Dual incretin analogue tirzepitide - SURMOUNTing the challenge of obesity induced obstructive sleep apnea

Table 1 Summary of main results from the SURMOUNT-obstructive sleep apnoea trials

Group	Tirzepatide	Placebo	Treatment difference
Mean change in AHI
Trial 1	-25.3 (-29.3 to -21.2)	-5.3 (-9.4 to -1.1)	-20.0 (-25.8 to -14.2)
Trial 2	-29.3 (-33.2 to -25.4)	-5.5 (-9.9 to -1.2)	-23.8 (-29.6 to -17.9)
Change in AHI (%)
Trial 1	-50.7 (-62.3 to -39.1)	-3.0 (-16.9 to 10.9)	-47.7 (-65.8 to -29.6)
Trial 2	-58.7 (-69.1 to -48.4)	-2.5 (-16.2 to 11.2)	-56.2 (-73.7 to -38.7)
Change in body weight (%)
Trial 1	-17.7 (-19.0 to -16.3)	-1.6 (-2.9 to -0.2)	-16.1 (-18.0 to -14.2)
Trial 2	-19.6 (-21.0 to -18.2)	-2.3 (-3.8 to -0.9)	-17.3 (-19.3 to -15.3)
Change in systolic blood pressure
Trial 1	-9.5 (-11.5 to -7.5)	-1.8 (-3.9 to 0.2)	-7.6 (-10.5 to -4.8)
Trial 2	-7.6 (-9.7 to -5.6)	-3.9 (-6.3 to -1.6)	-3.7 (-6.8 to -0.7)
Change in diastolic blood pressure
Trial 1	-4.9 (-6.4 to -3.5)	-2.1 (-3.6 to -0.6)	-2.8 (-5.0 to -0.7)
Trial 2	-3.3 (-4.7 to -1.9)	-2.2 (-3.8 to -0.6)	-1.1 (-3.2 to 1.0)

There were two parts of the study: Trial 1 was done on patients without background continuous positive airway pressure therapy while trial 2 enrolled patients on background continuous positive airway pressure therapy. AHI: Apnoea hypopnea index.

Table 2 Comparison of the two major parenteral incretin analogues - semaglutide and tirzepatide

Parameters	Semaglutide	Tirzepatide
Drug class	GLP-1 receptor agonist	Dual GIP and GLP-1 receptor agonist (twincretin)
Mechanism of action	Mimics GLP-1: Suppresses appetite, slows gastric emptying, regulates insulin and glucagon	Activates both GIP and GLP-1 receptors: Synergistically reduces appetite, enhances insulin sensitivity
Receptor targets	GLP-1 only	GLP-1 and GIP
Dosing frequency	Once weekly (subcutaneous)	Once weekly (subcutaneous)
FDA approval for obesity	Approved (as Wegovy)	Approved for Obesity/OSA (as Zepbound)
Additional benefits	Cardiovascular risk reduction	Potentially better metabolic and cardiovascular profile
Effect on appetite	Reduces appetite via central GLP-1 pathways	Stronger appetite suppression via dual hormone action
Effect on gastric emptying	Slows gastric emptying	Slows gastric emptying
Insulin sensitivity	Improves glucose-dependent insulin secretion	Further improves insulin sensitivity through GIP action
Weight loss efficacy	High (average about 10%-15% body weight reduction)	Higher (average about 15%-22% body weight reduction)

GLP: Glucagon like peeptide; GIP: Glucose dependent insulinotropic polypeptide.