Comparison of PCOS Weight Loss Medication

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Comparison of PCOS weight loss medication

Main article: PCOS Medication

Currently experts recommend overweight women with PCOS try a low-calorie diet first to lose weight before seeking medication.

This is because for most women with PCOS, a low-calorie diet is more effective than medication alone for losing weight.

However, most studies also show that certain medications can boost the impact of a low-calorie diet (LCD) especially if tailored to the patient’s individual condition.

Fortunately, there are several types of medication, each with different properties, to suit a variety of women with PCOS, according to hyperandrogenism, insulin resistance and BMI.

In short, the following medication helps most women lose weight with PCOS:

Metformin

The insulin sensitizer metformin (Fortamet, Glucophage or Glumetza) is commonly prescribed to women with PCOS and insulin resistance (IR) struggling to lose weight via diet alone.

Together, a low-calorie diet (LCD) and metformin, often produces a more favorable outcome on testosterone levels, hirsutism, body fat, lipid profile, insulin resistance and menstrual cycles for women with PCOS and IR (Table 1).

Unfortunately, the heterogenicity of PCOS means not all women respond to metformin the same and can skew small size studies.

Nevertheless, overall metformin treatment promotes weight loss and/or maintenance among women with PCOS and IR.

StudyGambineri A, et al. (2004)Gambineri A, et al. (2006)Ganie M A, et al. (2013)Nazirudeen R, et al. (2023)
Duration6 months12 months6 months6 months
No. of women101019205627
BMI383737352632
TreatmentLCDLCD + Metformin (1700mg / day)LCDLCD + Metformin (1700mg / day)Metformin (1000mg / day)Metformin (1000mg / day)
Body weight-5.9%-7.8%-5.2%-4.3%-1.2%ns-5.0%
Waist (cm)n/an/a-3.9%-5.0%-3.3%ns-5.0%
Subcutaneous fat-8.3%ns-15.0%-16.2%-21.0%n/an/a
Visceral fat-15.2%ns-17.5%-18.4%-28.8%n/an/a
Menstruation (6 months)n/an/a3.2/64.6/65.0/6n/a
Hirsutism scoren/an/a-1.3-2.6-3.6n/a
Total testosterone (ng/ml)-0.12ns-0.65-0.1-0.15-0.32-0.42
FAI (pg/ml)n/an/a-0.6ns-2.3n/a-6.5
Androstenedione-3.9%ns+7.1%ns-20.4%-16.2%n/an/a
DHEA-S (μg/ml)-0.1ns+1.0ns+0.3ns+0.1nsn/an/a
SHBG (nmol/l)+2.5ns+2.8ns+1.5ns+2.2nsn/a+4.0ns
Insulin Sensitivity Indexn/an/a+2.0+2.5n/an/a
HOMA-IRn/an/an/an/a-1.2-2.0
LDL cholesterol (mg/dl)+6.1ns-2.9ns-8.0ns-14.0n/an/a
HDL cholesterol (mg/dl)0.0ns0.0ns+6.0+5.0n/an/a
Triglycerides (mg/dl)-2.9ns-5.2ns-1.0ns-25.0n/an/a
Table 1: Summary of low-calorie diet and or Metformin treatment results in women with PCOS. LCD, low-calorie diet; FAI, free androgen index; ns, not significant.

Flutamide

Dumesic et al. recently reported that elevated testosterone levels boosts abdominal fat deposition in PCOS women.

As a result, hyperandrogenic women with PCOS trying to lose weight (or reduce body fat) also benefit from anti-androgen medication such as Flutamide (Eulexin).

In fact, a low-calorie diet plus flutamide, produces a more favorable outcome on testosterone levels, hirsutism, body fat, lipid profile, insulin resistance and menstrual cycles among hyperandrogenic women with PCOS and IR (Table 2).

Although the heterogenicity of PCOS means not all women will respond to flutamide the same. For this reason, doctors are likely to prescribe a combined treatment plan (anti-androgen plus insulin sensitizer) to maximise patient outcomes (Table 3).

