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PCOS, diabetes and metabolic syndrome

Recognizing insulin resistance, diabetes and fatty liver early

Metabolism is an important part of polycystic ovary syndrome. Since 2026, the syndrome has had a new international name: PMOS, Polyendocrine Metabolic Ovarian Syndrome. The name begins with the word “polyendocrine”. PCOS is first of all a hormonal disorder that involves the brain, the ovaries and the adrenal glands. The word “metabolic” shows that this hormonal disorder also affects the sugar and fat metabolism of the whole body.

Many metabolic changes start early and cause no symptoms for a long time. A woman can feel healthy while diabetes or a fatty liver develops over the years. An early assessment is therefore one of the most important measures in PCOS.

What is insulin resistance?

Insulin allows sugar to move from the blood into the cells. In insulin resistance, the cells respond less well to insulin. At first the body makes up for this: it produces more insulin. Blood sugar then stays normal for a long time, but the high insulin level acts on many organs. It increases the production of androgens in the ovaries, disturbs ovulation and promotes the storage of fat in the belly and in the liver.

Insulin resistance is common in PCOS and does not depend on weight alone. In a study using the most accurate method of measurement, about 75% of slim women with PCOS had insulin resistance, and almost all women with a higher weight. A higher weight makes insulin resistance worse, but it is not its only cause.

What comes first: androgens or insulin?

Insulin and androgens reinforce each other. A high insulin level increases the production of androgens in the ovaries. Androgens, in turn, also reduce insulin sensitivity. They increase belly fat, change the way fat tissue works and weaken the response of the muscles to insulin. Research has not fully shown which change starts first.

How high is the risk of diabetes?

Women with PCOS have about a three times higher risk of impaired glucose tolerance and type 2 diabetes than women without the syndrome. Diabetes also often appears earlier in them, sometimes as early as the age of 30 or 40. The risk is highest with a higher weight, but it also exists with a normal weight. Ethnic background plays a role as well. Women of Asian background, for example, have a higher risk even at a lower weight.

A 2025 study from the UK Biobank compared women with PCOS with women of the same age and the same weight. Even at the same weight, the risk of type 2 diabetes was about 50% higher in PCOS. The syndrome itself is therefore a risk factor of its own.

Which test is right?

The guideline recommends a blood sugar assessment in all women with PCOS at diagnosis, regardless of age and weight. The most accurate method is the oral glucose tolerance test, in which blood sugar is measured in the fasting state and two hours after a sugar drink. Fasting blood sugar and the long-term sugar value HbA1c are simpler, but they miss some women with impaired glucose tolerance.

Measuring insulin resistance itself is not simple. The most accurate method is used only in research. In daily practice, prognostic metabolic and hormonal markers often show the course of insulin resistance, for example SHBG, androgens, triglycerides, HDL cholesterol and waist circumference. For this reason, the time-consuming glucose tolerance test is not always needed.

After that, the doctor repeats the test every one to three years, depending on the risk. The risk is higher with a higher weight, previous raised blood sugar values, a history of gestational diabetes, diabetes in the family, high blood pressure and certain ethnic backgrounds. Before pregnancy and before fertility treatment, a glucose tolerance test is especially important.

A visible sign of insulin resistance is a dark, velvety discoloration of the skin on the neck, in the armpits or in the groin (acanthosis nigricans). This sign is a reason for a careful metabolic assessment.

What about diabetes in pregnancy?

Women with PCOS have a clearly higher risk of diabetes in pregnancy. Gestational diabetes increases the risks for the mother, such as pre-eclampsia and cesarean section, and for the child, such as a low or high birth weight, difficulties during birth and low blood sugar after birth. It is at the same time a warning sign of type 2 diabetes later in life. For this reason, the woman needs regular check-ups after birth. The guideline also recommends a glucose tolerance test before pregnancy or at the first antenatal visit, and a further test at 24 to 28 weeks.

What is metabolic syndrome?

Metabolic syndrome describes the combination of several risk factors: extra belly fat, raised blood pressure, raised triglycerides, low HDL cholesterol and raised blood sugar. A review from 2019 shows that metabolic syndrome is about twice as common in women with PCOS as in other women. Each of these factors increases the risk of heart and blood vessel disease, and together they reinforce each other. More in the article “PCOS and the heart”.

