and Diabetes, Alfred Health, Melbourne, VIC, Australia.
¹⁶ Department of Endocrinology and Diabetes, Alfred Health, Melbourne, VIC, Australia. roy.rasalam@unimelb.edu.au.
¹⁷ University of Melbourne, Parkville, VIC, 3010, Australia. roy.rasalam@unimelb.edu.au.

Abstract

Tirzepatide is a first-in-class GIP/GLP-1 receptor agonist ('twincretin')-a single molecule that acts as an agonist at both glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. In the SURPASS clinical trial program in type 2 diabetes mellitus (T2D), tirzepatide was associated with unprecedented reductions in HbA1c, clinically significant weight loss and other metabolic benefits, combined with low rates of hypoglycaemia across a wide range of patient characteristics. The safety and adverse event rate for tirzepatide appears comparable to that of GLP-1 receptor agonists. Although results from dedicated cardiovascular (CV) and kidney trials are currently not available, information to date suggests that tirzepatide may have CV and kidney benefits in people with T2D. Tirzepatide has been approved for the treatment of T2D in the USA, United Arab Emirates, European Union, Japan and Australia. Here, we review how tirzepatide will fit into the T2D treatment continuum. We also consider future directions with tirzepatide in T2D, including its potential for targeting cardio-renal-metabolic disease in T2D, and discuss how tirzepatide-and other co-agonists in development-may challenge current approaches for management of T2D.

Keywords: Body weight/drug therapy; Cardio-renal-metabolic disease; GIP/GLP-1 receptor agonist; SURPASS clinical trials; Tirzepatide; Twincretin; Type 2 diabetes/drug therapy.

Publication types

Review