Thiazolidinediones (TZDs): How They Work, Types, Doses, Side Effects and Who Should Avoid Them
Updated: 6 days ago
Written and medically reviewed by Dr. Baraa Alnahhal, MD · Last reviewed: October 2026 · How we review
Quick Answer: What are thiazolidinediones?
Thiazolidinediones (TZDs, or glitazones) are oral tablets for type 2 diabetes that help the body use insulin more efficiently by activating PPAR-gamma receptors in fat, muscle and liver cells. Pioglitazone and rosiglitazone are the two types, taken once daily. Common effects are swelling and weight gain; they can raise the risk of heart failure, fractures and liver damage. [1][2]
What the research says
Pioglitazone lowered heart attack, stroke and death risk, but raised heart failure. A meta-analysis of 19 randomized trials (16,390 patients) found death, heart attack or stroke in 4.4% of people on pioglitazone vs 5.7% on control (hazard ratio 0.82); serious heart failure was 2.3% vs 1.8%. (Lincoff et al., JAMA, 2007) [3]
Long-term TZD use roughly doubled fracture risk in women. Across 10 randomized trials (13,715 participants), TZDs raised overall fracture risk (odds ratio 1.45); in women the odds ratio was 2.23, with no significant rise in men. (Loke et al., CMAJ, 2009) [4]
Pioglitazone cut repeat stroke or heart attack in insulin-resistant people without diabetes. In a trial of 3,876 people after a stroke or mini-stroke, the outcome occurred in 9.0% on pioglitazone vs 11.8% on placebo over 4.8 years; weight gain, swelling and fractures were more common. (Kernan et al., N Engl J Med, 2016) [5]
Key takeaways
Thiazolidinediones treat type 2 diabetes by making cells respond better to insulin. [1]
There are two types: pioglitazone (Actos) and rosiglitazone (Avandia). [1]
They are taken as a tablet, usually once a day, and can be combined with metformin or sulfonylureas; pioglitazone can also be used with insulin, but rosiglitazone with insulin is not recommended. [1]
The most common side effects are swelling in the legs and ankles and weight gain. [1]
They are not suitable during pregnancy and may not be suitable with heart failure, liver disease, kidney disease or bladder cancer. [1]
What are thiazolidinediones?
Thiazolidinediones are a class of medicines that treat type 2 diabetes by improving insulin sensitivity, lowering blood sugar and helping reduce fat stored in the liver. [1]
You may also hear them called TZDs or glitazones. Both names mean the same group of drugs.
They come as tablets you swallow, typically once per day. [1]
What else are thiazolidinediones used for?
Thiazolidinediones are also used off-label for polycystic ovary syndrome, now also called polyendocrine metabolic ovarian syndrome (PMOS). [1]
"Off-label" means a doctor prescribes a medicine for a use outside its main approved purpose.
They may also help with scarring of the liver (cirrhosis) in people who have metabolic dysfunction-associated steatotic liver disease (MASLD). [1]
How do thiazolidinediones work?
They act on PPAR-gamma (PPAR-γ) receptors in your fat, muscle and liver cells. These receptors help control metabolism. [1]
Here is what happens, step by step:
The receptors switch on. The medicine activates PPAR-gamma receptors inside cells. [1]
Cells respond better to insulin. Activated cells become more sensitive to insulin. [1]
More sugar leaves the blood. Cells get better at taking sugar out of your bloodstream. [1]
The liver makes less sugar. This adds to the drop in blood sugar. [1]
This is why TZDs are called insulin sensitizers. They target insulin resistance, one of the core problems in type 2 diabetes. [1]
What are the types of thiazolidinediones?
The two types of thiazolidinediones are pioglitazone (brand name Actos) and rosiglitazone (brand name Avandia). [1]
Both work in the same way. Your healthcare provider chooses the medicine and dose for you. [1]
What are the usual doses of thiazolidinediones?
The usual dose of pioglitazone is 15 to 30 mg once daily, and the usual dose of rosiglitazone is 4 mg once daily. [1]
Medicine | Brand name | Usual dose | Maximum daily dose |
Pioglitazone | Actos | 15–30 mg once daily | 45 mg |
Rosiglitazone | Avandia | 4 mg once daily | 8 mg |
Source: [1]
Always take thiazolidinediones exactly as prescribed. Never change your dose on your own. [1]
How do you know if your thiazolidinedione dose is working?
Your thiazolidinedione dose may not be working if your blood sugar readings stay high or you still have diabetes symptoms. [1]
Tell your provider if you notice:
These can be signs of high blood sugar (hyperglycemia).
What should you do if you miss a dose of a thiazolidinedione?
