Ozempic and Mounjaro: Evidence, Safety, and Appropriate Use

Semaglutide and tirzepatide are newer medications used in the treatment of obesity and type 2 diabetes. Both act on incretin pathways that influence appetite, satiety, and glucose regulation. They have generated strong interest because of meaningful effects on body weight and metabolic risk factors in clinical trials. This article reviews the current evidence, typical clinical considerations, and practical issues that arise when these therapies are discussed with patients.

Background and mechanism

Semaglutide is a glucagon-like peptide‑1 (GLP‑1) receptor agonist. Tirzepatide is a dual agonist of the glucose-dependent insulinotropic polypeptide (GIP) and GLP‑1 receptors. Both molecules slow gastric emptying, enhance satiety signals, and influence energy intake. A portion of their benefit in type 2 diabetes is driven by improved insulin secretion and reduced glucagon, but the body‑weight effects appear to be primarily mediated through appetite regulation.

Efficacy from randomized trials

Multiple large randomized controlled trials have evaluated once‑weekly semaglutide at 2.4 mg and tirzepatide at 5–15 mg in people with obesity or overweight. These trials report average weight loss in the 10–22 percent range at approximately 68–72 weeks, with variability based on dose, baseline characteristics, and adherence. In head‑to‑head data now emerging, tirzepatide has shown greater mean weight loss than semaglutide, although individual response differs. Alongside weight change, participants typically see improvements in waist circumference, blood pressure, lipid parameters, and glycemic control. Importantly, the trials were lifestyle‑supported, so outcomes reflect medication plus structured nutrition and activity guidance.

Safety profile and tolerability

The most common adverse effects are gastrointestinal. Nausea, vomiting, early satiety, and constipation are dose‑related and often improve with slower titration and food‑timing adjustments. Less frequent effects include gallbladder disease, delayed gastric emptying that may affect the timing of other oral medications, and rare pancreatitis. The label cautions against use in people with a personal or family history of medullary thyroid carcinoma or MEN2. In clinical practice, careful dose escalation and counseling on meal size and pace reduce early discontinuation.

Who tends to benefit

Trials have included participants with and without type 2 diabetes. Those with higher baseline weight and cardiometabolic risk factors often derive the largest absolute improvements in health markers. The medications can be helpful for patients who have struggled to achieve or maintain weight loss with nutrition and activity alone, particularly when obesity-related comorbidities are present. These drugs are not a universal solution. They work best when combined with structured lifestyle change and realistic maintenance planning.

Practical considerations

Dose titration reduces adverse effects. A gradual step‑up schedule gives the gastrointestinal tract time to adapt. Counseling should include practical guidance on portion size, protein intake to protect lean mass, hydration, and fiber. Monitoring includes weight, waist circumference, blood pressure, and when relevant, A1c and lipid panels. Because weight loss can alter medication needs, antihypertensive and hypoglycemic therapy sometimes requires adjustment over time.

What happens after stopping therapy

Weight regain is common after medication cessation, particularly if underlying habits have not changed. This is consistent with long‑standing observations across weight‑loss interventions. If the decision is made to taper, a plan should be in place for nutrition structure, activity targets, sleep, and regular check‑ins. Some individuals prefer sustained low‑dose maintenance; others discontinue after a defined period while prioritizing intensive lifestyle strategies.

Equity and access

Coverage varies by jurisdiction and insurer. Out‑of‑pocket cost can be a barrier. When medications are not accessible, many of the same metabolic benefits can still be achieved through consistent dietary structure, progressive resistance and aerobic training, sleep improvement, and stress management, though results may be slower and less pronounced for some patients.

Key counseling points

Set expectations early. Medications can reduce appetite and support adherence, but they do not replace the need for nutrition planning and physical activity. Muscle‑preserving strategies matter during weight loss to maintain resting energy expenditure. Side effects are most prominent during dose escalation and usually improve. The goal is long‑term health, not only short‑term weight change.

Summary

Semaglutide and tirzepatide represent important additions to the medical management of obesity. Randomized trials show clinically meaningful weight loss and improvements in cardiometabolic risk factors. Benefits are maximized when therapy is paired with individualized nutrition, realistic activity targets, and a maintenance strategy. Ongoing research will clarify long‑term outcomes, comparative effectiveness, and best practices for tapering or continuation.

Our Kitchener weight loss clinic safely prescribes semaglutide and tirzepatide under physician-supervision.

References

Wilding JPH et al. Once‑weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384:989–1002. doi:10.1056/NEJMoa2032183. PMID: 33567185.

Jastreboff AM et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT‑1). N Engl J Med. 2022;387:205–216. doi:10.1056/NEJMoa2206038. PMID: 35658024.

Bellicha A et al. Effect of exercise training on weight loss, body composition and metabolic outcomes. Obes Rev. 2021;22(8):e13298. PMID: 34324779.

Lafontant K et al. Comparison of concurrent, resistance, or aerobic training on body composition. Int J Obes (Lond). 2025;49: (systematic review and meta‑analysis). PMID: 40405489.

NEJM. Tirzepatide vs semaglutide for weight reduction. 2025; (head‑to‑head data). doi:10.1056/NEJMoa2416394.

Serving patients across Kitchener, Waterloo, Cambridge, Guelph, and surrounding communities including the Toronto/GTA corridor and London, Ontario.