Carbimazole and methimazole: what the studies show

Carbimazole only works once your body has turned it into methimazole. So a trial of either drug tells you about both, and the evidence below mixes them freely. We picked the studies guidelines lean on most. For each: what kind of study, who took part, and the numbers the authors reported.

Key points

• Length matters, up to a point: 12 months beats 6, and very long low-dose treatment cut relapse to 15% in one trial.
• Lower starting doses are safer: agranulocytosis was about four times more common at 30 mg than 15 mg of methimazole.
• Methimazole beats PTU for speed of control and liver safety, except in the first trimester of pregnancy.
• Tablets relapse more often than radioactive iodine or surgery, but radioiodine can worsen eye disease.

How long to treat

Cochrane review of dose, regimen and duration (2010)

Systematic review of 26 randomised trials, 3,388 people with Graves’ disease. Using the titration approach, 12 months of treatment was better than 6 months, with no benefit from going beyond 18 months. Block and replace and titration had similar relapse rates (51% and 54%), but block and replace caused more rashes (10% vs 6%) and more people stopped because of side effects (16% vs 9%). The reviewers rated the overall trial quality as poor.

Long-term low-dose methimazole (Azizi et al., 2019)

Randomised trial, Iran, 258 people with a first episode of Graves’ disease. After 18 to 24 months of methimazole, people either stopped or continued low-dose treatment for a total of 5 to 10 years. Four years after stopping, hyperthyroidism had returned in 15% of the long-term group against 53% of the conventional group. No new drug reactions appeared after the first 18 months. This trial is the main evidence behind offering long-term low-dose treatment as an alternative to radioiodine or surgery.

Dose and the blood risk

Methimazole vs PTU and two methimazole doses (Nakamura et al., 2007)

Randomised trial, four Japanese hospitals, 240 newly diagnosed patients. By 12 weeks, methimazole 30 mg a day had normalised free T4 in 96.5% of patients, compared with 78.3% on PTU 300 mg and 86.2% on methimazole 15 mg. The authors concluded that 15 mg suits mild and moderate disease, 30 mg suits severe disease, and PTU is not recommended for first use.

Starting dose and agranulocytosis (Takata et al., 2009)

Retrospective comparison, one Japanese hospital, 4,826 patients. When the hospital changed its usual starting dose, agranulocytosis fell from 0.814% of 2,087 patients on 30 mg a day to 0.219% of 2,739 patients on 15 mg a day. The authors recommended 15 mg as the usual starting dose.

754 cases of agranulocytosis (Nakamura et al., 2013)

Case series over 30 years, Japan. 84.5% of cases began within 90 days of starting treatment, often abruptly after a recent normal count. The estimated incidence was 0.1% to 0.15% of treated patients. Reviewing 30 deaths, the authors judged that some might have been prevented, and stressed telling every patient about the warning signs. This is why the advice is to stop and get a blood count at the first sore throat or fever.

Pregnancy

Danish nationwide birth cohort (Andersen et al., 2013)

Register study, 817,093 children born 1996 to 2008. Birth defects diagnosed by age two were found in 9.1% of children exposed to methimazole or carbimazole in early pregnancy, 8.0% with PTU, and 5.7% in children not exposed. Both drug groups were associated with birth defects, but the types of defect differed between them.

Korean nationwide cohort (Seo et al., 2018)

Insurance database study, 2.9 million pregnancies, 2008 to 2014. Malformations were found in 7.27% of babies exposed to antithyroid drugs in the first trimester, against 5.94% of those not exposed, with the higher risk seen mainly with methimazole. Higher cumulative doses carried more risk. Together with the Danish study, this underpins the advice to use effective contraception, plan pregnancy with the specialist, and favour PTU in the first trimester.

Liver safety: PTU vs methimazole

US adverse event reports (Rivkees and Szarfman, 2010)

Analysis of over 40 years of FDA adverse event reports. Severe liver injury was reported far more often than expected with PTU in children and adolescents, but not with methimazole, whose strongest signal was mild cholestatic liver injury in people over 60. PTU also showed a vasculitis signal in young people. The US PTU label now carries a boxed warning about severe liver injury.