StudyGambineri A, et al. (2004)Gambineri A, et al. (2006)Amiri M, et al. (2014)
Duration6 months12 months6 months
No. of women1010191727
BMI3835373332
TreatmentLCDLCD + Flutamide (500mg/day)LCDLCD + Flutamide (500mg/day)LCD + Flutamide (500mg/day)
Body weight-5.9%-10.1%-5.2%-10.7%-8.6%
Waist (cm)n/an/a-3.9%-7.4%-7.0%
Subcutaneous fat-8.3%ns-19.8%-16.2%-31.1%n/a
Visceral fat-15.2%ns-33.0%-18.4%-44.9%n/a
Menstruation (6 months)n/an/a3.2/65.0/65.0/6
Hirsutism scoren/an/a-1.3-8.9-3.8
Total testosterone (ng/ml)-0.12ns-0.69-0.1-0.22-0.32
FAI (pg/ml)n/an/a-0.6ns-0.8n/a
Androstenedione-3.9%ns-44.0%-20.4%-41.8%n/a
DHEA-S (μg/ml)-0.1ns-0.9+0.3ns-1.4-11.5ns
SHBG (nmol/l)+2.5ns+0.5ns+1.5ns+3.0-5.5ns
QUICKI+0.03+0.01ns+0.03+0.05n/a
Insulin Sensitivity Indexn/an/a+2.0+5.1n/a
LDL cholesterol (mg/dl)+6.1ns-11.2-8.0ns-20.0-19.9
HDL cholesterol (mg/dl)0.0ns-0.7ns+6.0+7.0+3.8ns
Triglycerides (mg/dl)-2.9ns-5.8ns-1.0ns-16.0ns-3.8ns
Table 2: Summary of low-calorie diet and or Flutamide treatment results in women with PCOS. LCD, low-calorie diet; FAI, free androgen index; ns, not significant.

StudyGambineri A, et al. (2006)
Duration12 months
No. of women19201720
BMI37353335
TreatmentLCDLCD + Metformin (1700mg/day)LCD + Flutamide (500mg/day)LCD + Metformin + Flutamide
Body weight-5.2%-4.3%-10.7%-11.2%
Waist (cm)-3.9%-5.0%-7.4%-7.1%
Subcutaneous fat-16.2%-21.0%-31.1%-21.1%
Visceral fat-18.4%-28.8%-44.9%-36.1%
Menstruation (6 months)3.2/64.6/65.0/65.8/6
Hirsutism score-1.3-2.6-8.9-8.0
Total testosterone (ng/ml)-0.1-0.15-0.22-0.24
FAI (pg/ml)-0.6ns-2.3-0.8-1.6
Androstenedione-20.4%-16.2%-41.8%-33.8%
DHEA-S (μg/ml)+0.3ns+0.1ns-1.4-1.1
SHBG (nmol/l)+1.5ns+2.2ns+3.0+3.8
QUICKI+0.03+0.04+0.05+0.03
Insulin Sensitivity Index+2.0+2.5+5.1+7.8
LDL cholesterol (mg/dl)-8.0-14.0-20.0-31.0
HDL cholesterol (mg/dl)+6.0+5.0+7.0+6.0
Triglycerides (mg/dl)-1.0ns-25.0-16.0-17.0
Table 3: Summary of low-calorie diet, Metformin and Flutamide combination treatment results in women with PCOS. LCD, low-calorie diet; FAI, free androgen index; ns, not significant.

Glucagon-like Peptide-1 analogs

Glucagon-like peptide-1 (GLP-1) analogs such as Liraglutide, Exenatide and Semaglutide, mimics the effect of the body’s incretin hormone, decreasing glucose levels and suppressing appetite.

Therefore by design GLP-1 analogs are superior to Metformin for overweight women with PCOS who did not significantly lose weight after lifestyle modification.

On average GLP-1 analogs help obese women with PCOS lose approximately 5% of body weight, and improve insulin resistance, after 6 months of treatment (Table 4).

Although semaglutide (Ozempic, Wegovy, Rybelsus) treatment more than doubles the loss of weight for women with PCOS compared to Liraglutide or Exenatide.

However, Carmina and Longo did report that most severely obese (BMI >37) and or insulin resistant (HOMA-IR > 4) women with PCOS fail to respond to semaglutide treatment.