What about fatty liver?

A fatty liver linked to metabolism (today called MASLD) is more common in PCOS. Insulin resistance and androgens both play an important role. A high insulin level promotes the storage of fat in the liver, and androgens increase fat in the belly and in the liver. A 2023 meta-analysis of 36 studies with about 5,000 women with PCOS found fatty liver in about 40% of women. In the UK Biobank study, about 36% of women with PCOS had a fatty liver on MRI, compared with about 24% of women of the same weight without the syndrome. In both studies, women with raised androgens were affected more.

A fatty liver causes no symptoms for a long time. It can, however, lead to inflammation and scarring of the liver and raises the risk of diabetes. Fatty liver does not affect only the liver. People with MASLD die more often from disease of the heart and blood vessels than from liver disease. A 2021 meta-analysis of 36 studies with about 5.8 million people showed that fatty liver raises the risk of heart attack, stroke and other cardiovascular events by about 45%. When the disease has progressed to fibrosis, the risk is about 2.5 times higher. More in the article “PCOS and the heart”.

Why does each form have a different prognosis?

The risk of metabolic disorders differs between the forms of the syndrome. Women with raised androgens and an irregular cycle, the so-called classic phenotypes, usually have the highest risk. Women without raised androgens have a lower risk on average, but they still have a risk. This difference supports the central role of androgens. Determining the phenotype therefore helps to plan the tests and the treatment correctly for each woman.

How is it treated?

Lifestyle is the basis. A balanced diet and regular exercise improve insulin sensitivity, even without weight loss. With a higher weight, a loss of just 5-10% clearly lowers the risk of diabetes.

Is metformin right for every woman?

For many years, almost every woman with PCOS received metformin. The reasoning was simple: if there is insulin resistance, the medicine helps everyone. The data do not support this generalization.

The 2023 international guideline does not recommend metformin for all women with PCOS. It recommends considering it mainly in adult women with a body mass index of 25 kg/m² or more, for weight and metabolism. Randomized trials show a moderate effect on weight, insulin and blood lipids. In women with a normal weight, the metabolic benefit is usually small.

The strongest data on preventing diabetes do not come from PCOS. The large DPP study included people with prediabetes and a higher weight. Metformin lowered the risk of diabetes by 31%, and lifestyle changes lowered it by 58%. In PCOS, there are no large randomized trials over several years that show that metformin prevents diabetes. Most trials in PCOS last less than one year.

Metformin also has side effects. Stomach and bowel complaints, such as nausea and diarrhea, are common. Long-term use can lead to a lack of vitamin B12.

Metformin therefore has a place, but not for every woman. The doctor uses it when there is a clear reason: a higher weight with metabolic disorders, prediabetes, or marked insulin resistance that does not improve with lifestyle changes. For inositol, the 2023 guideline still considers the data insufficient and calls it an experimental treatment.

What do GLP-1 receptor agonists offer?

GLP-1 receptor agonists, such as liraglutide and semaglutide, copy a hormone of the gut. They reduce appetite, slow down stomach emptying and increase insulin release only when blood sugar is high. Tirzepatide also acts on the receptor of a second gut hormone, GIP. The 2023 international guideline states that these medicines can be considered in adult women with PCOS and a higher weight, always together with lifestyle changes.

In PCOS, the data come from small randomized trials. In the largest trial with liraglutide 3 mg, 82 women with PCOS and obesity received the medicine or placebo for 32 weeks. Weight fell by 5.7% with liraglutide and by 1.4% with placebo. The free androgen index also fell. Stomach and bowel complaints occurred in 58% of women on liraglutide and 19% on placebo. A 2025 meta-analysis of randomized trials showed that GLP-1 receptor agonists lower weight, body mass index and insulin resistance more than metformin and placebo. The authors stress, however, that studies on the long-term effect on blood sugar and blood lipids are still needed. A second 2025 meta-analysis also found more regular periods.

