Table 3.
Clinical trials of the repurposed medications for PCOS since 2016.
| Treatment (Tx) Phase/Year First Posted Ref |
Dosage (Duration of Therapy) |
Subjects Condition Groups |
Study Design | Results | Non-Serious AEs (%) (Treatment-Related) |
Serious AEs (%) (Treatment-Related) |
|---|---|---|---|---|---|---|
| Astaxanthin Not applicable/2019 [123] |
Exp: 8 mg astaxanthin + clomiphene citrate P: matching placebo + clomiphene citrate (NA) |
48 PCOS Exp = NA P = NA |
R, PA, QB | NA | NA | NA |
| Berberine Not applicable/2021 [124] |
550 mg berberine tablet, BID (before lunch and dinner) (NA) |
12 PCOS |
SGA, OL | NA | NA | NA |
| Dapagliflozin and exenatide Phase III/2019 [125] |
Exp 1: 2 mg exenatide, SC injection, once every week Exp 2: 10 mg dapagliflozin pill, PO, QD, a.m. Exp 3: 2 mg exenatide, SC injection, once every week + 10 mg dapagliflozin pill, PO, QD, a.m. Exp 4: 5 mg dapagliflozin-1000 mg glucophage pill, PO, QD, a.m. for 4 weeks after those 2 pills, PO, QD, a.m. AC: 3.75 mg phentermine-23 mg topiramate pill, PO, QD, a.m. for 2 weeks after that 7.5 mg pheniramine-46 mg topiramate pill, PO, QD, a.m. (24 weeks) |
119 PCOS, obesity Exp1 = 23 Exp2 = 23 Exp3 = 22 Exp4 = 26 AC = 25 |
R, PA, SB | NA | Yeast infection or UTI, kidney stone, nausea and upset stomach, insomnia, fatigue, headache, lightheadedness, injection site reaction, vaginal irritation, prolonged menstrual cycle, rapid heartbeat, stuffy nose | Pregnancy |
| D-chiro-inositol and myo-inositol Phase II and phase III/2017 [126] |
Exp: 500 mg myo-inositol capsule, BID (every 12 h) + 150 mg D-chiro-inositol capsule, BID (every 12 h) AC: 500 mg myo-inositol capsule, BID (every 12 h) + 13.8 mg D-chiro-inositol capsule, BID (every 12 h) (12 weeks) |
60 PCOS, infertility Exp = NA AC = NA |
R, PA, QB, controlled, multicenter | NA | NA | NA |
| Empagliflozin Phase II and phase III/2017 [127,128] |
Exp: 25 mg empagliflozin per day AC: 1500 mg metformin per day (3 months) |
40 PCOS, irregular period and biochemical hyperandrogenism Exp = 19 C = 20 |
R, PA, OL | Significant improvement in anthropometric parameters and body composition in overweight or obese women in the empagliflozin group, no change in hormonal or metabolic parameters | Headache dizziness, mild rash |
Not reported |
| Exenatide Phase IV/2017 [129,130] |
Exp1: 5 mcg or 10 mcg exenatide, BID AC: 500 mg metformin, TID or 1000 mg metformin, BID Exp2: 5 mcg or 10 mcg exenatide, BID + 500 mg metformin, TID or 1000 mg metformin, BID (12 weeks) |
183 PCOS, overweight or obesity, a disorder of glucose regulation Exp1 = 61 AC = 61 Exp2 = 61 |
R, PA, OL | Compared with metformin monotherapy, exenatide alone or in combination with metformin gives a higher remission rate in pre-diabetes PCOS women as it improves postprandial insulin secretion. | Nausea and vomiting, headache | Not reported |
| Folic acid and myo-inositol Not applicable/2022 [131] |
Exp: 200 mcg folic acid, 2 g myo-inositol, 50 mg alpha-lactalbumin, BID (6 months) |
36 PCOS, insulin resistance Exp = 36 |
R, SGA, OL | NA | NA | NA |
| Folic acid and myo-inositol Not applicable/2018 [132,133] |
Exp1: 2 mg myo-inositol, 0.2 mg folic acid, PO, BID Exp2: 2 mg myo-inositol, 0.2 mg folic acid, 50 mg alpha-lactalbumin, PO, BID (3 months) |
37 PCOS, anovulation, and infertility more than one year Exp1 = 37 Exp2 = 14 |
NR, SA, OL | Administration of myo-inositol with alpha-lactalbumin improves PCOS treatment in a patient resistant to myo-inositol | NA | NA |
| Folic acid and myo-inositol Not applicable/2018 [134] |
2000 mg myo-inositol-500 mg L-tyrosine-40 mcg chromium picolinate-55 mcg selenium-200 mcg folic acid sachet, QD (6 months) |
