Mounjaro and Zepbound (tirzepatide): dual-hormone therapy, results, and real-world use

Tirzepatide is a once-weekly injectable that activates both the GIP and GLP-1 receptors. In Canada, Mounjaro is approved for type 2 diabetes. Zepbound is the brand name for tirzepatide with the obesity indication; it has been approved and launched in Canada for chronic weight management. It is one of the most powerful weight loss agents in 2025.

In the SURMOUNT-1, clinical trial adults with obesity or overweight without diabetes lost a mean of about 15 to 21 percent of body weight over 72 weeks across doses, compared with about 3 percent on placebo. That level rivals bariatric procedures at the low end. SURMOUNT-4 asked a practical question: after initial weight reduction on tirzepatide, what happens if you stop. People who continued medication maintained and deepened weight loss; those switched to placebo regained substantially. SURMOUNT-3 examined re-introducing tirzepatide after intensive lifestyle-induced weight loss; adding the drug produced further clinically meaningful loss. The consistent theme is that ongoing therapy maintains the metabolic changes that lower appetite and improve insulin sensitivity.

For diabetes, tirzepatide reduces A1c robustly, permits de-intensification of other glucose-lowering agents, and produces weight loss that improves blood pressure and lipids. For obesity without diabetes, the labeled Zepbound doses are titrated to 5, 10, or 15 mg weekly, with slow ramps to improve tolerability. As with GLP-1 monotherapy, protein intake should be adequate to protect lean mass, and resistance training helps preserve strength during weight loss.

Safety and counseling mirror the class with a few specifics. GI symptoms are common during up-titration and usually respond to slower dose increases, smaller meals, and attention to hydration. There is a class warning about risk of thyroid C-cell tumors based on rodent data, and a contraindication in people with personal or family history of medullary thyroid carcinoma or MEN2. Do not combine with DPP-4 inhibitors. If a patient uses prandial insulin or a sulfonylurea, plan dose reductions as intake falls. Women who could become pregnant need a clear plan, because weight loss drugs are not continued during pregnancy.

Practical tips improve outcomes. Ask about reflux and gallbladder history before you start. Encourage protein targets of roughly 1.6 to 2.2 g/kg of goal body weight and a high-fiber diet. Set a step floor and two brief strength sessions per week so fatigue does not lead to total inactivity. Address alcohol early. Late-evening drinks plus delayed gastric emptying push sleep and reflux in the wrong direction. If a patient is lean with insulin resistance and wants a small reduction in visceral fat, set expectations. The drug is not a license to under-eat protein and skip training. If the goal is obesity treatment with comorbidities, the benefit is more obvious.

What to measure. Baseline and periodic A1c in diabetes, fasting lipids, blood pressure, and body weight trend in all patients. In obesity treatment, expect early changes in appetite and later changes in waist circumference and blood pressure. Be ready to down-titrate antihypertensives as needed. If a patient has suspected sleep apnea, screen early; weight loss can lower pressure requirements for CPAP.

The larger picture is maintenance. SURMOUNT-4’s design shows that stopping therapy leads to regain. That is not unique to tirzepatide; it is what happens when the biological drivers of hunger and energy expenditure are no longer modulated. Framing obesity as a chronic condition sets appropriate expectations and reduces the guilt people feel when weight creeps up after stopping a drug.

References

1. Mounjaro Product Monograph, Health Canada. HRES PDF

2. SURMOUNT-1. N Engl J Med 2022. New England Journal of Medicine

3. SURMOUNT-4. JAMA 2024. JAMA Network

4. SURMOUNT-3. Nat Med 2023. Nature

5. Zepbound approval and availability in Canada.

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