Cissus Quadrangularis (CQR-300®) and Dichrostachys Glomerata (Dyglomera®) Extracts Increase GLP-1 Levels and Inhibit Dipeptidyl Phosphate-4 Activity in Healthy Overweight and Obese Adults
Phase: PHASE1
Conditions: Obesity and Overweight, Appetite Regulation
Sponsor: University of Yaounde 1

STUDY 
PROTOCOL: 
DICHROSTACHYS 
GLOMERATA 
AND 
CISSUS 
QUADRANGULARIS EXTRACTS INCREASE GLP-1 LEVELS IN PATIENTS 
WITH OVERWEIGHT AND OBESITY: A RANDOMISED CONTROLLED TRIAL 
 
General information 
NCT Number: NCT06827002 
Protocol title: Effect of Standardised Cissus Quadrangularis and Dichrostachys Glomerata 
Extracts on GLP-1 Concentration and DPP-4 Activity in Healthy Adults who are Overweight 
and or Obese 
Date: 11/02/2025 
Funder: J & A Oben Foundation, Entree Kameni Damas, Yaounde, Cameroon 
Project summary 
Obesity is a growing global health crisis, currently affecting over 2.3 billion individuals 
worldwide. This study aims to evaluate the comparative effects of standardised Cissus 
quadrangularis extract (CQE) and Dichrostachys glomerata extract (DGE) on obesity-related 
metabolic parameters, with a specific focus on glucagon-like peptide-1 (GLP-1) levels and 
dipeptidyl peptidase-4 (DPP-4) enzyme activity in adults who are overweight/obese. In this 
12-week clinical trial, participants will receive either standardised Cissus quadrangularis 
extract (CQE), Dichrostachys glomerata extract (DGE), or placebo. Key outcomes assessed 
include GLP-1 levels, DPP-4 activity, food intake, body weight, blood lipid profiles, fasting 
blood glucose, and visceral fat mass, measured at baseline and at designated intervals. This 
clinical study is informed by prior preclinical research involving 18 adult male Wistar rats 
(150–200 g), randomly divided into three groups: a control group on a normal diet, and two 
treatment groups receiving either DGE (400 mg/kg) or CQE (300 mg/kg) alongside a normal 
diet. Results showed that both extracts significantly increased GLP-1 levels and inhibited 
DPP-4 activity compared to the control group. These effects were associated with reductions 
in food intake, body weight, and fasting glucose levels, as well as favourable changes in lipid 
profiles, including HDL, LDL, and triglycerides. The findings suggest that Cissus 
quadrangularis extract (CQE) and Dichrostachys glomerata extract (DGE) may exert 
anti-obesity effects through mechanisms involving GLP-1 enhancement and DPP-4 
inhibition. This clinical study is designed to provide human evidence supporting the potential 

of these plant extracts as alternative therapies for weight management and metabolic health 
improvement. 
 
 
 
Investigators and Roles 
●​ Janvier Youovop1,3-  write the original draft, develop and execute the methodology, 
formally analyse the data, review and edit the manuscript 
●​ Guy Takuissu2,3-  write the original draft, develop and execute the methodology, 
review and edit the manuscript 
●​ Régine Minoue3-  develop and execute the methodology, review and edit the 
manuscript 
●​ Felix Nwang3- develop and execute the methodology, review and edit the manuscript 
●​ Maryam Adeboyega3-  write the original draft, formally analyse the data, review and 
edit the manuscript 
●​ Crista Arrey4-  develop and execute the methodology, review and edit the manuscript 
●​  Inelle Makamwe1- formally analyse the data, review and edit the manuscript 
●​ Julius Oben1,3*- conceptualised and will supervise the study,  review and edit the 
manuscript 
Affiliations 
●​
1 Laboratory of Nutrition and Nutritional Biochemistry, Department of Biochemistry, 
University of Yaounde 1, Yaounde, Cameroon; 
●​
2Centre for Food, Food Security and Nutrition Research (CRASAN), Institute for 
Medical Research and Medicinal Plant Studies (IMPM), Ministry of Scientific 
Research and Innovation, Yaoundé, Cameroon; 
●​
3Cameroon Nutrition and Dietetic Research Centre, Research and Development 
Department, J&A Oben Foundation, Yaoundé, Cameroon; 
●​
4National Obesity Centre, Yaounde, Central Hospital, Cameroon. 
 