If you miss a dose of a thiazolidinedione, take it as soon as you remember, unless your next dose is only a few hours away. [1]
For example, if you usually take it with breakfast and remember at lunch, it is fine to take it then. [1]
Never take two doses at once to make up for a missed one. [1]
What are the side effects and risks of thiazolidinediones?
The most common side effects of thiazolidinediones are swelling in the legs and ankles and weight gain. [1]
Thiazolidinediones can also raise the risk of more serious problems. Both medicines carry an FDA boxed warning: they can cause or worsen heart failure and must not be used by people with serious (class III or IV) heart failure. Call your provider right away for fast weight gain, swelling or shortness of breath. [1]
Type | What to watch for | Notes |
Common side effect | Swelling in legs and ankles | Also called edema |
Common side effect | Weight gain | — |
Increased risk | Broken bones | See osteoporosis |
Increased risk | — | |
Increased risk | Liver damage | — |
Increased risk | Bladder cancer | Pioglitazone only |
Increased risk | Especially when combined with other diabetes medicines |
Source: [1]
What are the benefits of thiazolidinediones?
The main benefit of thiazolidinediones is controlling blood sugar levels in type 2 diabetes. [1]
Other benefits include:
Better insulin response. They help your body respond better to insulin. [1]
Cholesterol and fatty liver. There is evidence that pioglitazone can improve cholesterol levels and help improve fatty liver. [1][9]
Easy to combine. You can take TZDs with metformin and sulfonylureas; pioglitazone can also be used with insulin, but rosiglitazone with insulin is not recommended. [1]
Read more about how these medicines fit together in our diabetes medications guide, our metformin (biguanides) guide and our guide to pioglitazone and metformin extended-release tablets.
Who should not take thiazolidinediones?
People who are pregnant or planning a pregnancy should not take thiazolidinediones. [1]
Adults over 18 with type 2 diabetes can take them, but they may not be suitable if you have: [1]
Condition | Why it matters |
Liver disease | TZDs can raise the risk of liver damage |
Kidney disease | Listed as a reason the medicine may not be suitable |
Bladder cancer or blood in your pee | Pioglitazone is linked to bladder cancer risk |
Heart failure | TZDs can raise the risk of heart failure |
Source: [1]
Before starting, tell your provider your full medical history and every medicine and supplement you take. [1]
How do thiazolidinediones fit into diabetes care?
Thiazolidinediones are one of several medicines a provider may recommend to keep blood sugar in a healthy range. [1]
Medicine is only one part of the plan. Eating nutritious foods and staying active are also part of treating type 2 diabetes. [1]
Conclusion
Thiazolidinediones are once-daily tablets that tackle insulin resistance directly. They help fat, muscle and liver cells respond better to insulin, and they help the liver release less sugar. [1]
Pioglitazone and rosiglitazone work the same way. They can be paired with metformin or sulfonylureas, and pioglitazone (not rosiglitazone) with insulin. [1]
The trade-offs are real: swelling, weight gain, and higher risks of heart failure, fractures, liver damage and, with pioglitazone, bladder cancer. They are not for use in pregnancy. [1]
If you have type 2 diabetes, ask your healthcare provider whether a TZD suits your health history, and contact them with any questions about your diabetes medicine. [1]
Keep learning: Explore our complete diabetes guide, compare options in our SGLT2 inhibitors guide, and check our prediabetes guide if blood sugar runs in your family. Share this article with someone who has just been prescribed pioglitazone or rosiglitazone.
FAQ
What are thiazolidinediones used for?
Thiazolidinediones are used to treat type 2 diabetes by helping the body use insulin more efficiently. They are also used off-label for polycystic ovary syndrome (PMOS) and may help with cirrhosis in people with MASLD. [1]
How do thiazolidinediones lower blood sugar?
Thiazolidinediones lower blood sugar by activating PPAR-gamma receptors in fat, muscle and liver cells. This makes the cells respond better to insulin and take more sugar from the blood, while the liver makes less sugar. [1]
What is the difference between pioglitazone and rosiglitazone?
Pioglitazone and rosiglitazone are the two thiazolidinediones, and they work in the same way. Pioglitazone is usually taken at 15–30 mg once daily (maximum 45 mg), rosiglitazone at 4 mg once daily (maximum 8 mg), and only pioglitazone is linked to bladder cancer risk. [1]
What are the most common side effects of thiazolidinediones?
The most common side effects of thiazolidinediones are swelling in the legs and ankles and weight gain. They can also raise the risk of broken bones, heart failure, liver damage and low blood sugar when combined with other diabetes medicines. [1]
Can thiazolidinediones be taken with metformin or insulin?
