Exenatide, dapagliflozin or phentermine/topiramate differentially affect metabolic profiles in polycystic ovary syndrome
Main article: Getting Pregnant with PCOS
There is currently a number of anti-diabetic medications available that can simultaneously assist with weight loss and improve insulin resistance.
Liraglutide and exenatide are two Glucagon-like peptide-1 type agonists (GLP-1RA) which have been proven to assist with weight loss in women with PCOS and improve their insulin resistance, however they are not without any drawbacks, mainly administration by injection and gastrointestinal side effects.
A new class of anti-diabetic medication, sodium–glucose cotransporter 2 inhibitors (SGLT2i), has been shown to exert similar effects, in a number of small studies of women without PCOS, with the advantage of being able to take orally.
However studies of SGLT2i in women with PCOS have been limited to date, with a previous study showing improvements in anthropometric and body composition but not in hormonal or metabolic parameters.
For this reason further studies are required to confirm the findings and establish whether this new class of anti-diabetic medication is more effective than existing medication for women with PCOS.
To evaluate and compare the efficacy of GLP-1RA and SGLT2i type medication, alone and combined, in obese non-diabetic women with PCOS.
Initially a total of 130 nondiabetic obese (BMI >30) women with PCOS enrolled in this study. PCOS was defined according to the modified National Institutes of Health criteria (1990).
Women diagnosed with diabetes, pregnant or trying to conceive, using oral or hormonal contraceptive, steroid hormones, anti-obesity drugs or drugs that effect gastrointestinal motility / carbohydrate metabolism and currently smoking were automatically excluded from the study to minimize potential bias.
Following assessment against the inclusion / exclusion criteria, 119 women were then randomized into 5 treatment groups.
- Group 1: Exenatide (EQW)
- Group 2: Dapagliflozin (DAPA)
- Group 3: Exenatide and Dapagliflozin (EQW/DAPA)
- Group 4: Dapagliflozin and Metformin (DAPA/MET)
- Group 5: Phentermine topiramate extended release (PHEN/TPM)
A variety of clinical, laboratory, anthropometric and physical measurements were carried out pre-trial, mid-trial and post-trial, to thoroughly record any changes, with any adverse events documented via a questionnaire.
All participants received the same diet and exercise advice over the 24 week trial.
A total of 27 women failed to complete the trial with medication side effects (n=10), noncompliance (n=5) and pregnancy (n=4) the main reasons.
Final treatment group sizes were;
- Group 1 = 20
- Group 2 = 17
- Group 3 = 20
- Group 4 = 19
- Group 5 = 16
Baseline pre-trial characteristics of the various mean glycemic, hormonal, cardiometabolic, anthropometric and DXA indices showed no statistically significant differences between the groups.
Following treatment fasting (FMG) and mean glucose (MBG) levels, also known as blood sugar levels improved significantly in all treatment groups, with EQW/DAPA treatment showing the greatest drop in MBG.
Similarly fasting insulin sensitivity improved significantly in all groups although only EQW and EQW/DAPA showed a significant increase in carbohydrate metabolism (mean IS-SI) confirming GLP-1 agonists positive effects on beta cell function.
Absolute body weight and BMI also decreased significantly in all treatment groups with EQW/DAPA (-6.9%) and PHEN/TPM (-8.0%) treatment showing the biggest weight loss among the 5 treatment options. Unsurprisingly this translated into significantly reduced abdominal adiposity (mean waist circumference and waist to height ratio) and body fat composition (total body fat mass and percentage).
|Body weight (%)||-6.9||-8.0|
|Waist circumference (cm)||-6.0||-7.0|
|Total body fat mass (kg)||-4.1||-5.4|
|Total body fat (%)||-1.8||-2.2|
Hormonal analysis showed that levels of total testosterone and DHEA-S decreased significantly in almost all treatment groups, with PHEN/TPM treatment having no effect on DHEA-S levels. Overall DAPA, followed by EQW and EQW/DAPA had the greatest effect on hormone parameters.
|Total testosterone (ng/dL)||-8.2||-6.4||-11.0|
|Free Androgen Index||-1.5||-1.5||-2.0|
Interestingly no effect on cholesterol levels was seen from any of the treatments, although blood pressure (systolic and diastolic) was improved by all treatments with EQW and EQW/DAPA treatment groups showing the most improvement.
Adverse event analysis showed that gastrointestinal events were the most commonly reported side effects among all participants. Nausea and injection site reactions where the most common adverse event in the EQW treatment group, while DAPA treatment increased the rate of urinary and genital tract infections for users in line with previous trial reports. A significantly higher number of unpleasant side effects reported using PHEN/TPM treatment resulted in a high dropout rate for this group.
SUMMARY: PCOS WEIGHT LOSS MEDICATION
In this study, comparing weight loss medication in obese women with PCOS, the combination of Exenatide and Dapagliflozin was superior to either Exenatide or Dapagliflozin on its own after 24 weeks, resulting in significantly greater weight loss, reduction in body fat and waist circumference.
- No placebo control group.
- Small treatment group sizes.
- Some tests were not of gold-standard accuracy, namely total testosterone and insulin sensitivity.
No external funding was declared for this study.
Excessive abdominal fat around the stomach and abdomen.
Proportional measurements of the human body.
Cells that produce, store and release insulin.
Dual-energy X-ray absorptiometry (scan).
Javed Z, et al. (2019). Effects of empagliflozin on metabolic parameters in polycystic ovary syndrome: A randomized controlled study. https://doi.org/10.1111/cen.13968
Jabbour S A, et al. (2018). Effects of exenatide once weekly plus dapagliflozin, exenatide once weekly, or dapagliflozin, added to metformin monotherapy, on body weight, systolic blood pressure, and triglycerides in patients with type 2 diabetes in the DURATION-8 study. https://doi.org/10.1111/dom.13206
Pereira M J, et al. (2018). A Randomized Controlled Trial of Dapagliflozin Plus Once-Weekly Exenatide Versus Placebo in Individuals with Obesity and Without Diabetes: Metabolic Effects and Markers Associated with Bodyweight Loss. https://doi.org/10.1007/s13300-018-0449-6
Frías J P, et al. (2016). Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial. https://doi.org/10.1016/s2213-8587(16)30267-4
Vilsbøll T, et al. (2012). Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. https://doi.org/10.1136/bmj.d7771
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