From the Guidelines
Allopurinol can be used in patients with hyperglycemia, as the two conditions are not directly contraindicated, and its use should be guided by the patient's kidney function and uric acid levels, as recommended by the 2017 EULAR guidelines 1.
Key Considerations
- Allopurinol is primarily prescribed to treat gout and other conditions involving high uric acid levels by inhibiting xanthine oxidase, the enzyme responsible for uric acid production.
- The standard dosing begins at 100 mg daily and may be titrated up to 300-800 mg daily depending on uric acid levels and kidney function.
- When treating a patient who has both hyperglycemia and conditions requiring allopurinol, it's essential to monitor both conditions separately as they require distinct management approaches.
- Hyperglycemia should be addressed through appropriate diabetes medications, dietary changes, and lifestyle modifications, taking into account the patient's kidney function, as recommended by the 2007 KDOQI guidelines 1.
- There is some evidence suggesting that allopurinol may actually have modest beneficial effects on insulin resistance in some patients, though this is not a primary reason to prescribe it.
- Kidney function should be monitored regularly in these patients, as both diabetes and allopurinol can affect renal function, and dosage adjustments may be necessary in patients with impaired kidney function, as noted in the 2020 American College of Rheumatology guideline for the management of gout 1.
Monitoring and Dosage Adjustments
- Patients with decreased kidney function (CKD stages 3 to 5) have increased risks for hypoglycemia and require careful monitoring and dosage adjustments of their diabetes medications, as well as their allopurinol dose.
- The 2007 KDOQI guidelines provide recommendations for dosing of drugs used to treat hyperglycemia in patients with CKD stages 3 to 5, which should be taken into account when managing patients with both hyperglycemia and gout.
- The 2017 EULAR guidelines recommend starting allopurinol at a low dose (100 mg/day) and increasing by 100 mg increments every 2–4 weeks if required, to reach the uricaemic target, and adjusting the dose based on kidney function.
From the Research
Allopurinol and Hyperglycemia
- Allopurinol has been shown to have a positive effect on glycemic control in patients with type 2 diabetes mellitus, with studies indicating that it can improve glycated haemoglobin (HbA1c) levels and reduce glycemic variability 2.
- A cross-sectional study found that patients with type 2 diabetes who were taking allopurinol had lower HbA1c levels and improved glycemic variability compared to those who were not taking the medication 2.
- Another study found that long-term allopurinol therapy can improve renal function in patients with type 2 diabetes and asymptomatic hyperuricemia, which may also have a positive effect on hyperglycemia 3.
- A meta-analysis of randomized controlled trials found that allopurinol can reduce serum uric acid levels and improve renal function in patients with diabetes, which may also have a positive effect on hyperglycemia 4.
- A randomized, single-blind, placebo-controlled trial found that high-dose and long-term allopurinol therapy can improve endothelial function in diabetic normotensive patients, which may also have a positive effect on hyperglycemia 5.
Mechanism of Action
- Allopurinol works by inhibiting xanthine oxidase, an enzyme that contributes to the production of uric acid, which is associated with hyperglycemia and other cardiovascular risk factors 6.
- By reducing uric acid levels, allopurinol may also reduce oxidative stress and improve endothelial function, which can have a positive effect on hyperglycemia 5.
Clinical Implications
- The use of allopurinol in patients with hyperglycemia may be beneficial in improving glycemic control and reducing the risk of cardiovascular complications 2, 3, 4, 5.
- However, more research is needed to fully understand the effects of allopurinol on hyperglycemia and to determine the optimal dosage and treatment duration 4.