Thiazolidinediones can be taken with metformin and sulfonylureas; pioglitazone can also be used with insulin, but rosiglitazone with insulin is not recommended. Combining them with other diabetes medicines can raise the risk of low blood sugar, so your provider will monitor you. [1]
Who should not take thiazolidinediones?
People who are pregnant or planning a pregnancy should not take thiazolidinediones. They may also not be suitable for people with liver disease, kidney disease, heart failure, bladder cancer or blood in the urine. [1]
What should I do if I miss a dose of pioglitazone or rosiglitazone?
If you miss a dose of pioglitazone or rosiglitazone, take it as soon as you remember unless your next dose is only a few hours away. Never take two doses at once. [1]
When should I call my doctor while taking a thiazolidinedione?
Call your doctor while taking a thiazolidinedione if your blood sugar stays high or you feel very thirsty, tired or pee often. Also contact them about any new swelling, weight gain or questions about your medicine. [1]
How long does it take for a thiazolidinedione to work?
Thiazolidinediones work slowly, and it can take several weeks to a few months to see their full effect on blood sugar. Your provider will check your A1C to see how well the medicine is working.
Do thiazolidinediones cause low blood sugar?
On their own, they rarely cause low blood sugar. The risk goes up when they are taken with insulin or a sulfonylurea, so learn the signs of low blood sugar, such as shakiness, sweating and confusion.
Related Reading
Biguanides (Metformin): Uses, How They Work, Side Effects and Risks explains metformin, the usual first medicine for type 2 diabetes.
Pioglitazone and Metformin Extended-Release Tablets: Managing Type 2 Diabetes covers the combination tablet that pairs pioglitazone with metformin.
Understanding SGLT2 Inhibitors: A Patient Guide to Type 2 Diabetes Management describes another class of diabetes pills and their heart and kidney benefits.
DPP-4 Inhibitors (Gliptins): How They Work, Examples, Side Effects, and Who Should Avoid Them explains how gliptins lower blood sugar and their common side effects.
References
Cleveland Clinic. Thiazolidinediones (TZDs): What They Are & Side Effects. Cleveland Clinic. Last updated January 14, 2026. https://my.clevelandclinic.org/health/treatments/thiazolidinediones
Eggleton JS, Jialal I. Thiazolidinediones. StatPearls. Last updated February 20, 2023. https://www.ncbi.nlm.nih.gov/books/NBK551656/
Lincoff AM, Wolski K, Nicholls SJ, et al. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA. 2007;298(10):1180-1188. PMID 17848652. https://doi.org/10.1001/jama.298.10.1180
Loke YK, Singh S, Furberg CD. Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. CMAJ. 2009;180(1):32-39. PMID 19073651. https://doi.org/10.1503/cmaj.080486
Kernan WN, Viscoli CM, Furie KL, et al. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. N Engl J Med. 2016;374(14):1321-1331. PMID 26886418. https://doi.org/10.1056/NEJMoa1506930
Arnold SV, Inzucchi SE, Echouffo-Tcheugui JB, et al. Understanding Contemporary Use of Thiazolidinediones. Circ Heart Fail. 2019;12(6):e005855. PMID 31129998. https://doi.org/10.1161/CIRCHEARTFAILURE.118.005855
Lebovitz HE. Thiazolidinediones: the Forgotten Diabetes Medications. Curr Diab Rep. 2019;19(12):151. PMID 31776781. https://doi.org/10.1007/s11892-019-1270-y
Rizos CV, Kei A, Elisaf MS. The current role of thiazolidinediones in diabetes management. Arch Toxicol. 2016;90(8):1861-1881. PMID 27165418. https://doi.org/10.1007/s00204-016-1737-4
Sayadishahraki M, Mirfendereski S, Kachuei A, et al. Effect of Pioglitazone on Nonalcoholic Fatty Liver Disease in Morbid Obese Patients; a Randomized Controlled Trial. Adv Biomed Res. 2023;12:27. PMID 37057246. https://doi.org/10.4103/abr.abr_354_21
Diabetes UK. Thiazolidinediones (glitazones). Diabetes UK. Last updated June 18, 2024. https://www.diabetes.org.uk/about-diabetes/looking-after-diabetes/treatments/tablets-and-medication/thiazolidinediones-glitazones
Further reading: MedlinePlus. Pioglitazone. MedlinePlus Drug Information. Last updated October 15, 2026. https://medlineplus.gov/druginfo/meds/a699016.html
Medical disclaimer
This article is for general educational purposes and does not replace professional medical advice, diagnosis or treatment. Do not start, stop or change any medicine without talking to your healthcare provider. If you have chest pain, severe shortness of breath, sudden swelling or signs of very low blood sugar, seek emergency care right away.
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