Exercise and GLP-1 RA on Insulin Secretion

Study Overview
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Brief Summary
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The purpose of this study is to determine the effect of endurance exercise on insulin secretory capacity, alone or in addition to treatment with the glucagon-like-peptide receptor agonist semaglutide, in patients with type 2 diabetes.

Detailed Description
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The effects of endurance exercise alone or in addition to treatment with glucagon-like- peptide receptor agonists on insulin secretory capacity, will be determined in patients with type 2 diabetes. Included patients will be randomized to either 12 weeks of endurance exercise training 3 times a week or therapeutical treatment with semaglutide for 3 months followed by 12 weeks of endurance exercise training 3 times a week. Insulin secretory capacity will be determined by hyperglycemic clamp method before and after.

Official Title
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Effects of 12 Weeks of Endurance Exercise Training Alone or in Combination With Glucagon Like Peptide 1 Receptor Agonist (GLP-1 RA) Treatment on Insulin Secretory Capacity in Type 2 Diabetes

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Behavioral: Endurance exercise training
* Drug: Semaglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with type 2 diabetes BMI 28-35 Moderately preserved insulin secretory capacity (determined by glucagon test) Exclusion Criteria: Insulin treatment Hypertension grade 3 Heart disease Medical history with pancreatitis Diagnosed with neuropathy Excessive alcohol consumption Any condition that would interfere with the protocol.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semaglutide treatment<br>3 months of therapeutic semaglutide treatment | Drug: Semaglutide<br>* 3 months of therapeutic treatment with semaglutide<br>|
| Experimental: Semaglutide and Endurance exercise<br>12 weeks of endurance exercise concomitant to semaglutide treatment | Behavioral: Endurance exercise training<br>* Ergometer cycling at 70 % of VO2 max, 45 minutes, 3 times a week<br>Drug: Semaglutide<br>* 3 months of therapeutic treatment with semaglutide<br>|
| Experimental: Endurance exercise<br>12 weeks of endurance exercise | Behavioral: Endurance exercise training<br>* Ergometer cycling at 70 % of VO2 max, 45 minutes, 3 times a week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin secretion | By hyperglycemic clamp | Change from baseline insulin secretion after Exercise intervention(12 weeks). | 
| Insulin secretion | By hyperglycemic clamp | Change from baseline insulin secretion after 3 months of therapeutic semaglutide treatment | 
| Insulin secretion | By hyperglycemic clamp | Change from baseline insulin secretion after 3 months of combined exercise and therapeutic semaglutide treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin secretion | By Oral glucose tolerance test | Before and after (3 days) Exercise intervention (12 weeks). Before and after 3 months of therapeutic semaglutide treatment | 
| insulin sensitivity | Derived from hyperglycemic clamp and HOMA-IR | Before and after (2 days) Exercise intervention(12 weeks). Before and after 3 months of therapeutic semaglutide treatment | 
| Changes in plasma bone markers | Changes in baseline CTX, PNIP, Osteocalcin and alkaline phosphatase | Before and after (2 days) Exercise intervention (12 weeks). Before and after 3 months of therapeutic semaglutide treatment | 
| Glucose homeostasis | Changes in HbA1c | Before and after (2 days) Exercise intervention (12 weeks). Before and after 3 months of therapeutic semaglutide treatment | 
| Cardiorespiratory fitness | Changes in maximal oxygen uptake | Before and after (3 days) Exercise intervention (12 weeks). Before and after 3 months of therapeutic semaglutide treatment | 
| Body composition | By DXA | Before and after (3 days) Exercise intervention (12 weeks). Before and after 3 months of therapeutic semaglutide treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin secretion, Beta cell function