From the Guidelines
Thiazide diuretics should be used with caution in diabetic patients due to their potential to worsen glycemic control and increase the risk of new-onset diabetes. According to the guidelines for antihypertensive treatment updated after the ALLHAT study 1, thiazide diuretics may not be the best choice for patients with diabetes, as they can raise blood glucose levels and increase the risk of new-onset diabetes. The study found that blood glucose and new-onset diabetes rose in the chlorthalidone group, suggesting that thiazide-like diuretics alone or combined with a β-blocker should be avoided in patients at risk of developing diabetes 1.
Some key points to consider when using thiazide diuretics in diabetic patients include:
- Decreased insulin sensitivity and impaired insulin secretion
- Increased risk of new-onset diabetes by approximately 20-30% with long-term use
- Potential to worsen lipid profiles by increasing total cholesterol, LDL, and triglycerides
- Mechanism involves potassium depletion, which impairs pancreatic beta-cell function and insulin release
When treating hypertensive diabetic patients, alternative first-line agents like ACE inhibitors or ARBs are generally preferred. If thiazides must be used in diabetic patients, lower doses are recommended, and regular monitoring of blood glucose, electrolytes, and lipid levels is essential. Combining thiazides with potassium-sparing diuretics or potassium supplements may help mitigate some metabolic effects. Overall, the use of thiazide diuretics in diabetic patients requires careful consideration of the potential risks and benefits, and alternative treatments should be considered whenever possible.
From the FDA Drug Label
WARNINGS ... Diabetes and Hypoglycemia: Latent diabetes mellitus may become manifest and diabetic patients given thiazides may require adjustment of their insulin dose. Thiazide diuretics are not strictly contraindicated in diabetes, but they may exacerbate the condition.
- Key issue: Thiazides can cause latent diabetes mellitus to become manifest.
- Clinical consideration: Diabetic patients given thiazides may require adjustment of their insulin dose 2.
From the Research
Thiazide Diuretics and Diabetes
Thiazide diuretics are contraindicated in diabetes due to their potential to worsen glucose control and increase the risk of new-onset diabetes. The key points to consider are:
- Thiazide diuretics can increase fasting plasma glucose levels, with a mean difference of 0.27 mmol/L (4.86 mg/dL) compared to non-thiazide agents or placebo 3.
- The risk of impaired glucose tolerance or incident diabetes is higher in patients receiving thiazide diuretics, although the change in blood glucose level varies across different trials 3.
- Thiazide-induced hypokalemia is associated with increased blood glucose, and treatment of hypokalemia may reverse glucose intolerance and possibly prevent the future development of diabetes 4.
- The use of thiazide diuretics in patients with diabetes may lead to diabetes progression, although the benefits of thiazide diuretics in terms of cardiovascular event reduction may outweigh the risks 5, 6.
Mechanisms and Risks
The mechanisms responsible for the increased incidence of diabetes with thiazide diuretics are not fully elucidated, but may involve:
- Thiazide-induced hypokalemia, which can increase blood glucose levels 4.
- The effects of thiazide diuretics on glucose metabolism, including increased glucose production and decreased insulin sensitivity.
- The potential for thiazide diuretics to worsen glucose control in patients with existing diabetes, particularly at higher doses 3.
Clinical Considerations
When using thiazide diuretics in patients with diabetes, clinicians should:
- Closely monitor glucose control and adjust treatment as needed 6.
- Consider the potential benefits and risks of thiazide diuretics in terms of cardiovascular event reduction and diabetes progression 5, 6.
- Be aware of the potential for thiazide-induced hypokalemia and take steps to prevent or treat it 4.