From the Guidelines
Thiazide diuretics worsen glycemic control primarily through several mechanisms that affect insulin sensitivity and pancreatic beta cell function, and their use should be carefully considered in patients at high risk for developing diabetes, as suggested by the 2016 American Diabetes Association standards of medical care in diabetes 1.
Mechanisms of Thiazide-Induced Hyperglycemia
- Thiazide diuretics reduce potassium levels in the body (hypokalemia), which impairs insulin secretion from pancreatic beta cells and decreases glucose uptake by tissues.
- They also cause magnesium depletion, which further contributes to insulin resistance.
- Additionally, thiazides like hydrochlorothiazide and chlorthalidone directly decrease peripheral glucose utilization and may increase hepatic glucose production.
- The sympathetic nervous system activation caused by volume depletion can also contribute to insulin resistance.
Patient Risk Factors
- Patients with pre-existing diabetes, metabolic syndrome, or family history of diabetes are at higher risk for thiazide-induced hyperglycemia.
- The risk of new-onset diabetes is also increased with the use of thiazide diuretics, particularly when used at high doses, as reported in the ALLHAT study 1.
Recommendations for Clinical Practice
- When prescribing thiazides, it's advisable to use the lowest effective dose, monitor blood glucose levels regularly, and consider alternative antihypertensives like ACE inhibitors or ARBs in patients at high risk for developing diabetes, as recommended by the 2013 ESH/ESC guidelines for the management of arterial hypertension 1.
- The association with a potassium-sparing agent should be considered when using diuretics, as there is evidence that hypokalaemia worsens glucose intolerance, as noted in the European guidelines on cardiovascular disease prevention in clinical practice 1.
From the FDA Drug Label
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 in diabetic patients, potentially causing latent diabetes mellitus to become manifest. As a result, diabetic patients taking thiazides may need to adjust their insulin dose to maintain adequate blood sugar control 2.
From the Research
Mechanisms of Thiazide Diuretics on Glycemic Control
- Thiazide diuretics are known to worsen glycemic control in patients with hypertension, as evidenced by increased fasting glucose levels 3, 4, 5.
- The exact mechanisms are not fully understood, but it is thought that thiazide diuretics may impair glucose tolerance and increase insulin resistance 4.
- The effects of thiazide diuretics on glucose metabolism are dose-related, with higher doses associated with greater impairments in glucose tolerance 4, 5.
Clinical Implications
- Thiazide diuretics are associated with an increased risk of new-onset diabetes and worsening glycemic control in patients with prediabetes or type 2 diabetes 6.
- However, the benefits of thiazide diuretics in reducing cardiovascular events and mortality may outweigh the risks of worsening glycemic control 6.
- Clinicians should closely monitor glycemic control in patients taking thiazide diuretics, especially when used concurrently with other medications that may affect glucose levels, such as statins 7.
Factors Influencing Glycemic Effects
- The type and dose of thiazide diuretic used may influence the degree of glycemic impairment, with lower doses associated with less severe effects 5.
- Combination therapy with other antihypertensive agents, such as beta blockers, may also exacerbate glycemic effects 3.
- Patient characteristics, such as baseline glucose levels and presence of diabetes, may also impact the glycemic effects of thiazide diuretics 3, 4.