Difficult-to-treat obstructive sleep apnoea in adults

While OSA is the most likely diagnosis, alternative diagnoses to consider include:

• Obesity hypoventilation syndrome
• Central sleep apnoea
• Narcolepsy

However, each is less consistent with Mark's presentation:

• Obesity hypoventilation syndrome is associated with chronic hypercapnia during the daytime. While symptoms can be similar to OSA, it is associated with morning headaches and other daytime symptoms, which are lacking in Mark’s case. Patients usually have concomitant heart disease (e.g. heart failure), and it is usually associated with a higher BMI (greater than 45) in Pākehā patients like Mark. 
• Central sleep apnoea is due to impaired central respiratory drive and would be associated with other conditions such as heart failure, stroke or medication use e.g. opioids. 
• Narcolepsy may be associated with severe daytime sleepiness, unrefreshing naps, sleep-related hallucinations, vivid dreams and sleep paralysis, none of which are reported by Mark. Patients may also have emotion-driven transient muscle weakness (cataplexy). Narcolepsy usually presents in one’s teens and twenties. 

Common symptoms associated with sleep apnoea include:

• Waking up feeling unrefreshed.
• Daytime somnolence.
• Reports of loud snoring and apnoeic episodes by bed partners.

Please note that females with OSA may have different presenting features, e.g. nocturia, mood changes, insomnia, fragmented sleep and daytime fatigue.

OSA is associated with several negative health outcomes including:

• Cardiovascular – hypertension, coronary artery disease, heart failure.
• Neurological – especially stroke, cognitive issues (concentration, vigilance and attention).
• Metabolic – including diabetes and dyslipidaemia.

Risk factors for OSA include:

• having a raised BMI/obesity
• male sex
• advanced age
• smoking.

Current estimates of prevalence are about 10% in women and 20% in men, but rates are rising, particularly due to rising obesity rates globally¹. 

STOP-BANG Questionnaire and Epworth Sleepiness Scale (ESS) are both useful tools.

The STOP-Bang Questionnaire is an eight-question screening tool used by clinicians to check if a person is at risk for OSA.

The Epworth Sleepiness Scale is a short questionnaire used to measure excessive daytime sleepiness.
 

From Obstructive sleep apnoea in adults bpac^nz (2012)

Mounjaro contains the active ingredient tirzepatide. Tirzepatide is a single molecule that acts on two related receptors. It functions as both:

1. A GLP-1 receptor agonist - with the same mechanism as dulaglutide (Trulicity), liraglutide (Victoza/Saxenda) and semaglutide (Ozempic/Wegovy).  GLP-1 is released from the gut in response to the detection of ingested nutrients and acts to enhance insulin release, reduce hunger and slow gastric emptying.
2. A GIP analogue – GIP acts similarly to GLP-1 to reduce hunger, enhance insulin secretion, and improve insulin sensitivity. Unlike GLP-1, GIP acts to reduce nausea in the context of GLP-1 receptor agonism.

While structurally similar to both endogenous GLP-1 and GIP, tirzepatide has a much longer half-life (approx. 5 days, compared to only a few minutes for the native hormones). This enables once-weekly dosing. 

Tirzepatide is indicated for the treatment of Type 2 Diabetes (T2D) and chronic weight management. Tirzepatide is now available in New Zealand but is not funded. At the time of writing, PHARMAC is considering an application for funding of tirzepatide for the treatment of T2D.

The efficacy of tirzepatide was demonstrated in the SURMOUNT-1 trial, with a mean body weight loss of 15.0% to 20.9% over 72 weeks of treatment at doses ranging from 5 mg to 15 mg weekly (compared with a loss of 3.1% in the placebo group)². Tirzepatide is superior to semaglutide for weight loss³ and glycaemic control⁴. It has established cardiovascular safety, having demonstrated non-inferiority to dulaglutide⁵ for cardiovascular outcomes.

Furthermore, the SURMOUNT-OSA⁶ trial demonstrated that in patients with moderate-to-severe OSA, tirzepatide produced a clinically significant improvement in AHI (approximately 50% reduction), hypoxic burden (PSG outcome), and sleep-related quality-of-life scores, along with weight loss (approximately 20%). 

Tirzepatide is administered via subcutaneous injection using a pre-filled pen. The pen is available in pre-mixed doses of 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg. Each pen contains four doses⁷.

Tirzepatide is administered once weekly at any time of day, with or without meals. It is injected subcutaneously into the abdomen or thigh (it is recommended to rotate sites). Patients can be trained to self-administer the injections in their own home and will need a sharps container for safe disposal of needles.

If a dose is missed, it should be administered as soon as possible. However, if the next dose is less than 3 days away, the patient should skip the missed dose and administer the next dose on the usual day. If multiple doses are missed the patient should not resume their previous dose and should instead return to the 2.5mg dose and begin up-titration again.

