Lifestyle Interventions: What GLP-1 Agonist, Semaglutide and Tirzepatide, Trials Reveal About Sustainable Weight Loss
- Alastair Hunt
- 6 days ago
- 5 min read
Updated: 5 days ago
In recent years, medications like semaglutide (WeGovy, Ozempic) and tirzepatide (Zepbound, Mounjaro) have become prominent tools in the management of obesity. But while headlines often focus on the dramatic weight loss these drugs can produce, an equally crucial component—lifestyle intervention—deserves close attention. Two major studies, STEP 1 (semaglutide) and SURMOUNT-4 (tirzepatide), offer detailed insights into how structured changes in diet and physical activity can work alongside medication to produce and maintain weight loss.
As ever, please talk to your doctor or medical practitioner most familiar with your medical history before implementing any changes in diet, exercise or lifestyle, especially if you are under treatment. Links to all studies at bottom of page.
Lifestyle Support: A Structured and Ongoing Component
Both trials included intensive lifestyle interventions as part of the study design. In STEP 1, participants received individual counselling sessions every four weeks from trained healthcare professionals. These sessions focused on supporting adherence to a reduced-calorie diet- specifically, a deficit of 500 kilocalories per day relative to estimated energy needs. Additionally, participants were encouraged to engage in 150 minutes of physical activity each week, with walking commonly recommended.
To support behavioural consistency, participants tracked their food intake and activity using diaries or smartphone apps. These records were reviewed during each counselling session, allowing adjustments and personal feedback. Importantly, this lifestyle support was consistent across both the semaglutide and placebo groups, ensuring that any weight changes could be attributed more clearly to medication effects in combination with lifestyle advice.
The SURMOUNT-4 trial offered a similarly structured approach. During the entire 88-week study, participants attended regular counselling designed to reinforce the same calorie deficit (approximately 500 kcal/day) and physical activity target (150 minutes per week). These interventions were administered by qualified professionals and tailored to participant needs. Unlike STEP 1, this trial included an open-label lead-in period where all participants received tirzepatide, allowing researchers to observe how participants initially responded to both the medication and lifestyle changes before splitting the group.
What sets SURMOUNT-4 apart is the second phase: a 52-week double-blind period where participants either continued on tirzepatide or switched to placebo, while maintaining the same lifestyle counselling. This unique design allowed researchers to examine the long-term effects of withdrawing medication while continuing lifestyle support.
STEP 1: The Lifestyle-Only Outcome
In STEP 1, even without active medication, lifestyle intervention alone led to measurable weight loss. The placebo group lost an average of 2.4% of their body weight over 68 weeks. About 31% of participants in this group lost at least 5% of their starting weight and 12% lost 10% or more. These results underscore that consistent, professional support with diet and exercise can yield real, if modest, results.
The group receiving semaglutide, however, lost an average of 15% of their body weight, with over 50% achieving losses of 15% or more. This suggests that while lifestyle changes provide a foundation, pharmacotherapy can significantly amplify the benefits when used in tandem with behaviour change.
SURMOUNT-4: Testing the Durability of Lifestyle Support Alone
The design of SURMOUNT-4 allowed for a clear look at how lifestyle intervention performs when medication is discontinued. After losing an average of 21% of body weight during the 36-week tirzepatide lead-in phase, participants were randomised to either continue on the medication or switch to placebo.
Those who switched to placebo and continued only with lifestyle intervention regained an average of 14% of their weight over the next 52 weeks. This finding highlights the difficulty many face in maintaining weight loss with lifestyle changes alone, especially after significant initial success.
In contrast, participants who remained on tirzepatide lost an additional 5.5%, demonstrating that medication can help consolidate early weight loss and prevent regain. Remarkably, 89.5% of those who stayed on tirzepatide maintained at least 80% of their initial weight loss, compared to just 16.6% in the placebo group.
Why Lifestyle Still Matters
Across both trials, the consistent use of structured lifestyle intervention helped standardise care and isolate the effects of medication. But more importantly, it showed that behaviour change remains a vital part of any weight management strategy.
Lifestyle intervention contributed to improved blood pressure, blood glucose, lipid profiles, and quality of life in all groups, even when weight loss was modest. In the semaglutide trial, improvements in physical function scores were observed in both treatment arms, though more pronounced in the semaglutide group.
Crucially, these findings reinforce the idea that lifestyle support shouldn't be sidelined. Even when medications offer potent biological effects, it is the routine of healthier eating, regular movement, and accountability through counselling that anchors lasting progress.
Final Thoughts
These landmark trials highlight a powerful message: lifestyle changes remain central to successful weight management, even when medications are used. While drugs like semaglutide and tirzepatide can significantly boost outcomes, the foundation laid by a structured diet and activity programme is indispensable.
For people seeking meaningful and sustained weight loss, these studies suggest a combined approach offers the best chance of success. Lifestyle interventions alone can initiate change. When paired with medication, they can help achieve and maintain health goals that might otherwise feel out of reach.
Whether your interest is weight loss, healthspan and longevity, to beat chronic illness or to enhance your mental health and well-being, our consultations and programs deliver results that are tailored to your needs.
FOUNDATIONS - our premier whole person health consult - identifies and prioritises the key factors, known and unknown, that affect health and wellbeing. It provides targeted recommendations tailored to you, the individual, and your unique lifestyle.
Stay Healthy,
Alastair
Join us, or scroll down to contact us and learn more about our services:
Achieve your Health Goals
Our health, physical – mental – social - is complex and affected by multiple factors within and outside of your control. Our consults and programmes address the whole person, the root causes of ill health and maximising your health, performance & vitality.
Take the first step. Contact us to arrange an introductory call, to discuss how we can support your journey to health. We are based in Singapore and work with clients globally.
Book a Foundations Consult to assess, identify and prioritise key factors (known and unknown) that affect your health. And receive personalised recommendations on how to address them.
Want to put recommendations into action? Learn more about our programmes for individuals or teams.
Related Studies and Resources
Aronne LJ, Sattar N, Horn DB, Bays HE, Wharton S, Lin WY, Ahmad NN, Zhang S, Liao R, Bunck MC, Jouravskaya I, Murphy MA; SURMOUNT-4 Investigators. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA. 2024 Jan 2;331(1):38-48. doi: 10.1001/jama.2023.24945. PMID: 38078870; PMCID: PMC10714284.
Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989-1002. doi: 10.1056/NEJMoa2032183. Epub 2021 Feb 10. PMID: 33567185.
Kommentare