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Metformin is often thought of as a diabetes drug, but that label undersells it. Because metformin lowers the body’s glucose production and improves how cells respond to insulin, it can help in several conditions where insulin resistance is part of the problem — most notably polycystic ovary syndrome (PCOS), anovulatory (lack of ovulation) infertility, and prediabetes. Researchers have also tested it for antipsychotic-related weight gain and the ability to reduce the risk of long COVID when started early in an infection. This guide breaks down what metformin is, how it works in plain language, and when it makes sense to use it, backed by high-quality evidence.
What Is Metformin? How It Lowers Blood Sugar and Boosts GLP-1
Metformin is a medication that helps your liver produce less sugar and improves your body's response to insulin. It is available in two main forms: immediate-release and extended-release.
• Immediate-release (IR): This formulation is designed to be absorbed quickly and is sold under the brand name Glucophage.
• Extended-release (ER) or Sustained-release (SR): This formulation is designed to release the medication slowly over a long period. It is available under several brand names, including Fortamet, Glucophage XR, and Glumetza.
It also acts in the gut by raising glucagon-like peptide-1 (GLP-1; a hormone made in the gut and brain) and shifting the microbiome.
Here are a few more details about how metformin works and why it matters:
• When the liver makes less sugar, you have a lower fasting glucose and less chronically high insulin levels relative to your body’s needs (hyperinsulinemia). That lowers fasting and overall blood sugar without forcing your pancreas to pump out extra insulin, which eases downstream problems tied to insulin resistance.
• On metformin, insulin sensitivity is improved, especially in the liver and gut, so glucose stays steadier with less insulin. That means steadier glucose control with a lower insulin requirement. This, in turn, may support weight-neutral or modest weight-loss trends over time.
• A raised GLP-1 nudges appetite and mealtime glucose in your favor. It does this by boosting insulin only when glucose is high, tamping down on glucagon (the hormone that is the opposite of insulin), slowing stomach emptying, and signalling fullness in the brain. This leads to smaller glucose spikes after meals and, for many, a bit less hunger.
• The change in the intestinal environment and microbiome composition increases intestinal glucose use and GLP-1 signaling, reinforcing the mealtime and appetite effects.
For all the science, see here.
Metformin Benefits Beyond Diabetes: Why It Helps with Insulin Resistance
Metformin can be used in conditions other than diabetes. At the center of PCOS, weight-related metabolic risk, and the progression from prediabetes to type 2 diabetes is insulin resistance, wherein the body needs more insulin than usual to keep its glucose in range. As noted above, metformin reduces the liver’s sugar output and improves insulin signaling, as well as works in the gut. That lowers compensatory insulin levels and eases downstream hormonal/metabolic problems. This may result in more regular menstrual cycles, better ovulation odds, and healthier metabolic markers.
Metformin for PCOS: Periods, Ovulation, and Fertility (2023 Guideline)
The most up-to-date, comprehensive reference on PCOS is the International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome 2023.
In plain language, here’s what the PCOS guidelines say about metformin:
• Metformin limitations: Metformin is not a first-line treatment for ovulation induction. The first-line medication is generally letrozole (Femara).
• Metabolic benefits: Metformin can improve insulin resistance, fasting insulin/glucose, and often lipids and weight/body mass index (BMI), especially in those with signs of insulin resistance and cardiometabolic risk.
• Menstrual regularity and ovulation: Many people see more regular cycles and a better chance of ovulation with metformin.
Bottom line for PCOS: Metformin isn’t a magic wand, but if insulin resistance is part of your picture, metformin often stabilizes cycles, supports ovulation, and improves metabolic risk. It can be a practical add-on if you can’t take (or don’t respond to) first-line fertility medications.
Metformin for Prediabetes: Who Should Take It and How Much It Helps
If you’re at high risk of type 2 diabetes, the American Diabetes Association (ADA) 2025 Standards of Care in Diabetes says to consider metformin alongside lifestyle changes. In the landmark Diabetes Prevention Program (DPP) randomized trial, metformin reduced the chance of developing diabetes by 31% over approximately 2.8 years compared with placebo (intensive lifestyle change did even better at 58%). The 10-year follow-up still showed an 18% metformin benefit overall, with bigger gains in people who started with higher blood sugar or a history of gestational diabetes.
Weight Loss on Metformin: What to Expect
But what about weight? The DPP trial showed that, on average, metformin led to modest weight loss (think: around four pounds in many people) and helped keep weight off for some. That weight change explains part of its diabetes prevention benefit.
Metformin to Prevent Antipsychotic Weight Gain (Olanzapine, Clozapine)
Some antipsychotics (such as olanzapine [Zyprexa] and clozapine [Clozaril]) can cause significant weight gain and metabolic concerns. A 2024 evidence-based guideline in Schizophrenia Bulletin concluded that metformin is the only medication with consistent evidence to prevent this early weight gain when started with the antipsychotic. Pooled data showed about nine pounds less weight gain when metformin was started with the antipsychotic vs. when the antipsychotic was prescribed alone. Lifestyle strategies can also help prevent weight gain.
