Effects of Dichrostachys glomerata and Cissus quadrangularis Extracts on GLP-1 Secretion and DPP-4 Activity in Overweight and Obese Individuals: A Randomized Controlled Trial

Background: and Objectives: Dichrostachys glomerata and Cissus quadrangularis, two species traditionally used in Cameroon, are recognized for their weight-reducing potential. This study examined the effects of standardized extracts of these botanicals on glucagon-like peptide-1 (GLP-1), dipeptidyl peptidase-4 (DPP-4), and key metabolic outcomes in individuals with excess body weight. Materials and Methods: In this 16-week, randomized, double-blind, placebo-controlled trial, 248 adults (126 women and 122 men; mean age 41.3 ± 0.3 years; BMI 25–34.9 kg/m²) were assigned to receive 400 mg D. glomerata extract (DGE), 300 mg C. quadrangularis extract (CQE), semaglutide (dose-escalated from 3 mg to 14 mg), or placebo, administered once daily. Primary assessments included changes in GLP-1 levels and DPP-4 activity. Secondary evaluations included body composition, caloric intake, satiety response, fasting glucose levels, and lipid profiles. Results: Participants receiving DGE or CQE displayed notable elevations in circulating GLP-1 (+38.6 pg/mL and +42.2 pg/mL, respectively; p < 0.01) and significant reductions in DPP-4 activity (−15.3% and −17.8%; p < 0.01) compared with placebo. Both extracts produced substantial improvements in body weight (−5.2% and −5.8%), body fat (−10.3% and −10.9%), energy intake (−16.2% and −17.5%), and satiety (+25.6% and +27.4%) (p < 0.01). Significant changes in fasting glucose and serum lipid levels were also observed (p < 0.05). These responses are similar to those of semaglutide. Moreover, GLP-1 increments showed strong negative correlations with body fat percentage (r = −0.91 to −0.92; p < 0.001) and DPP-4 activity (r = −0.97 to −0.98; p < 0.001). Conclusion: Supplementation with D. glomerata and C. quadrangularis extracts enhanced GLP-1 secretion and reduced DPP-4 activity, yielding significant benefits for body composition and metabolic parameters. These findings indicate that both botanicals are promising natural agents for managing obesity through incretin-based mechanisms.