Systematic Review to Gauge the Effect of Levothyroxine Substitution on Progression of Diabetic Nephropathy in Patients With Hypothyroidism and Type 2 Diabetes Mellitus

Diabetes mellitus (DM) and thyroid dysfunction are two disorders that are closely related. This systematic review aimed to investigate the effect of levothyroxine supplementation on diabetic nephropathy in type 2 diabetic patients with co-existing thyroid dysfunction. We explored medical databases such as PubMed, Medline, Multidisciplinary Digital Publishing Institute (MDPI), and Cochrane Library for relevant medical literature. The papers were screened, and 12 research papers involving 10,371 patients were identified after applying eligibility criteria and quality assessment using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The included papers analyzed the effect of aberrant thyroid profile on kidney disease in diabetic individuals and the role that achieving euthyroid status with levothyroxine supplementation could play in diabetic nephropathy. Reduced free triiodothyronine (FT3) was the most common independent factor associated with diabetic microvascular and macrovascular complications. Levothyroxine (LT4) regimen was more effective than the placebo in lowering urinary albumin excretion rate (UAER), low-density lipoprotein cholesterol, and uric acid and decreasing oxidative stress overall. However, replacement therapy's effect may differ in the short and long terms. Thyroid hormone replacement therapy (THRT) may reduce the risk of diabetic nephropathy and cardiovascular disease (CVD) development in hypothyroid patients, but more randomized trials are needed to confirm the effect of THRT.