Rationale & background information 
Obesity is a health burden affecting over 2.3 billion people of all ages globally [1]. 
The development and progression of obesity involve a complex pathogenesis, and several 
drugs have been developed to target these pathways. In recent years, dipeptidyl peptidase-4 

(DPP-4) inhibitors or gliptins, such as sitagliptin, saxagliptin, and vildagliptin, have been 
considered viable obesity management options. Gliptins inhibit DPP-4, an enzyme known to 
deactivate the glucagon-like peptide-1 (GLP-1) hormone, contributing to the development 
and progression of obesity and other metabolic diseases. GLP-1 is an important incretin 
hormone secreted in the L-cells of the gut for the maintenance of blood sugar homeostasis. It 
has other pleiotropic effects through its receptors in the liver, brain, and stomach to delay 
gastric emptying, reduce appetite, and induce significant weight loss [2]. In healthy 
individuals, GLP-1 has a half-life of >2 minutes due to the activities of DPP-4 [3]. Some 
studies have reported increased DPP-4 levels in people with obesity [4], further reducing the 
incretin effects of GLP-1. Gliptins are primarily invented to manage type 2 diabetes. 
However, their weight loss effects are quite significant, suggesting their potential as a weight 
loss management option. 
Synthetic drugs used for obesity management are often associated with side effects 
and contraindications. For conditions such as obesity, patients with obesity often require 
individualised management options owing to sensitivity and the high likelihood of 
comorbidities. For example, patients with obesity are more vulnerable to pancreatitis and 
pancreatic cancer [5], whereas gliptins are associated with a high incidence of acute 
pancreatitis.6 In terms of cost, gliptins are considerably expensive [7]. The current 
FDA-approved gliptins are intended for the management of diabetes. The off-label use of 
gliptins for obesity management may lead to increased demand, higher prices, and potential 
shortages. Therefore, there is a need to explore safe, cost-effective, and potent alternatives for 
obesity management. 
Owing to their potency and low toxicity, natural products continue to emerge as 
potential drug leads for several metabolic disease conditions. Dichrostachys glomerata is a 
popular Cameroonian spice, and Cissus quadrangularis is an ornamental and medicinal plant 
that grows in Africa and Asia and has shown tremendous effects on weight loss. Youovop et 
al. [8] reported that Dichrostachys glomerata extract (DGE) induced 22.85% weight loss in 
60 subjects at 12 weeks. In a double-blind, placebo-controlled study involving 35 subjects, 
Cissus quadrangularis extract (CQE) reduced body fat by 12.8% in 8 weeks [9]. The 
mechanisms by which these two extracts exert their weight loss effects are not fully 
understood. It has been suggested that DGE and CQE may exert weight loss effects through 
anorectic mechanisms. Studies by Kim et al. [10] and Lee et al. [11] proposed that DGE and 

CQE may reduce food intake through increased adiponectin secretion and the AMPK 
pathway. To date, no study has investigated the effects of DGE or CQE on GLP-1 levels or 
DPP-4 activity. Hence, this study aims to evaluate the effects of DGE and CQE on blood 
GLP-1 levels and the enzyme dipeptidyl peptidase-4 (DPP-4) in healthy patients who are 
overweight and/or obese as potent alternatives in the management of obesity. 
References  
●​ WHO. 
Obesity 
and 
Overweight, 
<https://wwwwhoint/news-room/fact-sheets/detail/obesity-and-overweight> (2021). 
●​ van Bloemendaal, L., Ten Kulve, J. S., la Fleur, S. E., Ijzerman, R. G. & Diamant, M. 
Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS. J 
Endocrinol 221, T1–16 (2014). https://doi.org/10.1530/JOE-13-0414 
●​ Ahren, B. & Schmitz, O. GLP-1 receptor agonists and DPP-4 inhibitors in the 
treatment 
of 
type 
2 
diabetes. Horm Metab Res 36, 867–876 (2004). 
https://doi.org/10.1055/s-2004-826178 
●​ Valerio, C. M. et al. Dipeptidyl peptidase-4 levels are increased and partially related 
to body fat distribution in patients with familial partial lipodystrophy type 2. Diabetol 
Metab Syndr 9, 26 (2017). https://doi.org/10.1186/s13098-017-0226-0 
●​ Yadav, D. & Lowenfels, A. B. The epidemiology of pancreatitis and pancreatic 
cancer. 
Gastroenterology 
144, 
1252–1261 
(2013). 
https://doi.org/10.1053/j.gastro.2013.01.068 
●​ Tkac, I. & Raz, I. Combined Analysis of Three Large Interventional Trials With 
Gliptins Indicates Increased Incidence of Acute Pancreatitis in Patients With Type 2 
Diabetes. Diabetes Care 40, 284–286 (2017). https://doi.org/10.2337/dc15-1707 
●​ Filipova, E. P., Uzunova, K. H. & Vekov, T. Y. Comparative analysis of therapeutic 
efficiency and costs (experience in Bulgaria) of oral antidiabetic therapies based on 
glitazones 
and 
gliptins. 
Diabetol 
Metab 
Syndr 
7, 
63 
(2015). 
https://doi.org/10.1186/s13098-015-0059-7 
●​ Youovop, J., Takuissu, G., Mbopda, C., Nwang, F., Ntentié, R., Mbong, M., Azantsa, 
B., Singh, H. & Oben, .J. The effects of DGE (Dichrostachys glomerata extract) on 
body fat percentage and body weight: a randomized, double-blind, placebo-controlled 
clinical trial. Functional Foods in Health and Disease 13, 334–346 (2023). 
https://doi.org/10.31989/ffhd.v13i6.1088 

