Table 1 Common pharmacological approaches for reducing IR in women with PCOS

Biguanides

Metformin

[153,154,155,156,157,158,159,160]

↓gluconeogenesis ↓intestinal absorption ↓lipogenesis

gastrointestinal side effects (nausea, vomiting, diarrhea)

creatinine clearance < 40 mL/min

↑glucose uptake ↑insulin receptor activity

headache

TZDs

Pioglitazone

[161, 162]

↓lipidosis ↓fatty acid release ↓disruption of insulin activity by TNF α

upper respiratory tract infection、headache、myalgia

congestive heart failure

Rosiglitazone

[163]

↑ target cell response to insulin ↑PPAR-γ transcription

peripheral edema

peripheral edema

GLP-1RAs

Liraglutide

[164, 165]

↑ glucose-dependent insulin secretion↑ lipolysis

nausea, vomiting

patients with a personal or family history of MTC

Exenatide

[166, 167]

↓ body weight↓ lipogenesis

injection site reaction

multiple endocrine neoplasia syndrome type 2

Semaglutide

[168]

↓oxidative stress ↓inflammatory response ↓Er stress

↑heart rate、hypoglycemia、headache

DPP-4 inhibitor

Sitagliptin

[169]

↓ DPP-4 enzyme

upper respiratory tract infection

angioedema

↑ incretin levels↑ insulin synthesis by pancreatic beta cells

nasopharyngitis、headache

SGLT1/2is

Dapagliflozin

[170]

↓ reabsorption of glucose from renal tubules ↓renal threshold for glucose

increased urination、Female genital mycotic infections

severe renal impairment

Empagliflozin

[171]

↓glucose toxicity and lipotoxicity ↓oxidative stress ↓inflammation

Linagliptin

[172]

↑ beta cell efficiency↑ caloric disposition ↑weight loss

Canagliflozin

[173]

↓ intestinal glucose reabsorption↑ secretion of incretin

mild diarrhea and nausea, urinary tract infection, Female genital mycotic infections

Weight loss intervention

Orlistat

[174, 175]

↓ fat absorption ↓body weight ↓ gastric and pancreatic lipases

flatulence, steatorrhea, diarrhea, increased stool frequency

acute or chronic cholecystitis

↓hydrolysis of dietary triglycerides to absorbable fatty acids

oily stool, fecal urgency

obstructive bowel disease

Bariatric surgery

[176,177,178,179]

↑endogenous secretion of incretin and GLP-1

secondary hyperparathyroidism、gastric erosion

severe heart failure、coronary artery disease、esophageal varices

↓ caloric intake by mechanically limiting food intake

Long term hypovitaminosis, increased bone fracture

stomach or esophageal ulcer、cirrhosis with portal hypertension

Supplements

Inositol

[180,181,182,183,184,185]

metabolic regulator ↑glucose uptake ↑glycogen synthesis and storage

not available

not available

Alpha-lipoic acid

[186]

anti-inflammatory, antioxidant

not available

not available

Omega-3

[187]

antioxidant、anti-inflammatory、anti-obesity ↑adiponectin

mild gastrointestinal distress, gas, nausea, diarrhea and headache

not available

Coenzyme Q10

[188,189,190]

antioxidant, ↑glucose uptake

gastrointestinal distress

not available

Vitamin E

[191, 192]

antioxidant

nausea, headache, blurred vision

not available

Probiotics

[193,194,195]

↓inflammation, regulate intestinal flora and immune responses

not available

not available

Carnitine

[196,197,198,199]

antioxidant, improves the β oxidation of fatty acids

not available

not available

TCM

Berberine

[200,201,202]

↑AMPK↑PI3K/Akt/GSK-3β↓MAPK ↓ lipogenesis ↑lipid consumption↑ antioxidase activity

gastrointestinal discomfort, constipation, mild abdominal pain, anorexia

not available

Plant polysaccharides

[203, 204]

↑serum adiponectin, antioxidant

not available

not available

Crocin

[205, 206]

anti-inflammatory; antioxidant ↑Glucose uptake

not available

not available

Hehuan Yin decoction

[207]

↑PI3K/Akt/GSK-3β

not available

not available

Acupuncture

[208,209,210,211,212]

↑GLUT4↑glucose uptake

slight bleeding at the acupuncture site

not available