top of page

Individualised obesity therapy - tailoring interventions to a person's phenotypes

Phenotype-tailored lifestyle interventions may result in significant weight loss according to the results from a pilot study of 165 people by Mayo Clinic researchers. The study examined the effectiveness of two different approaches to weight loss: a standard lifestyle intervention (SLI) and phenotype-tailored lifestyle intervention (PLI).

Andre Acosta

"The results stress the relevance of identifying the underlying cause of obesity as a complex disease with many factors," explained Dr Andre Acosta, a Mayo Clinic obesity researcher and the study's last author. "The results of this study support the need for an actionable, phenotype-based classification [of patients in obesity treatment] rather than relying only on the number on the scale, body measurements or [if they have] obesity-related diseases, such as heart disease, high blood pressure and certain cancers."

SLI included a reduced diet, exercise and behaviour therapy. PLI was based on phenotypes and included different interventions depending on the person's predominant underlying cause of obesity. A diet based on phenotypes considers a person's genetic and phenotypic characteristics to create a tailored eating plan meant to optimise health and well-being.

The researchers compared whether diet and lifestyle interventions tailored to obesity phenotypes would work better than standard lifestyle interventions on weight loss, cardiometabolic risk factors and physical variables contributing to obesity. Cardiometabolic health describes the connection between the heart and blood vessels and the body's energy and chemical processes. It covers a wide range of disorders and risk factors that contribute to heart disease and metabolic syndrome.

In adults with obesity, the phenotype-tailored lifestyle interventions resulted in more weight loss than the standard lifestyle interventions of a reduced-calorie diet, exercise and behaviour therapy.

This 12-week, single-centre non-randomised proof-of-concept clinical trial including men and women aged 18–65 years with a body mass index (BMI) greater than 30 without history of any bariatric procedure, and current use of any medication known to affect weight. All participants completed in-person phenotype testing at baseline and after 12 weeks. Participants were assigned to their intervention based on their period of enrolment. In the first phase, participants were assigned to SLI with a low-calorie diet (LCD), moderate physical activity, and weekly behavioural therapy sessions. In the second phase, other participants were assigned to PLI according to phenotype: abnormal satiation (time-restricted volumetric LCD); abnormal postprandial satiety (LCD with pre-meal protein supplementation); emotional eating (LCD with intensive behavioural therapy); and abnormal resting energy expenditure (LCD with post-workout protein supplementation and high-intensity interval training).

The primary outcome was total body weight loss in kg at 12 weeks using multiple imputation for missing data. Linear models estimated the association of study group allocation and study endpoints adjusting for age, sex, and baseline weight.

Between July 2020 and August 2021, 211 participants were screened, and 165 were assigned to one of the two treatments in the two phases: 81 SLI (mean [SD] age 42.9 [12] years; 79% women; BMI 38.0 [6.0]) and 84 PLI (age 44.8 [12.2] years; 83% women; BMI 38.7 [6.9]); 146 completed the 12-week programmes. The weight loss was −7.4 kg (95%CI, −8.8, −6.0) with PLI vs. −4.3 kg (95%CI, −5.8, −2.7) with SLI (difference, −3.1 kg [95%CI, −5.1 to −1.1]; P = 0.004). No adverse events were reported in any group.

Overall, the findings after 12 weeks included:

  • Patients who used phenotype-tailored lifestyle interventions did better in treating their obesity than those who used standard lifestyle interventions.

  • The phenotype-focused group of patients had more significant weight loss, reduced waist circumference, reduced triglycerides, reduced daily caloric intake and less anxiety.

  • They had a substantial increase in lean mass percentage.

  • They also had a lesser decrease in the number of calories required by the body during resting conditions.

Obesity phenotypes are based on the cause of the disease and behavioural components and include three main areas:

  • Homeostatic eating - eating in response to a perceived energy need by the brain.

  • Hedonic eating behaviour – the consuming foods for pleasure, not for physical hunger or energy needs.

  • Abnormal energy expenditure – the number of calories burned in 24 hours compared to an average person.

Four actionable phenotypes of these areas include abnormal fullness, measured by calories ingested to experiencing unpleasant fullness; abnormal duration of fullness; emotional eating behaviour; and abnormal resting energy expenditure.

Acosta says more research is needed to assess the long-term effect of a phenotype-based approach. In particular, further studies may need to look at other physical and metabolic variables to understand people with no identified phenotype. He also noted that the effects of therapy on the two approaches must be examined independently. People with an emotional eating component received a more intense intervention, with 24 behaviour modification sessions, to address this underlying trait that may have a leading role in obesity development.

"More research will enhance the tailored approach proposed from the data," he added. "We will continue to work on individualised obesity therapy directed at specific traits to identify the right therapy for the right patient."

The paper, ‘ Phenotype tailored lifestyle intervention on weight loss and cardiometabolic risk factors in adults with obesity: a single-centre, non-randomised, proof-of-concept study’, was published in eClinicalMedicine. To access this paper, please click here


bottom of page