Metformin and Long COVID: What the COVID-OUT Trial Found
A high-quality study, the COVID-OUT Trial, found that if people started metformin within a few days of getting COVID-19, their chances of developing long COVID were about 40% lower. The research is preliminary, but because metformin is inexpensive and widely available, it’s worth asking your clinician about it if you’re early in an infection and a good candidate.
How to Take Metformin: Dosing, Side Effects, B12, and Safety Tips
You should always follow your doctor’s prescribing instructions for any medication. That said, here are some general recommendations to consider and discuss with your doctor:
• Start low, go slow. A common plan is 500mg with a meal, increasing by 500mg each week if needed. An extended-release version of metformin may help if your stomach is sensitive.
• Take it with food. This simple step can prevent a lot of nausea/loose stools. If problems persist, ask about switching to the extended-release form of metformin.
• Check your B12 over time. If you’re taking metformin long-term, especially if you develop numbness/tingling or anemia (a condition characterized by a lack of iron in your blood), ask your clinician about a vitamin B12 test. Supplementation of B12 (injections or tablets) is sometimes necessary.
• Mind your kidneys. Make sure your kidney function is monitored during treatment. Follow your clinician’s plan around contrast scans.
Metformin FAQs: Weight Loss, Pregnancy, CT Contrast, B12
Q: Is metformin a weight-loss drug?
A: Metformin is not officially a weight-loss drug. Average weight change is small (often around four pounds), but that modest loss can still help with metabolic risk and diabetes prevention. (See the DPP trial.)
Q: Can I take it if I’m trying to get pregnant with PCOS?
A: Yes, you can take metformin if you’re trying to get pregnant with PCOS, but for ovulation induction, there are other first-line drugs you may wish to try first. Metformin can help regulate cycles and can be an adjunct or alternative when first-line options aren’t a fit. (See the 2023 PCOS guidelines.)
Q: Do I need to stop metformin for a computed tomography (CT) scan with contrast?
A: In the vast majority of cases, no, but this is individualized. Follow your radiology/primary-care team’s instructions.
Q: Does metformin lower vitamin B12? Who should get tested?
A: Be aware that long-term metformin use can lower your B12 levels; ask about periodic checks — especially if you notice neuropathy symptoms or anemia (low red blood cells). (See the ADA’s recommendations.)
Is Metformin Right for PCOS, Fertility, or Prediabetes?
Metformin’s “superpower” is straightforward: it dials down excess glucose production and improves insulin sensitivity — two levers that matter in PCOS, anovulation, and metabolic risk. The strongest non-diabetes evidence supports PCOS symptom/ovulation support (with letrozole still first-line for pregnancy) and preventing type 2 diabetes in those with high-risk prediabetes. There are targeted benefits in antipsychotic-related weight gain prevention, and early metformin use during COVID-19 lowered long-COVID risk in one high-quality study. It’s not for everything, and basics still matter, like lifestyle changes, risk-factor management, and shared decision-making. Used thoughtfully, however, metformin is a versatile and low-cost tool that can improve reproductive and metabolic outcomes for the right individuals.
Sources
• 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. (2009). The Lancet, 374(9702), 1677–1686. https://doi.org/10.1016/s0140-6736(09)61457-4
• American Diabetes Association Professional Practice Committee; 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025. Diabetes Care 1 January 2025; 48 (Supplement_1): S181–S206. https://doi.org/10.2337/dc25-S009
• Bramante, C. T., Buse, J. B., Liebovitz, D. M., et al. (2023). Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial. The Lancet, 23(10), 1119–1129. https://doi.org/10.1016/S1473-3099(23)00299-2
• Carolan, A., Hynes-Ryan, C., Mahavir Agarwal, S., et al. (2024). Metformin for the Prevention of Antipsychotic-Induced Weight Gain: Guideline Development and Consensus Validation. Schizophrenia Bulletin, 51(5), 1193–1205. https://doi.org/10.1093/schbul/sbae205
• Corcoran, C., & Jacobs, T. F. (2023, August 17). Metformin. StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK518983/
• Knowler, W. C., Barrett-Connor, E., Fowler, S. E., Hamman, R. F., Lachin, J. M., Walker, E. A., & Nathan, D. M. (2002). Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin. New England Journal of Medicine, 346(6), 393–403. https://doi.org/10.1056/nejmoa012512
• Rena, G., Hardie, D. G., & Pearson, E. R. (2017). The mechanisms of action of metformin. Diabetologia, 60(9), 1577–1585. https://doi.org/10.1007/s00125-017-4342-z
• Teede, Helena; Tay, Chau Thien; Laven, Joop S. E.; Dokras, Anuja; Moran, Lisa J; Piltonen, Terhi; et al. (2023). International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome 2023. Monash University. Online resource. https://doi.org/10.26180/24003834.v1
• What are current best practices on holding metformin prior to and post contrast administration? | Drug Information Group | University of Illinois Chicago. (n.d.). https://dig.pharmacy.uic.edu/faqs/2023-2/september-2023-faqs/what-are-current-best-practices-on-holding-metformin-prior-to-and-post-contrast-administration/
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