Tirzepatide produced greater average weight loss than semaglutide in a direct obesity trial. Retatrutide has promising results, but remains investigational and needs a different interpretation. 1 2

The useful comparison is not simply single versus dual versus triple agonist. It is what was tested, in whom, against which comparator, and with what limitations.

Mechanism comparison

Semaglutide activates GLP-1 receptors. It reduces hunger and energy intake, supports glucose-dependent insulin release and can delay early gastric emptying. Wegovy is its weight-management formulation. 3

Tirzepatide activates GLP-1 and GIP receptors. GIP means glucose-dependent insulinotropic polypeptide. Tirzepatide affects appetite and glucose regulation, including insulin secretion and sensitivity. 4

GIP receptors also occur in fat tissue. That helps explain research interest in the pathway, but receptor location alone does not establish a clinical advantage. 4

Retatrutide activates GLP-1, GIP and glucagon receptors. Glucagon activity is being studied for effects on energy metabolism and liver fat, alongside the other pathways. 5

A 98-person liver-fat substudy found reductions with retatrutide versus placebo. It did not isolate glucagon's contribution or compare retatrutide with tirzepatide. Energy-expenditure findings discussed were preclinical. 5

For the broader background, see how GLP-1 agonists work.

Clinical trial data

Semaglutide versus tirzepatide: direct evidence

SURMOUNT-5 randomised 751 adults with obesity, without diabetes, to weekly tirzepatide or semaglutide for 72 weeks. 1

Participants received their maximum tolerated trial dose: tirzepatide 10 or 15 mg, or semaglutide 1.7 or 2.4 mg. Average weight reductions were 20.2% and 13.7%, respectively. These are study doses, not prescribing advice. 1

This was an open-label, Lilly-funded study. It supports a weight-loss difference under those conditions, not a guarantee for individuals or a conclusion about every dose, diabetes population or health outcome. 1

Retatrutide: substantial results, different comparisons

In May 2026, Lilly reported TRIUMPH-1 results in adults with obesity or overweight and a related condition, without diabetes. At 80 weeks, the 12 mg group lost an average 28.3%, versus 2.2% with placebo. 6

Those headline figures use an efficacy estimand: an analysis estimating effects if participants remained on treatment without prohibited weight-management therapies. They are not an expected result for every person starting treatment. 6

In July 2026, Lilly also announced positive TRIUMPH-2 and TRIUMPH-3 results in populations with type 2 diabetes or established cardiovascular disease. These were manufacturer topline reports. 2

Different populations, durations and analysis methods prevent treating these figures as a three-way ranking. Placebo-controlled retatrutide studies do not establish superiority over semaglutide or tirzepatide. 1 2 6

Side effect profiles

Nausea, vomiting, diarrhoea and constipation occur with all three. In SURMOUNT-5, gastrointestinal events were usually mild to moderate and occurred mainly during dose escalation. 1 2

Retatrutide reports also include dysaesthesia, meaning altered skin sensation. Some participants stopped treatment because of adverse events. Greater weight loss does not make tolerability unimportant. 2

Semaglutide and tirzepatide carry warnings about pancreatitis and dehydration-related kidney problems. Severe or persistent abdominal pain, repeated vomiting or inability to keep fluids down needs prompt medical assessment. 3 4

If you also use insulin or a sulfonylurea, discuss low-blood-glucose risk with your prescriber. Do not change those medicines yourself. 4

Nutritional implications

Reduced intake can make nutrient needs harder to meet. Lean mass includes tissues other than skeletal muscle, so a lean-mass change is not a direct muscle measurement. 7

The comparative studies above do not establish a proportional increase in muscle loss or micronutrient deficiency with each additional receptor. 1 2

Practical priorities include:

  • Include protein foods such as yoghurt, eggs, fish, tofu or beans. 7
  • Use smaller meals if needed, while retaining food variety and adequate energy. 7
  • Combine protein intake with resistance training suited to your capacity. 7
  • Discuss persistent poor intake, supplements or targeted blood tests with your clinician or dietitian. 7

Protein targets need individualisation, not an automatic increase for a newer medicine. BIA estimates body composition; it does not directly measure muscle. Track strength and function too. 7

See what GLP-1 trials show about muscle for the measurement distinctions.

Availability in New Zealand

Information checked on 6 September 2026.

Wegovy's first NZ approval was 20 March 2025. Mounjaro's was 22 December 2025, with indications for type 2 diabetes and chronic weight management in eligible adults. 3 4

Pharmac states that neither product is publicly funded. Approval and funding do not establish local stock: ask your pharmacy about availability and private cost. 8

Retatrutide remains investigational, not an approved NZ prescribing option. Medsafe's 21 May 2026 advisory specifically warns about black-market products sold as retatrutide. 2 9

The advisory cites international reports of fatal overdose, contamination and serious adverse effects. A “research purposes only” label does not establish safety or authorise personal use. 9

For access detail, see GLP-1 access in New Zealand.

What this means for you

Use these findings to discuss treatment goals, medical history, tolerability and access with your prescriber, rather than choosing from headline weight-loss percentages. 3 4 8

After a prescribed switch, review appetite, intake, symptoms and strength. Adjust nutrition to observed changes rather than automatically increasing protein or scan frequency. 7

If you want help implementing the food and training basics alongside prescribed treatment, explore our nutrition coaching.