186 PCOS, menstrual problems, hirsutism |
SGA, OL | Improve in symptoms | NA | NA |
| Folic acid and omega-3 free fatty acid Not applicable/2017 [135,136] |
Exp: omega-3 fatty acid, 500 mg soft capsule, QD + 800 mg folic acid-70 mg selenium- 30 mg vitamin E-4 mg catechin-12 mg glycyrrhizin-30 mg Q10 coenzyme tablet, QD P: folic acid, 200 mcg capsule, BID (3 months) |
60 PCOS, infertility, micronutrient deficiency, oligomenorrhea, or complete amenorrhea for at least 90 days Exp = NA P = NA |
R, PA, DB | LH/FSH ratio, testosterone, and AMH significantly decreased in the experimental group | NA | NA |
| Folic acid, myo-inositol, and liraglutide Phase IV/2018 [137] |
AC1: dietary advice + 2 g of myo-inositol and folic acid, BID AC2: dietary advice + liraglutide starting at 0.6 mg, gradually increasing up to a dose of 3 mg per day after four weeks, pen injector (16 weeks) |
21 PCOS, obesity, metabolic syndrome AC1 = NA AC2 = NA |
R, PA, OL | NA | NA | NA |
| L-carnitine Not applicable/2018 [138] |
Exp: 50 mg clomiphene citrate tablet, PO, BID, from the third day of the cycle until the seventh day of the cycle + 1 g carnitine tablet, PO, TID, from the third day of the cycle until the day of the pregnancy test AC: 50 mg clomiphene citrate tablet, PO, BID, from the third day of the cycle until the seventh day of the cycle (14 days) |
106 PCOS Exp = 53 AC = 53 |
R, PA, DB | NA | NA | NA |
| L-carnitine Phase IV/2018 [139] |
Exp: 50 mg clomiphene citrate tablet, PO, BID, from the third day of the cycle until the seventh day of the cycle + 1 g carnitine tablet, PO, TID, from the third day until the day of the pregnancy test AC: 50 mg clomiphene citrate tablet, PO, BID, from the third day of the cycle until the seventh day of the cycle + placebo tablet, PO, TID, from the third day until the day of the pregnancy test (NA) |
150 PCOS, primary or secondary infertility Exp = NA AC = NA |
R, PA, QB | NA | NA | NA |
| Liraglutide Phase III/2018 [140] |
Exp: 0.6 mg liraglutide, SC pen injector, QD for one week, step up to 1.2 mg, SC pen injector, QD for one week, to 1.8 mg, SC pen injector, QD for one week, 2.4 mg, SC pen injector, QD for one week, to 3 mg, SC pen injector, QD final dose P: 0.6 mg placebo liraglutide, SC pen injector, QD for one week, step up to 1.2 mg, SC pen injector, QD for one week, to 1.8 mg, SC pen injector, QD for one week, 2.4 mg, SC pen injector, QD for one week, to 3 mg, SC pen injector (30 weeks) |
88 PCOS, pre-diabetes, obesity android Exp = NA P = NA |
R, PA, QB, PC | NA | NA | NA |
| N-acetyl cysteine Phase II and phase III/2016 [141] |
AC1: 1200 mg N-acetyl cysteine per day for 5 days, starting from the second day of the cycle to the sixth day of the cycle + 50 mg clomiphene citrate, PO, BID + laparoscopic ovarian drilling AC2: 50 mg clomiphene citrate, PO, BID + laparoscopic ovarian drilling (NA) |
144 PCOS, clomiphene citrate resistance, BMI between 25 and 30 kg/m2 AC1 = 60 AC2 = 60 |
R, PA, QB, PC | NA | NA | NA |
| Pioglitazone Early phase I/2016 [142] |
AC1: 2 mg cyproterone acetate-35 mcg ethinyl estradiol tablet, QD + 50 mg spironolactone, BID AC2: 500 mg metformin, TID AC3: 30 mg pioglitazone, QD (3 months) |
90 PCOS AC1 = NA AC2 = NA AC3 = NA |
R, PA, TB | NA | NA | NA |
| Pioglitazone Early Phase I/2017 [143] |
AC: 1000 mg metformin-30 mg pioglitazone tablet Exp: 500 mg metformin tablet, PO, BID (3 months) |
106 PCOS AC = 53 Exp = 53 |
R, PA, DB | NA | Not reported | Not reported |
| Pioglitazone Early Phase I/2018 [144] |