●​ Nash, R., Azantsa, B., Kuate, D., Singh, H. & Oben, J. The Use of a Stem and Leaf 
Aqueous Extract of Cissus quadrangularis (CQR-300) to Reduce Body Fat and Other 
Components of Metabolic Syndrome in Overweight Participants. J Altern 
Complement Med 25, 98–106 (2019). https://doi.org/10.1089/acm.2018.0016 
●​ Kim, H. L., Lee, S. K., Min, D. E., Choi, B. K. & Lee, D. R. Anti-Obesity Effect of 
Dyglomera((R)) Is Associated with Activation of the AMPK Signaling Pathway in 
3T3-L1 Adipocytes and Mice with High-Fat Diet-Induced Obesity. Molecules 27 
(2022). https://doi.org/10.3390/molecules27103288 
●​ Lee, H. J., Le, B., Lee, D. R., Choi, B. K. & Yang, S. H. Cissus quadrangularis extract 
(CQR-300) inhibits lipid accumulation by downregulating adipogenesis and 
lipogenesis 
in 
3T3-L1 
cells. 
Toxicol 
Rep 
5, 
608–614 
(2018). 
https://doi.org/10.1016/j.toxrep.2018.02.008 
 
Study Goal 
The primary goal of this study is to evaluate the efficacy of the standardised extract from two 
Cameroonian spices, Dichrostachys glomerata (DGE) and Cissus quadrangularis (CQE), as 
potential safe, cost-effective, and potent alternatives for enhancing GLP-1 production for the 
management of obesity. 
Specific Objectives 
1.​ To evaluate the effect of DGE and CQE on circulating GLP-1 levels in overweight or 
obese individuals. 
2.​ To assess the impact of DGE and CQE on DPP-4 activity. 
3.​ To determine the effect of DGE and CQE on cardiometabolic parameters and the 
extent of weight loss achieved through supplementation over the study period. 
Study design 
This is a double-blind, placebo-controlled clinical trial. 
Inclusion Criteria: Healthy males and non-pregnant, non-lactating females aged 18–65 years 
with a BMI between 25–34 kg/m². 
Exclusion Criteria: Age <18 or >65 years, morbid obesity (BMI >34.9 kg/m²), 
insulin-dependent diabetes, pregnancy or breastfeeding, active infections, systemic diseases 
(e.g., HIV/AIDS, hepatitis, malignancy within 5 years), or use of medications/natural 
products that may interfere with study parameters. 
Randomisation and Blinding 

