Efficacy of Semaglutide in Glycemic Control, Weight Loss, and Improving Lipidogram- Role of Baseline Vitamin D Levels (Semaglutide)

July 4, 2025 updated by: Hillel Yaffe Medical Center

Efficacy of Semaglutide in Glycemic Control, Weight Loss, and Improving Lipid Profile- the Role of Baseline Vitamin D Levels

Objective: Semaglutide, a glucagon-like peptide-1 receptor agonist, is an established therapy for type 2 diabetes (T2D), offering robust glycemic control and weight reduction. Vitamin D has been implicated in metabolic regulation, yet its influence on semaglutide-induced outcomes remains unclear.

Research Design and Methods: the investigators conducted a cross-sectional analysis of 5,300 adults with T2D, enrolled in Leumit Health Services, who initiated semaglutide therapy between February 1, 2019, and December 31, 2022. All patients had documented serum 25-hydroxyvitamin D [25(OH)D] levels prior to treatment initiation. Metabolic outcomes- including glycemic control (HbA1c), body mass index (BMI), and lipid profile- were assessed at 12 months. Associations between baseline 25(OH)D levels and metabolic changes were evaluated using multivariable regression models, adjusted for demographic and clinical covariates.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, was initially approved for the treatment of type 2 diabetes mellitus (T2DM) due to its superior glucose-lowering efficacy compared to oral antidiabetic agents, with a favorable safety profile regarding hypoglycemia risk. In June 2021, the U.S. Food and Drug Administration (FDA) approved higher doses of semaglutide for long-term weight management, marking the first pharmacologic advancement in obesity treatment since 2014 (FDA, 2021).

Semaglutide exerts its effects through multiple mechanisms, including delayed gastric emptying, appetite suppression, enhanced glucose-stimulated insulin secretion from pancreatic β-cells, and reduced glucagon secretion. In individuals with overweight and obese, semaglutide induces substantial and sustained weight reduction, with an average decrease of approximately 14.9% of baseline body weight.

The pathophysiology of T2DM varies across racial and ethnic groups. For example, T2DM in Caucasian populations is primarily characterized by obesity and insulin resistance, whereas in East Asians, including the Japanese, early-onset β-cell dysfunction and insulin deficiency predominate. Consequently, the glycemic response to semaglutide is not uniform across populations. Notably, semaglutide predominantly enhances first-phase insulin secretion, an effect that may be particularly beneficial in individuals with insulin deficiency. Several blinded, controlled trials have demonstrated superior glycemic control with semaglutide in Asian populations, reinforcing the significance of insulin resistance versus insulin deficiency in determining its net metabolic effects.

While genetic and ethnic determinants of semaglutide response are largely non-modifiable, certain adjunctive interventions may optimize its therapeutic effects. Among these, vitamin D has emerged as a potential modulator of molecular pathways involved in metabolic regulation. In regard to diabetes control, vitamin D is a key immunomodulatory factor, and preclinical studies have demonstrated its protective effects against β-cell dysfunction in diabetes. In murine models, early vitamin D administration mitigated the inflammatory insults responsible for β-cell destruction, thereby preventing autoimmune diabetes onset. These findings are supported by human studies in prediabetic and newly diagnosed T2DM individuals, in whom long-term vitamin D supplementation (six months) significantly improved peripheral insulin sensitivity and β-cell function, potentially delaying diabetes progression.

Obesity has long been linked to vitamin D deficiency. While the role of vitamin D in weight loss remains debated, a recent meta-analysis highlighted its potential clinical efficacy in optimizing weight reduction. Specifically, three months of vitamin D supplementation in obese women significantly augmented weight loss and improved metabolic parameters.

Given the high prevalence of vitamin D deficiency, particularly among individuals with obesity and T2DM, supplementation may offer metabolic benefits.

To date, the relationship between vitamin D status and the metabolic effects of semaglutide has not been well characterized. In this retrospective cross-sectional study, The investigators aimed to investigate the association between baseline vitamin D levels and semaglutide-induced glycemic control and weight loss in an Israeli T2DM population.

Study Type

Observational

Enrollment (Actual)

5300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Hadera, Israel, 333300
        • Leumit Health ccare system

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

diabetic patients on semaglutide treatment and with available baseline vitamin D levels

Description

Inclusion Criteria:

  • Diabetes type II treated with semaglutide
  • Available baseline vitamin D levels

Exclusion Criteria:

  • Missing serum 25-hydroxyvitamin D (25[OH]D) data
  • Pregnant or lactating females

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
diabetic patients on semaglutide
we tested the relation between baseline vitamin D levels and metabolic amplification of semaglutide metabolic effects
Drug: semaglutide
testing the effect of baseline vitamin D on metabolic effects of semaglutide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
relative weight loss measured by BMI
Time Frame: 12 months from semaglutide initiation
testing semaglutide induced weight loss as a function of baseline vitamin D levels
12 months from semaglutide initiation
glycemic control using Hgb1C
Time Frame: 12 months from semaglutide initiation
testing semaglutide induced glycemic control as a function of baseline vitamin D levels
12 months from semaglutide initiation
lipid control using LDL and TG
Time Frame: 12 months from semaglutide initiation
testing semaglutide induced lipid control as a function of baseline vitamin D levels
12 months from semaglutide initiation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hillel Yaffe Medical Center

Investigators

  • Principal Investigator: rami abo fanne, MD PhD, Hillel Yaffe Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 18, 2023

Primary Completion (Actual)

December 21, 2024

Study Completion (Actual)

April 30, 2025

Study Registration Dates

First Submitted

April 29, 2025

First Submitted That Met QC Criteria

June 27, 2025

First Posted (Actual)

June 29, 2025

Study Record Updates

Last Update Posted (Actual)

July 9, 2025

Last Update Submitted That Met QC Criteria

July 4, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0034-23-LEU
  • Non applicable (Other Grant/Funding Number: Leumit health care system)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

data is personal and secured

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe