Tirzepatide works as both a glucagon-like peptide-1 (GLP-1) and a glucose-dependent insulinotropic peptide (GIP) receptor agonist. It is indicated for the treatment of Type 2 Diabetes (T2D), and chronic weight management.
This case study looks at how to use tirzepatide (trade name Mounjaro®) to support patients with obesity and difficult-to-control diabetes.
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 Type 2 Diabetes.
Tevita is a 58-year-old Tongan man living with T2D and presents to your clinic. He works as a police officer. He was asked to book an appointment as his recent blood tests show a worsening HbA1c (now up to 82 mmol/mol).
He was diagnosed with T2D 11 years ago and is currently on insulin glargine (also known as Lantus) once daily, and metformin BD. On further questioning, Tevita admits to symptoms of fatigue and polyuria, especially over the last 3 months. He also notices occasional symptoms of hypoglycaemia, e.g. dizziness and brain fog. He finds it difficult to adhere to his medications, especially his insulin, as he does shift work and so struggles with a regular routine.
Tevita has also been steadily gaining weight since he was first diagnosed with diabetes. He struggles with food noise and the cravings it brings on. Furthermore, he has erratic eating habits due to his shift work and tends to snack on fast food.
Tevita has heard from friends and family that there are several newer medications for diabetes around these days, including some that help with weight loss. He’s interested in knowing whether any of them are suitable for him.
Overview
T2D is a significant health issue in Aotearoa/ New Zealand - approximately 300,000 people live with T2D currently1, and this number is expected to exceed half a million by 20402. As noted by Te Whatu Ora data, “Māori, Pacific, and Indian communities experience a higher prevalence of diabetes, earlier onset, higher mortality and complication rates, and greater health loss compared with other population groups"2.
Left untreated, diabetes can lead to a myriad of micro- and macro-vascular complications, including:
- cardiovascular disease
- cerebrovascular disease (i.e. stroke/TIA)
- renal impairment
- retinopathy
- peripheral vascular disease.
Management of diabetes involves a multi-pronged approach, including:
- Lifestyle factors such as nutrition and physical activity interventions.
- Regular monitoring for glycaemic control and complications, e.g. urine ACR monitoring, foot and retinal screening.
- Pharmacological treatments with appropriate priority on cardio-renal protective agents (e.g. SGLT2 inhibitors, GLP-1 receptor agonists).
- Cardiovascular and renal risk management, optimised blood pressure and lipid management.
- Proactive weight management.
- Education on self-management and psychosocial support, coordinated by a multidisciplinary team.
You review Tevita’s medical background, to determine the best course of action.
Background
- T2D diagnosed on routine screening 11 years ago
- Up to date with retinal and foot screening – no concerns raised
- Hypertension, diagnosed 4 years ago
- Progressive weight gain for approximately 15 years
- Never smoked
- Family history of
- T2D – both parents
- Cardiovascular disease – father died of an MI at age 64.
Medications
- Metformin 1g PO BD started 11 years ago.
- Insulin glargine 16 units SC OD started 5 years ago.
- Candesartan 16 mg PO OD started 4 years ago.
Examination findings today
- Weight 127 kg (up from 122 kg 3 months ago)
- Height 1.82 m
- BMI 38.3 kg/m2
- Blood pressure 134/88
- Heart rate 74 bpm.
Blood glucose records from the last week (he does not take his readings regularly due to shift work):
| Day | Pre-b'fast (fasting) | Post-b'fast | Pre-lunch | Post-lunch | Pre-dinner | Post-dinner | Bedtime |
| Mon | 9.8 | 14.2 | 12.4 | 17.5 | |||
| Tue | 3.8 | 14.5 | |||||
| Wed | 16.7 | 13.2 | |||||
| Thu | 10.7 | 13.6 | |||||
| Fri | 14.1 | ||||||
| Sat | 11.2 | 17.1 | 3.7 | 13.5 | |||
| Sun | 10.5 | 14.8 |
Laboratory findings from 1 week ago
- HbA1c 82 mmol/mol – up from 76 mmol/mol 3 months ago
- Lipids: Total 4.1 mmol/L, HDL 1.5mmol/L, LDL 1.8mmol/L Total/HDL Ratio 2.7
- Creatinine 62 mcmol/L
- EGFR > 90 mL/min/1.73 m²
- 5-year CVD risk –14 %
- Urine ACR 15 mg/mmol (normal <3.5 mg/mmol).
You agree with Tevita that further changes are needed in his medication regime and discuss several options that could be considered:
- Empagliflozin – works as a SGLT-2 inhibitor with good evidence for diabetes control as well as cardio-renal protection3. It may also have a small positive effect on his weight. He would be eligible for Special Authority funding based on his ethnicity and persistently elevated HbA1c despite Diabetes treatment. One negative is that it is a daily tablet, and he may struggle with adherence given his shift work.
- Dulaglutide – a GLP-1 agonist with evidence supporting good glycaemic control and modest weight loss4. There is evidence for cardiovascular risk reduction5. Again, he is eligible for Special Authority funding. It would be administered as a once-weekly injection.
- Semaglutide – a newer generation GLP-1 with better efficacy than dulaglutide for improvement in HbA1c6. However, it is not funded.
- Tirzepatide – a novel GLP-1/GIP agonist. It has superior evidence for glycaemic control and weight loss compared to dulaglutide. It is also administered as a once-weekly dose. However, it is not currently funded.
- Change the insulin regimen to basal/bolus and increase the dosage of his basal insulin. This may provide better blood sugar control. However, there may be an increased risk of hypoglycaemic episodes, and a more frequent insulin regime may not fit with Tevita’s work schedule.
Tevita returns 1 week later, having considered his medication options. He has a cousin in the USA who is currently on Mounjaro and has noticed improved diabetes control and weight loss. He is interested to trial tirzepatide and is willing to self-fund it.
Before he starts, he wants to learn more about how it works and how to administer it.
Mechanism of action
Mounjaro contains the active ingredient tirzepatide. Tirzepatide is a single molecule with actions at two related receptors. It functions as both:
- 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.
- 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.
Efficacy
Tirzepatide has demonstrated improved glycaemic control (reduction in HbA1c) compared to other GLP1 agonists such as semaglutide, liraglutide or dulaglutide6,7.
Tirzepatide is also superior to semaglutide for weight loss8. When compared to adding bolus insulin for patients with inadequately controlled type 2 diabetes established on metformin and basal insulin, tirzepatide showed a superior reduction in HbA1c and body weight, with improved patient-reported quality of life9. Also, there was a significantly lower rate of clinically significant hypoglycaemia compared to adding bolus insulin.
Tirzepatide has established cardiovascular safety, having demonstrated non-inferiority to dulaglutide for cardiovascular outcomes10.
Use in T2D in adults
Tirzepatide is indicated for the treatment of adults with insufficiently controlled T2D as an adjunct to diet and exercise11.
It can be administered as monotherapy or in conjunction with other medications, provided there are no contraindications (see below).
Administration and Dosing
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 doses11.
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; instead, they should return to the 2.5mg dose and resume up-titration.
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 Data sheet for further information11.
Titration schedule
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 in a step wise manner every 4 weeks, to a maximum dose of 15 mg.
If individuals are experiencing side effects, dose titration should be slowed, and the dosage should not be increased until these abate. Not everyone can tolerate the maximum dose, and management at a lower dose is acceptable, provided the desired outcomes are achieved.
If adequate glycaemic control is still not achieved, alternative treatments may be required.
After further discussion on administration and dosing, Tevita feels confident to start tirzepatide. Despite his shift work, he feels confident that he can adhere to the once-weekly injection regime.
You agree to start Tevita on 2.5 mg of tirzepatide, SC weekly for 4 weeks. After this, he is to return for a follow-up visit.
Tevita would like to know more about the safety profile of tirzepatide. Will he have more hypoglycaemic episodes on tirzepatide?
Adverse effects, Cautions and Contra-indications
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 effects11 (>10% of clinical trial participants):
- nausea
- diarrhoea
- abdominal pain
- constipation.
Common side effects11 (1 to 10% of clinical trial participants):
- dyspepsia
- flatulence
- GORD
- fatigue
- injection site reaction.
Cautions
Hypoglycaemia in patients with T2D
Patients who receive tirzepatide as well as insulin or sulphonylureas (e.g. gliclazide) are at increased risk of hypoglycaemia11. Doses of such medicines may need to be adjusted to reduce the risk (see below).
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 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 not a reason to stop 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 should be exercised 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.
|
Absolute contraindications
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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 far11. 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 escalation11.
You have a detailed discussion about the common side effects of tirzepatide, and the chances of developing hypoglycaemia, since he is on insulin. He decides to wait until his next week off work to start tirzepatide, so he can take his blood sugar readings more often.
At this stage, due to the significantly raised HbA1c, you decide to continue the current dose of Lantus and closely monitor his blood sugar levels.
Tevita is satisfied with the information given about tirzepatide. Before he leaves, he would like to discuss what more lifestyle changes he can make to help manage his diabetes and his weight.
You decide to refer him to your local green prescription service, which will offer Tevita access to group exercise programs and healthy cooking classes. Your practice also has a health improvement practitioner who can offer one-on-one diet and lifestyle advice - Tevita is keen to be referred to them.
Management of co-morbidities and lifestyle intervention
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.
Practice Point
Patients should be offered lifestyle advice and support alongside pharmacotherapy to optimise outcomes, including options such as a green prescription and dietetic support. Many patients achieve significant lifestyle changes through pharmacotherapy and advice from their well-informed primary care team, with whom they enjoy a trusting therapeutic relationship.
- Healthify has resources on weight loss as well as reviewed weight management apps.
- Free healthy cookbooks, Heart Foundation NZ
- Green Prescriptions, Health New Zealand
Weight stigma and bias
Weight stigma and bias have substantial adverse impacts on people living with obesity, affecting psychological wellbeing, physical health, and engagement with healthcare12.
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.
Tevita returns to your clinic 1 month later for a follow-up appointment. He has seen the HIP and has made a diet plan, focusing on diet changes, including smaller portion sizes and reduced carbohydrates. He is also engaged in a regular exercise regime through the Green Prescription Programme.
Tevita started tirzepatide 1 week ago, while he was on leave from work. He has noticed that his appetite and food noise have certainly reduced. While he has not experienced any GI side effects, he has had symptoms of hypoglycaemia more often.
He produced the following BSL readings from the last week:
| Day | Pre-b'fast (fasting) | Post-b'fast | Pre-lunch | Post-lunch | Pre-dinner | Post-dinner | Bedtime |
| Mon | 4.8 | 4.1 | 8.5 | 5 | 4.4 | ||
| Tue | 3.6 | 6.8 | 3.9 | 7.9 | 8.4 | ||
| Wed | 4.2 | 7.5 | 4.5 | 4.8 | 9 | 4.3 | |
| Thu | 3.4 | 6.9 | 3.7 | 7.6 | 4.3 | 3.8 | |
| Fri | 4.4 | 5.1 | 9.5 | 4.6 | |||
| Sat | 3.8 | 6.5 | 3.5 | 7.4 | 8 | 3.9 | |
| Sun | 4.1 | 7.1 | 3.8 | 4.6 | 8.7 |
While you are both reassured by his improved BSL readings, his hypoglycaemic episodes are cause for concern.
Tevita agrees to a step-wise reduction in his insulin glargine, of 2 units every 3 to 4 days until his hypo’s go away.
You arrange for the practice nurse to contact Tevita on a weekly basis to provide ongoing support as he adjusts his insulin dose.
You agree to meet with Tevita again in 3 week’s time.
Management of hypoglycaemia
Tirzepatide monotherapy is generally not associated with hypoglycaemia; however, the risk of hypoglycaemic events increases when co-administered with insulin secretagogues (e.g. sulphonylureas) or exogenous insulin. As patients achieve weight loss on tirzepatide, they are also likely to achieve better glycaemic control, reducing the need for such medicines but again increasing the risk of hypoglycaemia.
Therefore, close monitoring of blood glucose levels is required when initiating and up-titrating tirzepatide.
Some sources suggest proactively reducing the dose of insulin by 20% when initiating incretins such as tirzepatide, especially if the baseline HBA1c is below 64 mmol/mol13.
Tevita returns to your practice 3 weeks later. He has continued with tirzepatide on 2.5 mg SC weekly for 1 month now.
With the help of the practice nurse, he has titrated his insulin glargine down to 8 units SC OD.
His appetite is certainly reduced, and he has noticed that his clothes feel looser already. He has made an effort to eat smaller, more nutritionally balanced meals and is maintaining his exercise levels.
His BSL readings from the last week are as follows:
| Day | Pre-b'fast (fasting) | Post-b'fast | Pre-lunch | Post-lunch | Pre-dinner | Post-dinner | Bedtime |
| Mon | 6.8 | 9.5 | 7.4 | ||||
| Tue | 6.8 | 11.5 | 7.6 | 12.3 | |||
| Wed | 6.5 | 9 | 5.9 | 10.2 | 6.8 | 11 | 7.2 |
| Thu | 7.8 | 8 | 12.9 | 8.6 | |||
| Fri | 6.9 | 9.8 | 6.4 | 10.9 | 7.3 | 11.8 | 7.7 |
| Sat | 7.6 | 12.8 | |||||
| Sun | 7.4 | 10.5 | 7.8 | 8.3 |
On exam today:
- Weight 124 kg – a 3 kg loss
- Height 1.82 m
- BMI 37.4 kg/m2
- Blood pressure 130/82
- Heart rate 70 bpm
Overall, Tevita is very happy with how tirzepatide is going. You agree to increase the dose to 5 mg sub-cut weekly and have another follow-up in one month.
Tevita will continue to check his BSLs frequently and liaise with the practice nurse about his insulin levels. He is keen to reduce the insulin further or even stop it completely if possible. You counsel him again on the administration of the injections and side effects to monitor for.
You also discuss introducing empagliflozin and atorvastatin given his microalbuminuria and cardiovascular risk, aiming for LDL of less than 1.4.
Tevita will consider this and would like to discuss further at the next visit. You also agree to do repeat lab work, including renal function, lipids, urine ACR and HbA1c, before the next visit.
This MedCase was created by Dr Pulasthi Mithraratne, MBChB, PGDipPaed, FRNZCGP, with expert review by Dr Chaey Leem, Bariatric Doctor.
References
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