Obesity and Overweight, Appetite Regulation
Conditions
Keywords
Natural Products, GLP-1, DDP-4 Inhibitors, Obesity management, Appetite regulation, CQR-300®, Dyglomera®
Brief summary
Obesity is a global health crisis affecting over 2.3 billion individuals worldwide. This prospective study aims to evaluate the comparative effects of standardised Cissus quadrangularis extract (CQE) and Dichrostachys glomerata extract (DGE) on obesity-related parameters, focusing on their impact on glucagon-like peptide-1 (GLP-1) levels and dipeptidyl peptidase-4 (DPP-4) enzyme activity in obese subjects. Parameters such as GLP-1 levels, DPP-4 activity, food intake, satiety, body weight, blood lipids, fasting blood glucose, and visceral fat mass will be measured at baseline and various intervals. In our previous pre-clinical trial involving 18 adult male Wistar rats (150-200 g), randomly divided into three groups: a control group fed a normal diet, and two treatment groups receiving DGE (400 mg/kg) or CQE (300 mg/kg) alongside a normal diet, the results demonstrated that both DGE and CQE significantly increased GLP-1 levels and inhibited DPP-4 activity compared to the control group. These effects were associated with reduced food intake, body weight, and fasting blood glucose levels. Additionally, both extracts positively modified blood lipid profiles, with significant changes in HDL, LDL, and triglyceride levels. The findings suggest that DGE and CQE exert their anti-obesity effects through mechanisms involving GLP-1 enhancement and DPP-4 inhibition, offering potential therapeutic pathways for weight management and metabolic health. This prospective study aims to provide clinical evidence supporting the use of these plant extracts in addressing obesity and its related complications.
Detailed description
Obesity is a health burden affecting over 2.3 billion people of all ages globally. 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 as a viable obesity management option. Gliptins inhibit DPP-4, an enzyme known to deactivate the GLP-1 hormone, contributing to the development and progression of obesity and other metabolic diseases. GLP-1 is one of the important incretin hormones secreted in the L-cells of the gut for the maintenance of blood sugar homeostasis. It exhibits other pleiotropic effects through its receptors in the liver, brain, and stomach to delay gastric emptying, reduce appetite, and induce significant weight loss. In healthy individuals, GLP-1 has a half-life of \>2 minutes due to the activities of DPP-4 . Some studies have observed higher DPP-4 levels in obese individuals, 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, presenting as a potent management option for obesity. Synthetically produced drugs are often associated with side effects and contraindications. For conditions such as obesity, patients often require unique management options due to sensitivity and the high likelihood of comorbidities. For instance, obese individuals are more vulnerable to pancreatitis and pancreatic cancer, whereas gliptins are associated with a high incidence of acute pancreatitis. Gliptins also present other side effects such as upper respiratory infections, headache, urinary tract infections, arthralgia, and in severe cases, Stevens-Johnson syndrome. Cost-wise, gliptins are considerably expensive. The current FDA-approved gliptins are intended for the management of diabetes. Prescribing them for obesity may lead to higher demand and prices as well as scarcity. Hence, there is a need for a wider range of safe, cost-effective, and potent alternatives. Natural products continue to emerge as potential drug leads for several metabolic disease conditions due to their potency and low toxicity. DGE (Dichrostachys glomerata), a popular Cameroonian spice, and CQE (Cissus quadrangularis), an ornamental and medicinal plant growing in Africa and Asia, have shown tremendous effects on weight loss. A recent study showed that DGE induced 22.85% weight loss in 60 subjects in 12 weeks. In a double-blind placebo-controlled study involving 35 subjects, CQE reduced body fat by 12.8% in 8 weeks. The mechanism of these two extracts is not fully understood. It has been proposed that DGE and CQE are anorectic. Some studies suggested that DGE and CQE reduced food intake through increased adiponectin secretion and the AMPK pathway. Additionally, CQE was shown to boost serotonin levels. Serotonin has received much attention in weight loss research in the past. It has been implicated for its appetite-suppressing effect on the arcuate nucleus hypothalamus, a region responsible for food intake and energy expenditure. Up to the present, no study has investigated the effect of DGE or CQE on GLP-1 or DPP-4 levels. Hence, this study aims to evaluate the efficacy of DGE and CQE as potent alternatives to gliptins in obesity management.
Interventions
DRUGDichrostachys glomerata
DGE were procured from Gateway Health Alliances, Fairfield in 400 mg and 300 mg capsules.
DRUGCissus quadrangularia
CQR-300® were procured from Gateway Health Alliances, Fairfield in 400 mg and 300 mg capsules.