The strongest data on diabetes risk come from large trials in people with obesity, not specifically with PCOS. In the STEP trials, after 68 weeks of semaglutide 2.4 mg, 84% of people with prediabetes had normal blood sugar again, compared with 48% on placebo. In the SURMOUNT-1 trial, 1,032 people with obesity and prediabetes received tirzepatide or placebo for three years. Type 2 diabetes developed in 1.3% on tirzepatide and in 13.3% on placebo. About half of this effect was due to weight loss. For comparison, in the DPP study metformin lowered the risk of diabetes by 31%. In PCOS, there is still no study over several years with diabetes as the outcome.

These medicines also have limits. When treatment stops, the weight usually comes back. In the STEP 4 trial, people who stopped semaglutide regained 6.9% of their body weight within 48 weeks. In women with PCOS who continued metformin, about one third of the lost weight had returned two years after stopping semaglutide, and the improvements in blood sugar and blood lipids had moved back towards the starting values. In addition, there are no safety data in pregnancy. The woman needs reliable contraception and stops the medicine before trying to become pregnant. With tirzepatide, the pill may be absorbed less well, so an additional method of contraception is needed.

GLP-1 receptor agonists act mainly on weight and metabolism. They lower androgens to some degree, but on their own they do not treat the hormonal disorder of the syndrome. For this reason, they have a place in women with a higher weight and metabolic disorders, as part of a comprehensive treatment plan and not as a solution on their own.

How does hormonal treatment fit in?

The choice of hormonal treatment also takes metabolism into account. Different pills have different effects on blood sugar and blood lipids. In women with a high metabolic risk, the doctor therefore chooses the combined pill with particular care.

Is the risk lifelong?

Symptoms of the cycle and the skin often become weaker after the menopause. The risk of diabetes, fatty liver and heart disease, however, remains and continues to rise with age. Metabolic follow-up therefore does not end with the wish for a child or with the menopause.

The practice's approach

Sources: International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome (Monash University, ESHRE, ASRM, 2023); Teede HJ et al., Human Reproduction 2023. European Society of Endocrinology – The polycystic ovary syndrome: a position statement (Conway G et al., European Journal of Endocrinology 2014). Kakoly NS et al., Ethnicity, obesity and the prevalence of impaired glucose tolerance and type 2 diabetes in PCOS, Human Reproduction Update 2018. Stepto NK et al., Human Reproduction 2013 (insulin resistance in slim women). Lim SS et al., Metabolic syndrome in polycystic ovary syndrome, Obesity Reviews 2019. Henney AE et al., Risk of type 2 diabetes, MASLD and cardiovascular disease in people living with polycystic ovary syndrome, Journal of Clinical Endocrinology and Metabolism 2025. Manzano-Nunez R et al., Non-alcoholic fatty liver disease in patients with polycystic ovary syndrome: a systematic review, meta-analysis, and meta-regression, Journal of Clinical Medicine 2023. Mantovani A et al., Non-alcoholic fatty liver disease and risk of fatal and non-fatal cardiovascular events: an updated systematic review and meta-analysis, The Lancet Gastroenterology & Hepatology 2021. Elkind-Hirsch KE et al., Liraglutide 3 mg on weight, body composition, and hormonal and metabolic parameters in women with obesity and polycystic ovary syndrome: a randomized placebo-controlled phase 3 study, Fertility and Sterility 2022. Lin S et al., Efficacy and safety of GLP-1 receptor agonists on weight management and metabolic parameters in PCOS women: a meta-analysis of randomized controlled trials, Scientific Reports 2025. Sridharan K, Sivaramakrishnan G, Glucagon-like peptide-1 receptor agonists and sodium glucose transporter-2 inhibitors in polycystic ovarian syndrome: systematic review and network meta-analysis of randomized clinical trials, Diabetology & Metabolic Syndrome 2025. Perreault L et al., Changes in glucose metabolism and glycemic status with once-weekly subcutaneous semaglutide 2.4 mg among participants with prediabetes in the STEP program, Diabetes Care 2022. Rubino D et al., Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial, JAMA 2021. Jastreboff AM et al., Tirzepatide for obesity treatment and diabetes prevention, New England Journal of Medicine 2025. Jensterle M, Ferjan S, Janez A, The maintenance of long-term weight loss after semaglutide withdrawal in obese women with PCOS treated with metformin: a 2-year observational study, Frontiers in Endocrinology 2024. Knowler WC et al. (Diabetes Prevention Program Research Group), Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin, New England Journal of Medicine 2002.