From the Guidelines
Thiazide diuretics worsen glycemic control through several mechanisms that affect insulin sensitivity and pancreatic function, and alternative antihypertensives like ACE inhibitors or angiotensin receptor blockers might be preferable for high-risk patients. These medications, such as hydrochlorothiazide, chlorthalidone, and indapamide, can decrease insulin secretion from pancreatic beta cells and reduce peripheral tissue sensitivity to insulin 1. Hypokalemia, a common side effect of thiazides, plays a significant role in this process by impairing insulin release from the pancreas. Additionally, thiazides can cause magnesium depletion, which further compromises insulin action. The medications may also activate the renin-angiotensin-aldosterone system and increase sympathetic nervous system activity, both of which can contribute to insulin resistance.
Some key points to consider:
- Thiazide diuretics can increase the risk of developing diabetes, especially in patients with pre-existing risk factors such as obesity, family history of diabetes, or metabolic syndrome 1.
- The use of thiazide diuretics in combination with other medications, such as beta-blockers, may increase the risk of developing diabetes 1.
- Alternative antihypertensives, such as ACE inhibitors or angiotensin receptor blockers, may be preferable for patients with diabetes or at risk of developing diabetes, as they have been shown to have beneficial effects on insulin sensitivity and glucose metabolism 1.
- Regular monitoring of blood glucose levels is important for patients on thiazide therapy, especially during the first few months of treatment when the risk of developing hyperglycemia is highest.
It is essential to weigh the benefits and risks of thiazide diuretics in each patient and consider alternative treatment options when necessary to minimize the risk of worsening glycemic control.
From the FDA Drug Label
Diabetes and Hypoglycemia: Latent diabetes mellitus may become manifest and diabetic patients given thiazides may require adjustment of their insulin dose. Thiazide diuretics, such as hydrochlorothiazide, can worsen glycemic control because they may cause latent diabetes mellitus to become manifest and can affect the management of diabetic patients, potentially requiring an adjustment of their insulin dose 2.
From the Research
Mechanisms of Thiazide Diuretics on Glycemic Control
- Thiazide diuretics are known to worsen glycemic control in patients, particularly those with hypertension 3, 4, 5, 6, 7.
- The exact mechanisms are not fully understood, but studies suggest that thiazide diuretics can cause impaired glucose tolerance, biochemical diabetes, and insulin resistance 4.
- The effect of thiazide diuretics on glucose tolerance is dose-related, with higher doses leading to greater impairment 4, 5.
- Thiazide-induced hypokalemia (low potassium levels) is also associated with increased blood glucose levels, suggesting a potential link between potassium levels and glucose metabolism 7.
Clinical Implications
- Thiazide diuretics can increase fasting plasma glucose (FPG) levels compared to non-thiazide agents or placebo 5.
- Patients receiving lower doses of thiazides (≤25 mg daily) may experience less change in FPG levels compared to those receiving higher doses 5.
- The use of thiazide diuretics in patients with prediabetes or type 2 diabetes has been challenged due to associated metabolic adverse events, including new-onset diabetes 6.
- However, the benefits of thiazide diuretics in reducing cardiovascular events and mortality may outweigh the risks of worsening glucose control in patients with type 2 diabetes and hypertension 6.
Treatment Considerations
- Treatment with a lower dose of thiazide diuretics may reduce or avoid glycemic changes 5.
- Combining thiazide diuretics with potassium-sparing agents may help mitigate the risk of hypokalemia and associated glucose intolerance 4, 7.
- Alternative antihypertensive agents, such as calcium channel blockers or alpha-blockers, may have fewer adverse effects on glucose metabolism 4.