DRUGDextrin
Placebo capsules containing 400 mg of dextrin, looking identical to DGE and CQE were also procured from Gateway Health Alliances, Fairfield, California, USA.
Oral semaglutide (Rybelsus®) was purchased and then repackaged into capsules looking identical to DGE, CQE and placebo capsules.
Sponsors
University of Yaounde 1
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
The study involves Two hundred and forty eight (248) overweight or obese participants (25 ≥ BMI ≤ 34), randomly divided into four groups: the placebo, DGE group, CQE and semaglutide groups.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Healthy males and non-pregnant/non-lactating females * Participants aged 18 to 65 years old * Participants with BMI between 25 and 34 kg/m² * Participants willing to comply with the study protocol
Exclusion criteria
* Participants younger than 18 years or older than 65 years * Participants not available for the study period * Morbid obesity (BMI \> 34.9 kg/m²) * Diabetes mellitus requiring daily insulin management * Pregnancy or breastfeeding * Active infection * Systemic diseases, including HIV/AIDS, Active hepatitis, Clinical signs of active malignancy within the past 5 years * Use of any medication or natural health product that might affect the parameters of interest in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of DGE and CQE on participants GLP-1 level | Baseline (Week 0), Week 4, Week 8, Week 12 and Week 16 | Description: GLP-1 levels will be determined in pg/mL using the RayBio® GLP-1 ELISA kit. |
| Effect of DGE and CQE on participants DPP4 activity | Baseline (Week 0), Week 4, Week 8, Week 12 and Week 16 | DPP-4 activity will be measured using Cayman's DPP-4 inhibitor screening assay kit according to the manufacturer's instructions. Unit of Measure: % Activity Remaining This will be determined using the calculation below: % activity remaining = (slope of test sample/positive control slope) × 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of DGE and CQE on participants' energy Intake | Week 16 | Participants will maintain a food diary for seven consecutive days (the last week of each study period), recording all foods, drinks, and snacks consumed. Food intake will be recorded in household measurements and converted into grams using manufacturer labels where applicable. Nutrient intake (carbohydrates, lipids, and proteins) will then be quantified in grams using the FAO food composition table for Cameroon. Energy intake will be calculated as follows: EI (Kcal/day) = ECarb + ELip + EProt where: ECarb(Kcal/day)=Amount of carb ingested (g) x 4 Kcal/7 Eprot (Kcal/day)=Amount of carb/prot ingested (g) x 4 Kcal/7 ELip (Kcal/day)=Amount of lipid ingested (g) x 9 Kcal/7 Considering that: 1 g carbohydrate or protein = 4 Kcal and 1 g lipid = 9 kcal |
| Effect of DGE and CQE on participants Fasting blood glucose | Baseline (Week 0), Week 4, Week 8, Week 12 and Week 16 | Glucose levels will be measured in blood samples taken from each participant after a 12-hour fast at Baseline (Week 0), Week 4, Week 8, Week 12 and Week 16 using the glucose oxidase-peroxidase enzymatic method with a OneTouch Ultra 2 glucometer. Unit of measure: mg/dL |
| Effect of DGE and CQE on participants BMI | Baseline (Week 0), Week 4, Week 8, Week 12 and Week 16 | BMI will then be calculated as follows: BMI (kg/m²)=Weight in Kg/Height in meter² |
| Effect of DGEand CQE on participants Body weight | Baseline (Week 0), Week 4, Week 8, Week 12 and Week 16 | Body weight will be measured in Kg using a TANITA brand scale at Visits (baseline (Week 0), Week 4, Week 8, Week 12 and Week 16) |
| Effect of DGE and CQE on participants Body Fat percentage | Baseline (Week 0), Week 4, Week 8, Week 12 and Week 16 | The body fat percentage (%) was measured using an impedance meter at baseline (Week 0), Week 4, Week 8, Week 12 and Week 16 |
| Effect of DGE and CQE on participants Lipid Profile | Baseline (Week 0), Week 4, Week 8, Week 12 and Week 16 | Blood lipid levels (cholesterol, triglycerides, and HDL-c) will be measured in blood samples taken from each participant after a 12-hour fast at baseline (Week 0), Week 4, Week 8, Week 12 and Week 16 using ChronoLab commercial kits according to the protocol of the manufacturers. LDL-c will be assessed using the Friedewald et al. formula. LDL-c = Plasma-c - HDL-c - Total Plasma triglyceride/5 Unit of measure: mg/dL |
Countries
Cameroon
Contacts
PRINCIPAL_INVESTIGATORJulius E Oben, PhD
University of Yaounde 1
Outcome results
None listed