StudyElkind-Hirsch K, et al. (2008)Elkind-Hirsch K, et al. (2021)Nylander M, et al. (2017)Jensterle M, et al. (2017)Carmina E and Longo R, (2023)
Duration6 months6 months6 months3 months6 months
No. of women1420481421
BMI4037333934
TreatmentExenatide (0.2mg/day)Exenatide (2mg/weekly)Liraglutide (1.8mg/day)Liraglutide (3mg/day)Semaglutide (0.5mg/day)
Body weight-2.5%-3.4%-5.5%-5.9%-14.5%
Waist (cm)n/a-1.9%n/a-3.8%n/a
Total fat massn/a-3.8%n/an/an/a
Menstruation (6 months)3.4/6n/a5.7/6n/an/a
Total testosterone (ng/ml)-0.10ns-0.08-0.02ns-0.03nsn/a
FAI (pg/ml)-4.4-1.5-1.3n/an/a
Androstenedionen/an/a-10.9%ns+10.0%nsn/a
DHEA-S (μg/ml)+0.07ns-0.1nsn/an/an/a
SHBG (nmol/l)+2.3nsn/a+7.4+7.3n/a
HOMA-IR-1.8-0.40.0ns-0.7ns-1.0
LDL cholesterol (mg/dl)-0.6ns-2.0nsn/a+1.8nsn/a
HDL cholesterol (mg/dl)-3.2ns-1.5nsn/a-1.8nsn/a
Triglycerides (mg/dl)+14ns-10nsn/a+1.8nsn/a
Table 4: Summary of Liraglutide, Exenatide and Semaglutide treatment results in women with PCOS. FAI, free androgen index; ns, not significant.

Lastly, there is some preliminary evidence that combining GLP-1 analogs (such as Liraglutide or Exenatide) with Metformin has an added benefit on weight loss, insulin resistance and testosterone levels for some women with PCOS (Table 5).

StudyElkind-Hirsch K, et al. (2008)Jensterle M, et al. (2017)
Duration6 months3 months
No. of women14141414
BMI40413938
TreatmentExenatide (0.2mg/day)Exenatide
(0.2mg/day) + Metformin
(2000mg/day)		Liraglutide (3mg/day)Liraglutide
(1.2mg/day) +
Metformin
(1000mg/day)
Body weight-2.5%-4.2%-5.9%-3.5%
Waist (cm)n/an/a-3.8%-2.1%ns
Total fat massn/an/an/an/a
Menstruation (6 months)3.4/65.0/6n/an/a
Total testosterone (ng/ml)-0.10ns-0.18-0.03ns-0.30
FAI (pg/ml)-4.4-4.7n/an/a
Androstenedionen/an/a+10.0%ns-18.9%ns
DHEA-S (μg/ml)+0.07ns-0.03nsn/an/a
SHBG (nmol/l)+2.3ns+11.1+7.3+19.5ns
Insulin Secretion Sensitivity Index+17.9%+121%n/an/a
HOMA-IR-1.8-0.8-0.7ns-2.2
LDL cholesterol (mg/dl)-0.6ns-15.0+1.8ns-5.4
HDL cholesterol (mg/dl)-3.2ns-0.7ns-1.8ns0.0ns
Triglycerides (mg/dl)+14ns+11ns+1.8ns-3.6ns
Table 5: Summary of Liraglutide, Exenatide and Metformin combined treatment results in women with PCOS. FAI, free androgen index; ns, not significant.

Sodium–Glucose Cotransporter 2 inhibitors

Sodium–glucose cotransporter 2 (SGLT2) inhibitors such as Dapagliflozin and Empagliflozin blocks the reabsorption of glucose and sodium by the kidney and increases the loss of glucose through your urine.

As a result, SGLT2 inhibitors are a viable alternative to Metformin for the majority of women with PCOS who are trying to lose weight irrespective of insulin levels (or resistance).

On average SGLT2 inhibitors help obese women with PCOS lose approximately 1.5% of body weight, after 6 months of treatment, leading to a mild improvement in both insulin and testosterone levels (Table 6).

StudyJaved Z, et al. (2019)Elkind-Hirsch K, et al. (2021)
Duration3 months6 months
No. of women201917
BMI393738
TreatmentMetformin
(1500mg/day)		Empagliflozin
(25mg/day)		Dapagliflozin
(10mg/day)
Body weight+1.1%ns-1.4%-1.3%
Waist (cm)+0.2%ns-1.6%-2.9%
Total fat mass+3.2%-0.7%-2.4%
Total testosterone (ng/ml)-0.2ns0.0ns-0.11
FAI (pg/ml)+0.5ns-0.9ns-2.0
Androstenedione+5.6%ns0.0%nsn/a
DHEA-S (μg/ml)+0.11ns-0.03ns-0.23ns
SHBG (nmol/l)+0.0ns+1.9 n/a
HOMA-IR-0.5ns-0.2ns-0.7
LDL cholesterol (mg/dl)0.0ns-3.9ns+6.5ns
HDL cholesterol (mg/dl)-3.9ns0.0ns-1.0ns
Triglycerides (mg/dl)+3.9ns-3.9ns-11ns
Table 6: Summary of Dapagliflozin and Empagliflozin treatment results in women with PCOS. FAI, free androgen index; ns, not significant.

