Liraglutide Plus Keto Diet Boosts Weight Loss in Obesity

TOPLINE:

Compared with a very low-calorie ketogenic diet (VLCKD) alone, combining a VLCKD with liraglutide led to greater weight loss and metabolic improvements over 4 months in adults with obesity.

METHODOLOGY:

• VLCKD induces weight loss by enhancing satiety through sustained ghrelin suppression and minimizes muscle loss, but because long-term dietary adherence is challenging, researchers investigated whether combining a protein-rich VLCKD with the GLP-1 receptor agonist liraglutide could synergistically suppress appetite via both ghrelin-dependent and -independent pathways.
• They conducted an observational, real-world study to compare the weight-loss effects, metabolic effects, and safety of a VLCKD alone with the same diet combined with liraglutide in adults with obesity (BMI > 30) over 4 months.
• The VLCKD-alone group (n = 20; mean age, 51.3 years; 85% women) followed an approximately 800 kcal/d diet consisting of four or five ketogenic meal replacements, along with two servings of low-glycemic index vegetables, every day for at least 45 days. Meal replacements were then gradually replaced by protein-based dishes, and caloric intake was progressively increased to about 1200 kcal/d.
• The VLCKD plus liraglutide group (n = 20; mean age, 49.3 years; 75% women) followed the same diet and additionally received liraglutide, starting at 0.6 mg/d and gradually increased to a maximum of 1.8 mg/d as tolerated by the participants.
• Various parameters, including weight, BMI, waist circumference, lipid profile, markers of glucose metabolism, renal function, and liver function, were measured at baseline and after 4 months.

TAKEAWAY:

• At 4 months, the VLCKD plus liraglutide group achieved greater weight loss than the VLCKD-alone group (-20.8 kg vs -14.5 kg; P for time × group interaction = .013 ), with a larger proportion achieving at least 15% weight loss (95% vs 65%; P = .048).
• All participants in the VLCKD plus liraglutide group achieved sustained ketosis (beta-hydroxybutyrate level > 0.5 mmol/L) compared with 80% in the VLCKD-alone group (P = .035).
• The VLCKD plus liraglutide group also showed a greater reduction in BMI (P for time × group interaction = .027), along with significantly greater improvements in insulin sensitivity and homeostatic model assessment of insulin resistance (P for time × group interaction ≤ .001 for both).
• No symptomatic hypoglycemia or significant adverse changes in renal or liver function were reported, but the VLCKD plus liraglutide group experienced higher rates of nausea or vomiting (100% vs 0%) and constipation (80% vs 35%) than the VLCKD-alone group.

IN PRACTICE:

“Despite both liraglutide and VLCKD approaches being at risk of underuse in the current therapeutic landscape, our results suggest that their combination represents a highly cost-effective and clinically valuable strategy for obesity management,” the authors of the study wrote. “These findings are particularly timely, as liraglutide is approaching patent expiration and will likely become significantly more affordable,” they added.

SOURCE:

This study, led by Elisabetta Camajani, PhD, Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele, Rome, Italy, was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

This study’s limitations included its small sample size and the lack of long-term follow-up data. The nonrandomized, pragmatic design, where participants chose their own interventions, may have introduced selection bias. Body composition analyses were not conducted, preventing assessments of muscle vs fat loss.

DISCLOSURES:

No disclosures or funding source was provided for this study.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.