GLP-1 RAs facilitate maintenance of healthy weight and lifestyle, offer cardiometabolic benefits
21 Feb 2025
byDr. Cheryl Yuen-Ching Chan, Specialist in Family Medicine, Hong Kong
In an interview with MIMS Doctor, Dr Cheryl Yuen-Ching Chan, Specialist in Family Medicine in Hong Kong, discussed the importance of obesity management, as well as the role of primary care physicians and use of glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), such as liraglutide, in helping patients achieve and maintain target body weight, thereby empowering them to develop and maintain a healthy lifestyle. She also shared a case illustrating sustained weight reduction with liraglutide in a patient with obesity where lifestyle modification had been inadequate.
Urgency of managing obesity in primary care
“In primary care, we see many patients with diabetes, hypertension, hyperlipidaemia, gout, and other cardiovascular-kidney-metabolic [CKM] syndrome conditions,” noted Chan. “The majority of these patients are overweight, have obesity or normal-weight central obesity.”
“Obstructive sleep apnoea, knee osteoarthritis, gastroesophageal reflux disease, fatty liver, hernia in men, urinary incontinence in women, depression, anxiety, and social impairment are other common obesity-associated conditions. The severity of these conditions appears to increase with increased duration of obesity,” she added.
“Weight management is a lifelong battle that requires regular follow-up to ensure patients do not regain the weight they have lost. A wholistic approach that encompasses preventive or additional measures throughout life is necessary to reduce CKM risks and prevent serious obesity-related conditions, such as a stroke 30 years in the future, as patients age or as their lifestyle changes,” highlighted Chan.
“Primary care doctors, as patients’ first point of contact, play an important role in multidisciplinary weight management and prevention of interlinked obesity-related complications. We should provide comprehensive care and continuity of care, as well as coordinate care with other healthcare providers [eg, dietitians] and secondary and tertiary care when needed,” said Chan.
Yoyo dieting
Willpower, diet and exercise alone are often inadequate in providing sufficient weight reduction in the long term, with over 80 percent of individuals eventually regaining the weight they lost. This weight cycling is often referred to as yoyo dieting. [Obesity and Set-Point Theory, StatPearls Publishing, January 2024; N Engl J Med 2011;365:1597-1604; Front Genet 2019;10:1015]
Yoyo dieting could be attributed in part to genetic or epigenetic factors, modern-world obesogenic environment, stress-eating, unsustainable lifestyle changes or unrealistic goals and expectations. The set-point theory suggests that the human body has a predetermined weight or fat mass set point range. Various compensatory physiological mechanisms maintain that set point, while feedback systems drive the body weight back towards it, which may also explain the high incidence of weight regain.
Liraglutide for weight reduction and maintenance
“When diet, exercise and lifestyle modification fail, I discuss other adjunctive therapies with patients, and let them participate in shared decision-making,” said Chan. “Some may not like the side effects of certain oral medications, such as oily stool with orlistat, or insomnia with phentermine, while others may have an aversion to needles.”
“As shown in the case report, liraglutide was preferred by the patient who did not have needle-phobia and found the once-daily administration convenient. It was also beneficial for her prediabetes and may be beneficial for her fatty liver,” said Chan.
Liraglutide is an acylated human GLP-1 analogue (GLP-1 is a physiological regulator of appetite and food intake) that binds to and activates the GLP-1 receptor. It regulates appetite by increasing feelings of fullness and satiety while lowering feelings of hunger and prospective food consumption, leading to reduced food intake. Weight loss with liraglutide is achieved mainly through loss of fat mass, with relatively greater reduction in visceral fat than subcutaneous fat. However, it does not increase energy expenditure compared with placebo. [Saxenda Prescribing Information, 2022]
The 56-week, double-blind SCALE Obesity and Prediabetes trial, which included 3,731 patients with body mass index (BMI) ≥30 kg/m2 or ≥27 kg/m2 plus treated or untreated dyslipidaemia or hypertension, found that liraglutide 3 mg QD, as an adjunct to diet and exercise, was associated with significant body weight reduction as long as patients continued treatment. Liraglutide treatment was also associated with reductions in cardiometabolic risk factors, including waist circumference, blood pressure, blood glucose (more pronounced in patients with prediabetes, such as our patient case, than in those with normoglycaemia) and inflammatory markers, as well as modest improvements in fasting lipid levels. Liraglutide use for 3 years was associated with a 79 percent risk reduction vs placebo in onset of type 2 diabetes (hazard ratio [HR], 0.21; 95 percent confidence interval [CI], 0.13–0.34). (Figure 1) [N Engl J Med 2015;373:11-22; Lancet 2017;389:1399-1409]
Cardiovascular (CV) safety and benefit of liraglutide were further demonstrated in the LEADER trial in 9,340 patients with median follow-up of 3.8 years. Results showed that the rate of first occurrence of death from CV causes, nonfatal MI, or nonfatal stroke among patients with type 2 diabetes was lower with liraglutide vs placebo (13.0 vs 14.9 percent; HR, 0.87; 95 percent CI, 0.78–0.97; pnoninferiority<0.001; psuperiority=0.01), and fewer patients in the liraglutide vs placebo group died from CV causes (4.7 vs 6.0 percent; HR, 0.78; 95 percent CI, 0.66–0.93; p=0.007). [N Engl J Med 2016;375:311-322]
Conclusion
“Obesity is a very common chronic problem with many short- and long-term health consequences, imposing a huge burden on the healthcare system. Primary care doctors, who are patients’ first point of contact, should consider the biopsychosocial aspects and involve patients in setting sustainable short- and long-term goals for weight reduction,” Chan concluded.
