Can levothyroxine treatment reduce urinary albumin excretion rate in patients with early type 2 diabetic nephropathy and subclinical hypothyroidism? A randomized double-blind and placebo-controlled study
Abstract
OBJECTIVE: To investigate the effect of levothyroxine (LT4) therapy on urinary albumin excretion rate (UAER) in early type 2 diabetic nephropathy (DN) and subclinical hypothyroidism (SCH) patients with mildly increased thyroid stimulating hormone (TSH) levels and serum thyroid peroxidase antibody (TPO-Ab) positivity. METHODS: Application of randomized double-blind and placebo-controlled methods. A total of 136 normotensive patients with early type 2 DN and SCH (TSH 4.0-7.0 mIU/L and TPO-Ab positive) were selected, and were randomly divided into two groups for LT4 or placebo treatments, respectively. Changes in UAER, serum creatinine, glomerular filtration rate (GFR), blood pressure, serum uric acid and lipids in patients before and after 48 weeks of treatment were examined and compared between groups. RESULTS: There were no statistically significant differences in the baseline characteristics of study participants between two treatment groups (p > 0.05 for all). After 48 weeks of treatment, compared to the placebo treatment, the LT4 treatment was more effective in reducing total cholesterol (p < 0.05). Further comparison of therapy-related differences between groups showed that the LT4 treatment was better in reducing UAER, low-density lipoprotein cholesterol and uric acid than the placebo group (p < 0.01 for all). CONCLUSION: The LT4 treatment may decrease UAER and exert kidney protection effects in early type 2 DN and SCH patients with mildly increased TSH levels and serum TPO-Ab positivity. However, due to the short duration of follow-up and small number of cases, the results of this study need future trials with larger numbers of patients and longer follow-up periods to verify whether such a strategy can provide durable benefits.
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In the Peng Liu et al. 2015 randomized controlled trial, insomnia occurred in 2 of 60 patients receiving levothyroxine versus 0 of 59 patients receiving placebo, with a risk ratio of 4.92 (95% CI 0.23-104.66), which was not statistically significant.
“Insomnia was reported in 2 of 60 patients (3.33%) vs. 0 of 59 patients (0%) with (RR 4.92, 95% CI 0.23–104.66)”
From Risk of cardiac, neuropsychiatric and musculoskeletal adverse events with levothyroxine: Systematic review (2026) · cites this paper as [18]
In a randomised, placebo-controlled study, LT4 treatment reduced serum uric acid and excretion of albumin in patients with diabetic nephropathy and subclinical hypothyroidism, consistent with a renoprotective effect.
“In another randomised, placebocontrolled study, LT4 treatment reduced serum uric acid and excretion of albumin in a trial in patients with diabetic nephropathy and subclinical hypothyroidism, an effect consistent with a renoprotective effect”
From Pharmacodynamic and Therapeutic Actions of Levothyroxine (2021) · cites this paper as [41]
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- Authors
- Liu, P., Liu, R., Chen, X., Chen, Y., Wang, D., Zhang, F., & Wang, Y.
- Affiliations
- Affiliated Hospital of Qingdao University (CN)
- Taishan Medical University (CN)
- Taian City Central Hospital (CN)
- Corresponding author
- Zhang, Fengmei
- Wang, Yangang
- Venue
- Current Medical Research and Opinion
- Publisher
- Informa Healthcare
- Published
- 2015-10-23
- Volume
- 31
- Issue
- 12
- Pages
- 2233-2240
- ISSN
- 0300-7995 (ISSN-L)
- 1473-4877
- OpenAlex
- W2177779490
- Cited by
- 36
- References
- 35
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 7 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 2 · 2016: 1
- FWCI
- 1.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Medical Research and Opinion (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Keywords
- levothyroxine, type 2 diabetic nephropathy, subclinical hypothyroidism, urinary albumin excretion rate, thyroid-stimulating hormone, thyroid peroxidase antibodies, renal protection, cholesterol, uric acid, glomerular filtration rate, serum creatinine
- MeSH terms
- Adult, Albumins, Autoantibodies, Cholesterol, Diabetic Nephropathies, Double-Blind Method, Female, Glomerular Filtration Rate, Humans, Hypothyroidism, Kidney, Kidney Function Tests, Cholesterol, LDL, Male, Middle Aged, Thyroxine, Uric Acid
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