Finally, there is some preliminary evidence that combining SGLT2 inhibitors with GLP-1 analogs (specifically Exenatide and Dapagliflozin) has a synergist effect on women with PCOS increasing weight loss much more, than either medication alone, over the same period (Table 7).

StudyElkind-Hirsch K, et al. (2021)
Duration6 months
No. of women172020
BMI383740
TreatmentDapagliflozin
(10mg/day)		Exenatide
(2mg/weekly)		Exenatide
(2mg/weekly) + 
Dapagliflozin
(10mg/day)
Body weight-1.3%-3.4%-5.8%
Waist (cm)-2.9%-1.9%-5.4%
Total fat mass-2.4%-3.8%-8.4%
Total testosterone (ng/ml)-0.11-0.08-0.06
FAI (pg/ml)-2.0-1.5-1.5
DHEA-S (μg/ml)-0.23ns-0.10ns-0.12ns
HOMA-IR-0.7-0.4-1.7
LDL cholesterol (mg/dl)+6.5ns-2.0ns+6.0ns
HDL cholesterol (mg/dl)-1.0ns-1.5ns-1.0ns
Triglycerides (mg/dl)-11ns-10ns-30
Table 7: Summary of Dapagliflozin and Exenatide combined treatment results in women with PCOS. FAI, free androgen index; ns, not significant.

A Final Word from Fertility Science

Medication is definitely helpful for women trying to lose weight with PCOS, but results do vary a lot.

This is because PCOS is a complex disorder, with many subtypes, that no single medication corrects entirely. Hence why combined treatments usually perform better.

In short, the more personalised treatment is, the more in harmony the body is, and the quicker it burns through the kilos.

Read More:

References

Carmina E and Longo R A, (2023). Semaglutide Treatment of Excessive Body Weight in Obese PCOS Patients Unresponsive to Lifestyle Programs. https://doi.org/10.3390/jcm12185921

Dumesic D A, et al. (2022). Randomized clinical trial: effect of low-dose flutamide on abdominal adipogenic function in normal-weight women with polycystic ovary syndrome. https://doi.org/10.1016/j.fertnstert.2022.09.324

Nazirudeen R, et al. (2023). A randomized controlled trial comparing myoinositol with metformin versus metformin monotherapy in polycystic ovary syndrome. https://doi.org/10.1111/cen.14931

Elkind-Hirsch K E, et al. (2021). Exenatide, Dapagliflozin, or Phentermine/Topiramate Differentially Affect Metabolic Profiles in Polycystic Ovary Syndrome. https://doi.org/10.1210/clinem/dgab408

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

Jensterle M, et al. (2017). Short-term effectiveness of low dose liraglutide in combination with metformin versus high dose liraglutide alone in treatment of obese PCOS: randomized trial. https://doi.org/10.1186/s12902-017-0155-9

Nylander M, et al. (2017). Effects of liraglutide on ovarian dysfunction in polycystic ovary syndrome: a randomized clinical trial. https://doi.org/10.1016/j.rbmo.2017.03.023

Amiri M, et al. (2014). Effect of Metformin and Flutamide on Anthropometric Indices and Laboratory Tests in Obese/Overweight PCOS Women under Hypocaloric Diet. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227978

Ganie M A, et al. (2013). Improved Efficacy of Low-Dose Spironolactone and Metformin Combination Than Either Drug Alone in the Management of Women With Polycystic Ovary Syndrome (PCOS): A Six-Month, Open-Label Randomized Study. https://doi.org/10.1210/jc.2013-1040

Elkind-Hirsch K E, et al. (2008). Comparison of Single and Combined Treatment with Exenatide and Metformin on Menstrual Cyclicity in Overweight Women with Polycystic Ovary Syndrome. https://doi.org/10.1210/jc.2008-0115

Gambineri A, et al. (2006). Treatment with Flutamide, Metformin, and Their Combination Added to a Hypocaloric Diet in Overweight-Obese Women with Polycystic Ovary Syndrome: A Randomized, 12-Month, Placebo-Controlled Study. https://doi.org/10.1210/jc.2005-2250

Gambineri A, et al. (2004). Effect of flutamide and metformin administered alone or in combination in dieting obese women with polycystic ovary syndrome. https://doi.org/10.1111/j.1365-2265.2004.01973.x

Pasquali R, et al. (2000). Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. https://doi.org/10.1210/jcem.85.8.6738


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