Semaglutide and Intestinal Iron Absorption

The Effect of Parenterally Administred Semaglutide on Intestinal Iron Absorption in Individuals With Type 2 Diabetes Mellitus

Semaglutide belongs to a group of long-acting glucagon-like peptide 1 receptor agonists (GLP-1). Disorders in iron absorption have been linked to numerous medication, dietary, and nutrient interactions thus far. The study aimed to determine whether there is an effect of concomitant parenteral administration of semaglutide and oral iron preparations on iron absorption in patients with type 2 diabetes (T2DM).

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus Type 2; Iron Absorption
• Intervention / Treatment: Drug: semaglutide

Detailed Description

Type 2 diabetes mellitus (T2DM) affects over 537 million people worldwide, making it a major chronic and progressive health problem among adults. Novel approaches to managing T2DM have been developed as a result of medical advancements. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are appealing options for the treatment of T2DM, since they efficiently reduce body weight and haemoglobin A1C with a minimal risk of hypoglycaemia.

Semaglutide, a long-acting GLP-1 RA, has a very high structural homology with endogenous GLP-1, high binding affinity to albumin, and resistance to degradation by the intestinal enzyme dipeptidyl peptidase-4. Because of these characteristics and his extended half-life, it can be used once weekly. Similar to all other GLP-1 RAs, semaglutide decreases gastrointestinal motility and slows stomach emptying. Delay in stomach emptying and intestinal motility can interfere with vitamin, mineral, and drug absorption. Iron is one of the essential micronutrients in the human body. On average, 10 - 20 mg of iron is consumed daily through food, but only 1 - 2 mg of iron is absorbed in the duodenum and the first section of the small intestine. It has been shown that drugs which decrease gastrointestinal motility can interfere with iron absorption. However, the relationship between parenteral semaglutide administration and intestine iron absorption has not been the subject of any prior studies. Thus, this study aimed to determine whether there is an effect of parenteral administration of semaglutide on iron absorption in patients with T2DM.

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Croatia
  • Zagreb, Croatia, 10000
    • University Hospital Dubrava

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• T2DM patients
• ages between 45 and 65
• with poorly managed T2DM (HbA1c ≥ 7%)
• who are candidates for treatment intensification and beginning of parenterally administered semaglutide

Exclusion Criteria:

• hypersensitivity to GLP-1 RAs,
• adequately controlled with current glucose-lowering medications,
• already treated with GLP-1 RA,
• type 1 diabetes mellitus or any other form of diabetes,
• hemochromatosis,
• iron deficiency anaemia,
• sideropaenia,
• severe chronic illnesses,
• malignant neoplasms of any site,
• chronic infectious diseases,
• chronic rheumatic inflammatory diseases,
• malabsorption syndrome,
• inflammatory bowel disease,
• history of gastrointestinal tract reduction surgery,
• medications that interfere with absorption,
• perimenopausal women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: T2DM subjects before and at week 10 of semaglutide therapy; Patient demographic and clinical data was collected and entered into a database made specifically for the study. The patients were examined, and their vital signs and body measures were recorded. Before the introduction of semaglutide therapy all participants completed an oral absorption iron test (OIAT). As described in previous studies, OIAT was conducted in an outpatient setting. Following the initial OIAT therapy with semaglutide was started. Each subject received parenterally administered one-weekly semaglutide. To enhance glycaemic control, the therapy was up-titrated every four weeks. Initially, the dose was set at 0.25 mg once a week, four weeks later, it was raised to 0.5 mg once weekly, and four weeks after that, it was increased to 1 mg once weekly. After reaching the maximum maintenance dosage of 1 mg for two weeks, each T2DM patient completed a follow-up OIAT at week 10 of the study. Data from the first and subsequent OIATs were analysed statistically.

Drug: semaglutide; Patient demographic and clinical data was collected and entered into a database made specifically for the study. The patients were examined, and their vital signs and body measures were recorded. Before the introduction of semaglutide therapy all participants completed an oral absorption iron test (OIAT). As described in previous studies, OIAT was conducted in an outpatient setting. Following the initial OIAT therapy with semaglutide was started. Each subject received parenterally administered one-weekly semaglutide. To enhance glycaemic control, the therapy was up-titrated every four weeks. Initially, the dose was set at 0.25 mg once a week, four weeks later, it was raised to 0.5 mg once weekly, and four weeks after that, it was increased to 1 mg once weekly. After reaching the maximum maintenance dosage of 1 mg for two weeks, each T2DM patient completed a follow-up OIAT at week 10 of the study. Data from the first and subsequent OIATs were analysed statistically.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
General objective	Number of T2DM participant that will have reduction in intestinal iron absorption after the semaglutide administration	10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Specific objectives	Correlation between serum ferritin levels prior to the OIAT and the degree of iron absorption during semaglutide administration in patients with T2DM.	10 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sex differences	Sex-dependent difference in intestinal iron absorption with the administration of semaglutide in patients with T2DM.	10 weeks

Collaborators and Investigators

• Sponsor: University Hospital Dubrava
• Investigators: Principal Investigator: Srećko Marušić, MD, PhD, UH Dubrava

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Actual): April 1, 2024
• Study Completion (Actual): April 1, 2024

Study Registration Dates

• First Submitted: October 2, 2024
• First Submitted That Met QC Criteria: October 3, 2024
• First Posted (Actual): October 8, 2024

Study Record Updates

• Last Update Posted (Estimated): December 5, 2024
• Last Update Submitted That Met QC Criteria: December 2, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: semaglutide; type 2 diabetes mellitus; iron; oral iron absorption test
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Diabetes Mellitus; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; Semaglutide
• Other Study ID Numbers: sema-iron

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: I have to learn about what IPD would be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No