Does hydrochlorothiazide cause weight gain
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Does Hydrochlorothiazide Cause Weight Gain?
Hydrochlorothiazide (HCTZ) is a commonly prescribed thiazide diuretic used to manage hypertension and fluid retention. Given its widespread use, understanding its potential side effects, including weight gain, is crucial for both patients and healthcare providers.
Hydrochlorothiazide and Weight Gain: Clinical Evidence
Insulin Resistance and Fat Accumulation
Research indicates that hydrochlorothiazide can lead to adverse metabolic effects, including insulin resistance and fat accumulation. A study comparing hydrochlorothiazide with candesartan and placebo found that hydrochlorothiazide treatment resulted in increased liver fat content and a reduction in the subcutaneous to visceral abdominal adipose tissue ratio. These changes were associated with aggravated insulin resistance and low-grade inflammation, which are factors that can contribute to weight gain and metabolic syndrome1.
Weight Changes in Pregnancy
In a study involving pregnant women, the prophylactic use of hydrochlorothiazide was associated with a lower incidence of excessive weight gain compared to a placebo. Specifically, 7.7% of the hydrochlorothiazide group experienced excessive weight gain versus 13.9% in the placebo group. This suggests that hydrochlorothiazide may not necessarily cause weight gain and might even help in managing weight during pregnancy2.
Metabolic Side Effects
Another study comparing hydrochlorothiazide with captopril in hypertensive patients found that hydrochlorothiazide negatively impacted glucose and lipid metabolism. The drug increased basal insulin concentration and late insulin response to glucose, which could potentially lead to weight gain over time due to decreased insulin sensitivity. Additionally, hydrochlorothiazide significantly increased serum cholesterol and triglyceride levels, further contributing to an unfavorable metabolic profile3.
Acute Decompensated Heart Failure
In patients with acute decompensated heart failure, adding hydrochlorothiazide to usual treatment with furosemide showed a trend towards greater daily weight reduction. This suggests that in the context of heart failure, hydrochlorothiazide may aid in weight loss rather than weight gain, likely due to its diuretic effects4.
Conclusion
The evidence on hydrochlorothiazide and weight gain is mixed and context-dependent. While hydrochlorothiazide can lead to metabolic changes that might contribute to weight gain, such as increased insulin resistance and lipid levels, it does not universally cause weight gain. In some cases, such as in pregnant women or patients with heart failure, it may even help manage or reduce weight. Therefore, the impact of hydrochlorothiazide on weight should be considered within the broader context of individual patient health and treatment goals.
Sources and full results
Most relevant research papers on this topic
Hydrochlorothiazide, but not Candesartan, Aggravates Insulin Resistance and Causes Visceral and Hepatic Fat Accumulation: The Mechanisms for the Diabetes Preventing Effect of Candesartan (MEDICA) Study
Hydrochlorothiazide treatment worsens insulin resistance and causes visceral and liver fat accumulation, while candesartan treatment reduces blood pressure similarly.
RCT
Highly CitedProphylactic use of hydrochlorothiazide in pregnancy.
Long-term, prophylactic use of hydrochlorothiazide in pregnancy did not alter the incidence of preeclampsia, hypertension, prematurity, congenital anomalies, or perinatal mortality.
RCT
Large Human TrialA comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension.
Hydrochlorothiazide has adverse effects on glucose and lipid metabolism, while captopril shows beneficial or no effects, potentially reducing the risk for diabetes and coronary heart disease.
RCTHighly CitedEffect of adding hydrochlorothiazide to usual treatment of patients with acute decompensated heart failure: a randomized clinical trial
Adding hydrochlorothiazide 50 mg to furosemide significantly increased weight loss in patients with acute decompensated heart failure and congestion.
RCT
Rigorous JournalEffect of adding hydrochlorothiazide to usual treatment of patients with acute decompensated heart failure: a randomized clinical trial
Adding hydrochlorothiazide to furosemide in acute decompensated heart failure patients led to a significant synergistic effect on weight loss, but not significant difference in daily body weight reduction compared to placebo.
RCTRigorous JournalThe evaluation of the developmental toxicity of hydrochlorothiazide in mice and rats.
Hydrochlorothiazide has no significant effect on maternal or developmental toxicity in mice, and its maternal NOAEL is 300 mg/kg/day, based on decreased maternal weight gain at 1000 mg/kg/day.
Non-RCT
Animal StudyEffect of adding hydrochlorothiazide to usual treatment of patients with acute decompensated heart failure: a randomized clinical trial
Adding hydrochlorothiazide 50 mg to furosemide resulted in a synergistic effect on weight loss in patients with acute decompensated heart failure and congestion.
RCTPlasma renin activity in pregnant women with oedema treated with hydrochlorothiazide.
Hydrochlorothiazide treatment in pregnant women with oedema shows different reactivity in the renin-angiotensin system, suggesting two different types of pathophysiology in pregnancy-associated edema.
Non-RCTThe antidiuretic effect of chronic hydrochlorothiazide treatment in rats with diabetes insipidus: water and electrolyte balance.
Chronic hydrochlorothiazide treatment in diabetes insipidus rats leads to a reduction in extracellular volume without causing a significant overall sodium deficit.
Non-RCTAnimal StudyCombination of high-dose furosemide and hydrochlorothiazide in the treatment of refractory congestive heart failure.
Adding hydrochlorothiazide to high-dose furosemide is a powerful diuretic tool for patients with severe congestive heart failure and impaired renal function, but should be used carefully due to potential side effects (hypokalaemia).
Non-RCTHighly Cited