Translation of a-t 2024; 55: 56

Decreased thirst sensation with tirzepatide (MOUNJARO)

A 51-year-old female and a 46-year-old male subcutaneously injected up to 5 mg and 10 mg of the GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptor agonist tirzepatide (MOUNJARO), respectively, once a week to trigger weight loss. Shortly after starting treatment and after using the product for approximately three months, respectively, they noticed a substantial decrease in or even lack of thirst sensation during or after sport in particular (NETZWERK reports 18.474 and 18.475). Neither the current German Summary of Product Characteristics¹ (SPC) nor the US Product Information^2,3 contains any evidence of this type of adverse effect with this medicinal product, which has been approved in Germany for type 2 diabetes mellitus and obesity (a-t 2023; 54: 91-2 and 2024; 55: 29-30). Similarly, we find no published reports of decreased thirst sensation with tirzepatide. However, a reduction in thirst sensation and fluid consumption has long since been associated with the GLP-1 hormone in animal studies and in humans.^{e.g. 4,5} There is also evidence of corresponding effects with pure GLP-1 agonists used as medicinal products: In two laboratory studies, overall water consumption was reduced in rats following intraperitoneal and intraventricular or exclusively intraventricular injection of liraglutide (VICTOZA, SAXENDA; a-t 2009; 40: 80-2 and 2016; 47: 47-8) and exendin-4 (equivalent to exenatide [BYDUREON, BYETTA]; a-t 2007; 38: 43-5) over 24-hour and 2-hour observation periods, respectively, compared to that recorded following injection of physiological saline solution.^6,7 This was apparently regardless of reduced feed intake during administration of the active substances.⁶ In two small, randomised, double-blind, crossover studies conducted by a Swiss working group and involving 20 healthy volunteers⁸ and 35 patients with primary polydipsia,⁹ participants receiving 1.5 mg of the pure GLP-1 agonist dulaglutide s.c. once a week for three weeks (TRULICITY; a-t 2015; 46: 27-8) drank smaller quantities or significantly less during an 8-hour test with standardised meals compared to those receiving placebo (median 1,300 ml versus 1,600 ml and, on average, 2,460 ml versus 2,950 ml, respectively).^8,9 Decreased thirst sensation was also reported with the active drug substance in the larger-scale study.⁹ The authors refer to a laboratory test demonstrating marked neuron expression of GLP-1 receptors in the murine brain, which are supposed to suppress thirst as soon as fluid is consumed, although the intracerebral injection of exendin-4 (exenatide) did not affect the drinking volume of the animals in this study.¹⁰ It seems plausible to us that tirzepatide could also decrease the thirst sensation. If decreased thirst sensation is observed during treatment with tirzepatide or also with pure GLP-1 agonists, please report this to our NETZWERK DER GEGENSEITIGEN INFORMATION.

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