Participants will be randomised using a random number generator. Treatments (DGE, CQE, 
or placebo) will be packaged in identical opaque containers, sequentially numbered according 
to the randomisation sequence. Allocation concealment is maintained, with investigators and 
participants blinded to treatment assignments. 
Methodology 
Test Material 
Standardised Cissus quadrangularis extract (CQE) and Dichrostachys glomerata 
extract (DGE) are procured from Gateway Health Alliances, Fairfield, California, USA, as 
400 mg and 300 mg capsules, respectively. Identical placebo capsules containing 400 mg of 
dextrin are also procured. Oral semaglutide (Rybelsus®) was purchased and then repackaged 
into capsules identical to CQE, DGE and placebo capsules. 
Intervention 
Participants will receive capsules of either DGE (400 mg), CQE (300 mg), 
semaglutide (4-week dose escalation from 3 to 7 to 14mg) or placebo (400 mg dextrin) daily 
for 12 weeks. The size and shape are made so that neither the researcher nor the participant 
would distinguish the capsules. Patients are instructed to maintain their usual lifestyle and 
dietary habits and to report any delays in taking the capsules. Patients are monitored for 
adverse effects throughout the study.  
Dietary and exercise restrictions 
No dietary or exercise restrictions are recommended for patients. Patients are 
encouraged to continue their normal lifestyle routine. 
Primary efficacy endpoint evaluation 
Anthropometric parameters: body weight, height, and body fat percentage 
Height is measured at the screening visit (visit 1). Body weight and body mass index 
(BMI, kg/m2) are measured at baseline, week 4, week 8, and week 12. The body fat 
percentage (%) is measured using an impedance meter at the same time points. 
Metabolic parameters 
Blood samples are collected after a 12-hour fast at baseline, week 4, week 8, and 
week 12 to assess fasting blood glucose levels, blood lipid levels, GLP-1 levels and DPP-4 

activity. Glucose levels are measured using the glucose oxidase‒peroxidase enzymatic 
method with a touch glucometer. Blood lipid levels (cholesterol, triglyceride, and HDL-c) are 
assessed using commercial kits. LDL-c is assessed using the Friedewald et al. formula [12]. 
GLP-1 levels are determined using the Ray Bio® GLP-1 ELISA kit. DPP-4 activity is 
assessed with Cayman’s DPP-4 inhibitor screening kit according to the manufacturer’s 
instructions, and activity is expressed as a percentage relative to the positive control using the 
following formula:  
 
% remaining activity = (slope of test sample/slope of positive control) × 100 
 
Secondary efficacy endpoint evaluation: Energy intake 
 ​
Food intake and calorie content are monitored via a self-reported 7-day food diary. 
The FAO Food Composition Table for Cameroon is used to estimate carbohydrate, lipid, and 
protein intake. Energy intake (EI) is calculated using the following formula: 
EI (Kcal/day) = Ecarb + Elip + E prot 
With: 
Ecarb/prot (Kcal/day) = (Amount of carb/prot ingested (g) × 4 kcal)/7 
Elip(Kcal/day) = (Amount of lip ingested (g) × 9 kcal)/7 
Considering that: 1 g carbohydrate or protein = 4 kcal and 1 g lipid = 9 kcal 
Statistical analysis 
All variables were expressed as a means ± standard error of the mean. The normality 
of the data is confirmed by the Kolmogorov-Smirnov test and Q-Q plots. The statistical 
analysis is conducted using the Statistical Package for Social Sciences (SPSS v.24, Inc. 
Chicago, IL, USA). The ANOVA with post hoc Tukey test is used for descriptive and 
comparative analysis. The Pearson correlation is used to assess the association between 
GLP-1, DPP-4, body fat, and energy intake. The significance is set at p ≤ 0.05. 
Expected outcomes of the study 
1.​ Scientific and Clinical Impact 
This study will advance the understanding through which  Dichrostachys glomerata (DGE) 
and Cissus quadrangularis (CQE) exert anti-obesity effects, especially their influence on the 
GLP-1/DPP-4 pathway. It will potentially expand safer and effective therapeutic options for 
obesity, particularly for patients with comorbidities and contraindications to synthetic drugs. 

2.​ Economic Impact 
Pharmacological discovery with natural products such as Dichrostachys glomerata and Cissus 
quadrangularis could encourage local economies through cultivation, processing, and 
commercialisation. It will also encourage investment in functional foods or supplements 
derived from African biodiversity, increasing global visibility of African plant-based health 
solutions. 
Duration of the project: 12 weeks 
Ethics 
The project aligns with the International Conference on Harmonisation Guidelines for Good 
Clinical Practice (ICH GCP) and the Declaration of Helsinki and is registered on 
clinicaltrials.gov (NCT06827002)on 02/11/2025. This study protocol and the informed 
consent form are also approved by the University of Yaounde I Joint Institutional Review 
Board for Animal & Human Bioethics (JIRB) under number BTC-JIRB2023-084. Written 
informed consent from patients is also obtained by the principal investigator after the study's 
nature, scope, and expected results are explained. 
Informed consent forms 
The informed consent form is uploaded on figshare with DOI 10.6084/m9.figshare.29294219 
Funding 
Funding is provided by the Cameroon Nutrition and Dietetic Research Centre, Research and 
Development Department of the J&A Oben Foundation (Grant ID: JAOF122025).