Is lifestyle counseling needed with the more effective second-generation nutrient-stimulated, hormone-based medications like semaglutide and tirzepatide?
If so, how intensive does the counseling need to be, and what components should be emphasized?
These are the clinical practice questions at the top of mind for healthcare professionals and researchers who provide care to patients who have overweight and/or obesity.
This is what we know. Lifestyle management is considered foundational in the care of patients with obesity.
Because obesity is fundamentally a disease of energy dysregulation, counseling has traditionally focused on dietary caloric reduction, increased physical activity, and strategies to adapt new cognitive and lifestyle behaviors.
On the basis of trial results from the Diabetes Prevention Program and the Look AHEAD studies, provision of intensive behavioral therapy (IBT) is recommended for treatment of obesity by the Centers for Medicare & Medicaid Services and by the US Preventive Services Task Force (Moyer VA; US Preventive Services Task Force).
IBT is commonly defined as consisting of 12-26 comprehensive and multicomponent sessions over the course of a year.
Reaffirming the primacy of lifestyle management, all antiobesity medications are approved by the US Food and Drug Administration as an adjunct to a reduced-calorie diet and increased physical activity.
The beneficial effect of combining IBT with earlier-generation medications like naltrexone/bupropion or liraglutide demonstrated that more participants in the trials achieved ≥ 10% weight loss with IBT compared with those taking the medication without IBT: 38.4% vs 20% for naltrexone/bupropion and 46% vs 33% for liraglutide.
Although there aren’t trial data for other first-generation medications like phentermine, orlistat, or phentermine/topiramate, it is assumed that patients taking these medications would also achieve greater weight loss when combined with IBT.
The obesity pharmacotherapy landscape was upended, however, with the approval of semaglutide (Wegovy), a glucagon-like peptide-1 (GLP-1) receptor agonist, in 2021; and tirzepatide (Zepbound), a GLP-1 and glucose-dependent insulinotropic polypeptide dual receptor agonist, in 2023.
These highly effective medications harness the effect of naturally occurring incretin hormones that reduce appetite through direct and indirect effects on the brain. Although the study designs differed between the STEP 1 and STEP 3 trials, the addition of IBT to semaglutide increased mean percent weight loss from 15% to 16% after 68 weeks of treatment (Wilding JPH et al; Wadden TA).
Comparable benefits from the STEP 3 and SURMOUNT-1 trials of adding IBT to tirzepatide at the maximal tolerated dose increased mean percent weight loss from 21% to 24% after 72 weeks (Wadden TA; Jastreboff AM). Though multicomponent IBT appears to provide greater weight loss when used with nutrient-stimulated hormone-based therapeutics, the additional benefit may be less when compared with first-generation medications.
So, how should we view the role and importance of lifestyle management when a patient is taking a second-generation medication? We need to shift the focus from prescribing a calorie-reduced diet to counseling for healthy eating patterns.
Because the second-generation drugs are more biologically effective in suppressing appetite (ie, reducing hunger, food noise, and cravings, and increasing satiation and satiety), it is easier for patients to reduce their food intake without a sense of deprivation. Furthermore, many patients express less desire to consume savory, sweet, and other enticing foods.
Patients should be encouraged to optimize the quality of their diet, prioritizing lean protein sources with meals and snacks; increasing fruits, vegetables, fiber, and complex carbohydrates; and keeping well hydrated. Because of the risk of developing micronutrient deficiencies while consuming a low-calorie diet — most notably calcium, iron, and vitamin D — patients may be advised to take a daily multivitamin supplement. Dietary counseling should be introduced when patients start pharmacotherapy, and if needed, referral to a registered dietitian nutritionist may be helpful in making these changes.
Additional counseling tips to mitigate the gastrointestinal side effects of these drugs that most commonly occur during the early dose-escalation phase include eating slowly; choosing smaller portion sizes; stopping eating when full; not skipping meals; and avoiding fatty, fried, and greasy foods. These dietary changes are particularly important over the first days after patients take the injection.
The increased weight loss achieved also raises concerns about the need to maintain lean body mass and the importance of physical activity and exercise counseling. All weight loss interventions, including dietary restriction, pharmacotherapy, or bariatric surgery, result in loss of fat mass and lean body mass.
The goal of lifestyle counseling is to minimize and preserve muscle mass (a component of lean body mass) which is needed for optimal health, mobility, daily function, and quality of life. Counseling should incorporate both aerobic and resistance training. Aerobic exercise (eg, brisk walking, jogging, dancing, elliptical machine, and cycling) improves cardiovascular fitness, metabolic health, and energy expenditure. Resistance (strength) training (eg, weightlifting, resistance bands, and circuit training) lessens the loss of muscle mass, enhances functional strength and mobility, and improves bone density (Gorgojo-Martinez JJ et al; Oppert JM et al).
Robust physical activity has also been shown to be a predictor of weight loss maintenance. A recently published randomized placebo-controlled trial demonstrated the benefit of supervised exercise in maintaining body weight and lean body mass after discontinuing 52 weeks of liraglutide treatment compared with no exercise.
Rather than minimizing the provision of lifestyle management, using highly effective second-generation therapeutics redirects the focus on how patients with obesity can strive to achieve a healthy and productive life.
A version of this article first appeared on Medscape.com.