Tablets vs radioactive iodine vs surgery

Network meta-analysis (Sundaresh et al., 2013)

Eight comparative studies, 1,402 adults, average follow-up about five years. Relapse was 52.7% after antithyroid drugs, 15% after radioactive iodine and 10% after surgery. Across 31 cohort studies, 13% of people had side effects from the drugs: skin problems were more common with methimazole and liver problems with PTU. The authors rated the evidence as moderate to high risk of bias.

Swedish randomised trial (Törring et al., 1996)

179 people with Graves’ disease, at least four years of follow-up. Relapse was 42% (age 20 to 34) and 34% (age 35 to 55) after 18 months of tablets, 21% after radioiodine, and 3% to 8% after surgery. All three normalised hormone levels within about six weeks, and 90% of patients in every group were satisfied. High TSH receptor antibodies at the end of tablet treatment predicted relapse.

Radioiodine and eye disease (Bartalena et al., 1998)

Randomised trial, Italy, 443 people with mild or no eye disease. Eye disease appeared or worsened in 15% of people after radioiodine (persisting in 5%), against 3% on 18 months of methimazole. Adding a three-month course of prednisone after radioiodine prevented progression. This is why antithyroid tablets are preferred when eye disease is active.

Carbimazole and methimazole: equal strength

Bioavailability study (Jansson et al., 1983)

Seven volunteers. 15 mg of carbimazole produced the same methimazole blood levels as 9.2 mg of methimazole, the same number of molecules. Peak levels came about 0.9 hours after either tablet, and the half-life was 5.4 to 5.7 hours. The authors concluded that carbimazole is fully converted and the two are equipotent on a molar basis. That is the basis for the usual 10 mg carbimazole to 6 mg methimazole conversion. Both are sold as plain tablets: carbimazole and methimazole through PockDose, carbimazole also through Yasabai and VGR Australia.

What the guidelines conclude

In 2018 the European Thyroid Association put this evidence into a guideline. Its default for an adult with new Graves’ disease: methimazole (carbimazole, in countries like the UK) for 12 to 18 months. Children get 24 to 36 months. TSH receptor antibodies are measured before stopping, because high levels point to relapse. Anyone planning a pregnancy moves to PTU and stays on it through the first trimester. If the disease comes back after a full course, the guideline points to radioiodine or surgery, but it accepts long-term low-dose methimazole as an option, which is where the Azizi trial fits. See how the options compare.

Studies summarised on this page

Abstracts checked through Europe PMC on 15 October 2026. Each summary reports the authors' own figures.

1. Antithyroid drug regimen for treating Graves' hyperthyroidism (Abraham et al., 2010) — Cochrane Database of Systematic Reviews
2. Increased remission rates after long-term methimazole therapy in Graves' disease (Azizi et al., 2019) — Thyroid
3. Comparison of methimazole and propylthiouracil in Graves' disease (Nakamura et al., 2007) — Journal of Clinical Endocrinology & Metabolism
4. Methimazole-induced agranulocytosis is more frequent with 30 mg than 15 mg daily (Takata et al., 2009) — Thyroid
5. Analysis of 754 cases of antithyroid drug-induced agranulocytosis in Japan (Nakamura et al., 2013) — Journal of Clinical Endocrinology & Metabolism
6. Birth defects after early pregnancy use of antithyroid drugs, a Danish nationwide study (Andersen et al., 2013) — Journal of Clinical Endocrinology & Metabolism
7. Antithyroid drugs and congenital malformations, a nationwide Korean cohort study (Seo et al., 2018) — Annals of Internal Medicine
8. Dissimilar hepatotoxicity profiles of propylthiouracil and methimazole in children (Rivkees and Szarfman, 2010) — Journal of Clinical Endocrinology & Metabolism
9. Comparative effectiveness of therapies for Graves' hyperthyroidism (Sundaresh et al., 2013) — Journal of Clinical Endocrinology & Metabolism
10. Graves' hyperthyroidism: antithyroid drugs, surgery or radioiodine (Törring et al., 1996) — Journal of Clinical Endocrinology & Metabolism
11. Therapy for hyperthyroidism and the course of Graves' ophthalmopathy (Bartalena et al., 1998) — New England Journal of Medicine
12. Comparative bioavailability of carbimazole and methimazole (Jansson et al., 1983) — Int J Clin Pharmacol Ther Toxicol