Much like insulin and GLP-1 receptor agonists, tirzepatide should be stored in the refrigerator (2-8 degrees Celsius) until first use, after which time it can be left at room temperature (below 30 degrees) for up to 30 days. Refer to the NZ Medsafe Data⁷ sheet for further information. 

Patients will usually begin on 2.5 mg SC weekly for 4 weeks before increasing to 5 mg SC weekly. In discussion with the clinician, the patient may choose to increase their dose stepwise every 4 weeks, up to a maximum of 15 mg. 

If individuals are experiencing side effects, dose titration should be slowed, and the dosage should not be increased until the side effects abate. Not everyone can tolerate the maximum dose, and management at a lower dose is acceptable, provided the desired outcomes are achieved.

Given the mode of action, many of the common side effects are related to the gastrointestinal system and reduced oral intake. Clinicians should also be mindful of rarer, but more significant side effects.

Adverse effects

Very common side effects⁷ (>10% of clinical trial participants):

• nausea
• diarrhoea
• abdominal pain
• constipation.

Common side effects⁷ (1 to 10% of clinical trial participants):

• dyspepsia
• flatulence
• GORD
• fatigue
• injection site reaction.

Cautions

Acute pancreatitis
Although rare, patients should be informed of the risk of pancreatitis and to observe for symptoms i.e. epigastric pain radiating to the back, nausea/vomiting, and abdominal bloating.

Tirzepatide can be carefully considered for patients with a history of pancreatitis where the cause is known and treatable, e.g. gallstone pancreatitis. When acute pancreatitis develops following initiation of tirzepatide without a known trigger, treatment must be discontinued.

Routine monitoring of pancreatic enzymes is not recommended, as asymptomatic elevations are common and do not warrant stopping treatment.

Dehydration
Dehydration is a risk due to reduced appetite and GI side effects, leading to fluid depletion and renal impairment.

Clinicians may want to monitor renal function when initiating and up-titrating tirzepatide, especially if the patient reports GI side effects. It is important to counsel the patient on the risk of dehydration and ensure adequate fluid intake. 

Visual issues
In patients with diabetes, a rapid improvement in glucose control may lead to a worsening of diabetic retinopathy.

Caution is warranted in patients with known retinopathy. There have been reports of a very rare optic condition called non-arteritic anterior ischaemic optic neuropathy (NAION) which causes sudden painless vision loss, although the association is not entirely clear.

Other cautions to consider

• Past or present history of disordered eating behaviour.
• Inflammatory bowel disease.
• Diabetic gastroparesis.
• Age ≥85 years.
• There is no efficacy/safety data available for children/adolescents aged under 18, in relation to tirzepatide and weight management
• History of gallstones without cholecystectomy – one should monitor for gallstone-related complications. Patients on tirzepatide have an increased incidence of gallstones, and significant weight loss is a risk factor for gallstone formation itself. Patients need to be counselled appropriately, and the symptoms of biliary colic should be discussed early to avoid complications.
• Use of tirzepatide in patients with severe renal (CKD5) and liver impairment is limited. Patients with CKD4 should be monitored very closely.

Drug interactions
As tirzepatide works to delay gastric emptying, there is a theoretical impact on the rate of absorption of oral medications with a narrow therapeutic index, although this has not been borne out in trial data so far⁷.

It is still recommended to monitor patients on such medications (e.g. warfarin and digoxin), especially when initiating tirzepatide.

Oral contraceptive levels were noted to be reduced in response to co-administration of tirzepatide, and it is recommended to add a barrier form of contraception for 4 weeks after initiation and 4 weeks after each dose escalation⁷.
 

Medications such as tirzepatide need to be prescribed in conjunction with a healthy, well-balanced diet and increased physical activity to promote holistic care, improve overall wellbeing, and minimise side effects. 

Weight stigma and bias have substantial adverse impacts on people living with obesity, affecting psychological wellbeing, physical health, and engagement with healthcare⁸.

Experiences of stigma such as blaming, stereotyping, or assuming poor self-discipline are associated with increased depression, anxiety, and disordered eating, and paradoxically with weight gain and avoidance of health services. In clinical contexts, weight bias can lead to poorer patient–clinician communication, reduced trust, delayed diagnoses, and underuse of preventive care.

Clinicians can reduce weight stigma by adopting person‑first language (e.g. “person with obesity”), focusing on health‑promoting behaviours rather than weight alone, and recognising obesity as a complex, chronic disease influenced by biological, social, and environmental determinants.

This MedCase was created by Dr Pulasthi Mithraratne, MBChB, PGDipPaed, FRNZCGP, with expert review by Professor Brendon Yee, Clinical Professor, MBChB FRACP PhD FAPSR, Respiratory and Sleep Physician.