# Combined Treatment of Type 2 Diabetes and Hypothyroidism: Impact of Oral Semaglutide and Levothyroxine on Cardiometabolic and Thyroid Parameters: A 6-Month Comparative Study

**Authors:** Dana-Mihaela Tilici, Ruxandra-Mihaela Costinescu, Diana Loreta Paun, Daniela Stegaru, Beatrice Mihaela Grecu, Mirona Costea, Cristian Guja

PMC · DOI: 10.3390/epidemiologia7020041 · 2026-03-04

## TL;DR

This study shows that combining semaglutide and levothyroxine improves heart and metabolic health in patients with both type 2 diabetes and hypothyroidism.

## Contribution

The study demonstrates additive cardiometabolic benefits of combining semaglutide and levothyroxine in patients with T2DM and hypothyroidism.

## Key findings

- Combined therapy reduced LDL cholesterol by 12.7% and increased HDL by 9.0% in patients with T2DM and hypothyroidism.
- Glycemic control improved with a 7.7% reduction in HbA1c in the combined treatment group.
- BMI decreased by 4.9% in the combined treatment group over six months.

## Abstract

Background/Objectives: Type 2 diabetes (T2DM) and hypothyroidism often coexist, worsening cardiometabolic risk. Oral semaglutide and levothyroxine each improve metabolic parameters, but the effect of combined therapy is understudied. This study aimed to evaluate whether oral semaglutide administered concomitant with levothyroxine provides additive benefits on lipid profile, glycemic control, and body weight in patients with both conditions. Methods: This prospective comparative observational study assessed a total of 210 patients who were enrolled (70 per group) with a 6-month follow-up. Group A (T2DM and hypothyroidism) received semaglutide and levothyroxine, group B (hypothyroidism only) received levothyroxine, and group C (T2DM only) received oral semaglutide. Lipid profile, glycemic profile (HbA1c), thyroid profile, and anthropometric parameters were comparable across groups at baseline and after 6 months. Results: Group A demonstrated significant improvements in lipid parameters: LDL-cholesterol decreased by 12.7%, HDL increased by 9.0%, and triglycerides decreased by 6.7% (all comparisons p < 0.001 unless otherwise specified). In contrast, group B experienced worsening lipid profiles (LDL increased by 11.0%, HDL decreased by 0.5%, and triglycerides increased by 9.1%), while group C showed modest changes (LDL increased by 4.5%). Glycemic control improved among diabetic patients, with HbA1c declining by 7.7% in group A and 12.6% in group C. Body mass index (BMI) decreased in groups A (4.9%) and C (6.0%). Conclusions: The concurrent administration of oral semaglutide and levothyroxine produces additive cardiometabolic advantages in individuals with T2DM and hypothyroidism. These findings suggest that combined treatment may optimize metabolic outcomes in this particularly high-risk population.

## Linked entities

- **Chemicals:** semaglutide (PubChem CID 56843331), levothyroxine (PubChem CID 5819), HDL (PubChem CID 6323542)
- **Diseases:** Type 2 diabetes (MONDO:0005148), hypothyroidism (MONDO:0005420)

## Full-text entities

- **Genes:** LDLR (low density lipoprotein receptor) [NCBI Gene 3949] {aka LDLCQ2}, LPL (lipoprotein lipase) [NCBI Gene 4023] {aka HDLCQ11, LIPD}, GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, CALCA (calcitonin related polypeptide alpha) [NCBI Gene 796] {aka CALC1, CGRP, CGRP-I, CGRP-alpha, CGRP1, CT}
- **Diseases:** gastric stasis (MESH:D018589), autoimmune thyroiditis (MESH:D013967), thyroid cancer (MESH:D013964), TD (MESH:D013959), Metabolic Diseases (MESH:D008659), goiter (MESH:D006042), autoimmune (MESH:D001327), MTC (MESH:C536911), Weight loss (MESH:D015431), tumor (MESH:D009369), hypertension (MESH:D006973), thyroid (MESH:D013966), CMT (MESH:C537989), hypothalamic or pituitary deficiency (MESH:D007029), peripheral arterial disease (MESH:D058729), atrophic (MESH:D020966), injury to (MESH:D014947), thyroid nodules (MESH:D016606), diabetic complications (MESH:D048909), nephropathy (MESH:D007674), Hypothyroidism (MESH:D007037), T2DM (MESH:D003924), obese (MESH:D009765), Diabetes (MESH:D003920), retinopathy (MESH:D058437), neuropathy (MESH:D009422), autoimmune hypothyroidism (MESH:C562768), hyperthyroidism (MESH:D006980)
- **Chemicals:** blood sugar (MESH:D001786), glucose (MESH:D005947), DeltaTSH (-), cholesterol (MESH:D002784), Levothyroxine (MESH:D013974), RA (MESH:D011883), Exenatide (MESH:D000077270), triglyceride (MESH:D014280), Lipid (MESH:D008055)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC13010780/full.md

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Source: https://tomesphere.com/paper/PMC13010780