AC: 30 mg pioglitazone tablet, QD + 50 mg clomiphene citrate tablet, QD or BID (every 12 h), from the third day of menstrual cycle and continue for five days during treatment P: metformin 1500 mg, TID + clomiphene citrate 50 mg tablet, QD or BID (every 12 h), from the third day of menstrual cycle and continue for five days during treatment (3 months) |
400 PCOS and infertility AC = NA P = NA |
R, SGA, SB | NA | NA | NA |
| Resveratrol and myo-inositol Phase II/2021 [145] |
AC: 1000 mg resveratrol, BID + 1000 mg myo-inositol, BID Standard therapy group: 500 mg metformin, BID + 15 mg pioglitazone, BID (NA) |
88 PCOS, hirsutism or hyperandrogenism, oligo-ovulation or anovulation AC = 51 Standard therapy group = 51 |
R, PA, TB | NA | NA | NA |
| Sitagliptin Phase IV/2014 [146,147] |
Exp1: 100 mg sitagliptin per day, PO, for 30 days, then one placebo pill per day, PO, for 30 days Exp2: one placebo pill per day, PO, for 30 days, then 100 mg sitagliptin per day, PO, for 30 days (60 days) |
23 PCOS, BMI ≥ 30 kg/m2 Exp1 = 11 Exp2 = 12 |
R, CA, TB | ↓Maximum glucose response to oral glucose tolerance test, ↓visceral adiposity, ↑growth hormone half-life, and interval pulse |
Dizziness, headache, abdominal pain, nausea | Pancreatitis |
| Sitagliptin Phase IV/2017 [148] |
Exp1: 100 mg sitagliptin per day + lifestyle intervention Exp2: lifestyle intervention (12 weeks) |
30 PCOS, BMI ≥ 30 kg/m2 Exp1 = NA Exp2 = NA |
R, PA, OL | NA | NA | NA |
| Vitamin D Phase III/2019 [149,150] |
Exp: 6000 IU vitamin D per day, PO + 1000 mg calcium carbonate per day, PO + 1500 mg metformin per day, PO, starting with 500 mg QD for the first week, 500 mg BID in the second week, and 500 mg TID from the third week P: 1500 mg metformin per day, PO, starting with 500 mg QD for the first week, 500 mg BID in the second week, and 500 mg TID from the third week + placebo, PO (8 weeks) |
40 PCOS, Vitamin D deficiency/insufficiency Exp = 20 P = 20 |
R, PA. SB, PC | Calcium and vitamin D may support metformin effect on menstrual cycle irregularities in PCOS patients suffering vitamin D deficiency/insufficiency | Headache, gastrointestinal side effects | Not reported |
| Vitamin D Not applicable/2019 [151] |
AC: 42000 IU vitamin D per week, PO + 500 mg calcium carbonate per day P: 42000 IU vitamin D per week, PO + 500 mg calcium carbonate per day (12 weeks) |
145 PCOS = 95 Healthy = 50 AC = 55 P = 90 |
R, PA, DB, PC | NA | NA | NA |
| Vitamin D Phase IV/2019 [152] |
AC: 100,000 IU vitamin D per month, IM + 1000 mg metformin tablet, BID + 50 mg clomiphene citrate tablet, BID, from the second day to the sixth day of the cycle, starting from the third month to the fifth month P: 1000 mg metformin tablet, BID + 50 mg clomiphene citrate tablet, BID, from the second day to the sixth day of the cycle, starting from the third month to the fifth month (5 months) |
120 PCOS, vitamin D deficiency, infertility, clomiphene resistance AC = 60 P = 60 |
R, PA, OL | NA | NA | NA |
Abbreviations: a.m.: before noon; AC: active comparator; AEs: adverse effects; AMH: anti-mullerian hormone; BID: twice a day; BMI: body mass index; CA: crossover assignment; DB: double-blind; Exp: experimental; FSH: follicle stimulation hormone; g: gram; IM: intramuscular; IU: international unit; LH: luteinizing hormone; mcg: microgram; mg: milligram; NA: not available; OL: open-label; P: placebo; PA: parallel assignment; PC: placebo-controlled; PCOS: polycystic ovary syndrome; PO: per oral (by mouth); QB: quadruple blind; QD: once a day; R: randomized; Ref: reference; SB: single-blind; SC: subcutaneous; SGA: single group assignment; TB: triple blind; TID: three times a day; Tx: treatment; UTI: urinary tract infection.