Tirzepatide shown to be effective at reducing sleep disturbances in patients with obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is highly prevalent in patients with obesity with or without type 2 diabetes. Data from the American diabetes Association reported that around 40% of patients with obesity have OSA. Continuous Positive Airway pressure (CPAP) is an effective and the most-used intervention for OSA, but many patients may not be able to tolerate the device or stop using it. Tirzepatide a dual GLP-1 GIP agonist has been shown to induce significant weight loss and improve glycaemic control in people with type 2 diabetes. Whether the weight loss induced by Tirzepatide could positively affect the severity and improve outcome in people with OSA however remains unclear.

To clarify this, SURMOUNT-OSA was undertaken. This was a combination of two phase 3, multi-center, randomized, double-blind, parallel, placebo-master protocol studies, comparing the efficacy and safety of tirzepatide to placebo in adults living with moderate-to-severe obstructive sleep apnea and obesity who were unable or unwilling to use CPAP (Study 1) and those who were and planned to stay on CPAP therapy during the duration of the trial (Study 2). The trials randomized 469 participants from 60 sites across 9 countries, in a 1:1 ratio to receive tirzepatide maximum tolerated dose 10 mg or 15 mg or placebo. The primary objective of both studies was to demonstrate that tirzepatide is superior in change in apnea-hypopnea index (AHI) from baseline at 52 weeks as compared to placebo. The study was published online in the New England J of Medicine.¹

Patients were enrolled if they had moderate-to-severe OSA, defined as more than 15 events per hour (using the AHI and a body mass index of 30 kg/m² or greater. In study 1, 114 individuals received tirzepatide and 120 received placebo. For study 2, 119 patients received tirzepatide and 114 received placebo. All participants received regular lifestyle counselling sessions about nutrition and were instructed to reduce food intake by 500 kcal/day and to engage in at least 150 min/week of physical activity.

At baseline, 65%–70% of participants had severe OSA, with more than 30 events/hour on the AHI scale and a mean of 51.5 events/h in study 1 and 49.5 in study 2.

By 1 year, patients taking tirzepatide had 27–30 fewer events/hour compared with 4–6 fewer events/hour for those taking placebo. Up to half of those who received tirzepatide in both trials had less than 5 events/h or 5–14 AHI events/h and an Epworth Sleepiness Scale score of 10 or less. This translate to around 40%–50% of patient who were no longer required to use CPAP therapy for the management of their OSA. Patients who received tirzepatide also reported fewer daytime and night-time disturbances, as measured using the Patient-Reported Outcomes Measurement Information System Short Form scale for Sleep-Related Impairment and Sleep Disturbance. Patients in the tirzepatide group also had a decrease in systolic blood pressure from baseline of 9.7 mm Hg in study 1 and 7.6 mm Hg in study 2 at Week 48. Patients on Tirzepatide lost 18%–20% of their body weight.

The most common adverse events were diarrhoea, nausea, and vomiting, which occurred in approximately a quarter of patients taking tirzepatide which were largely mild and moderate in severity. There were two adjudicated-confirmed cases of acute pancreatitis in those taking tirzepatide in study 2.

The SURMOUNT-OSA studies provided a promising new therapeutic option that addresses both respiratory and metabolic complications. It highlights the importance of integrating obesity management in patients with OSA and that the use of combination of CPAP with Tirzepatide could be an optimal treatment for OSA by also targeting obesity-related cardio-metabolic risks. There remains some unanswered questions. It is still not clear whether tirzepatide had an independent effect in the OSA trial or whether the positive results were primarily due to weight loss. What about long-term OSA and cardiovascular disease outcomes? It is however reassuring that the improvement in systolic blood pressure was substantially larger than effects seen with CPAP therapy alone and indicate that tirzepatide may confer a greater reduction in cardiovascular disease risks compared with CPAP therapy alone.