Semaglutide as an Adjunct to Dieting in the Treatment of Type 2 Diabetes (MitoSema)

Semaglutide as an Adjunct to Dieting in the Treatment of Type 2 Diabetes - Effects on Glucose Metabolism, Prevention of Weight Regain and Peripheral Tissue Metabolic Activation

The pharmacological approaches in the treatment of type 2 diabetes (T2DM) have advanced radically during the last decades. However, focus on long-term management of body weight, which is an essential part of treatment success, is often lacking. Excluding surgery, there are only a few effective treatment methods for obesity. Management of obesity is also greatly challenged by weight regain, which is common after a successful lifestyle intervention. Weight regain typically results in the deterioration of glucose homeostasis in T2DM. However, understanding the pathomechanisms of weight regain and subsequent worsening of glucose homeostasis is still insufficient. Therefore, T2DM treatment programs that target long-term weight management have been scarce. This study aims to fill the gaps in the current knowledge by advancing the development of treatment programs for T2DM that simultaneously head for improved glucose metabolism and improved long-term body weight control.

Study Overview

• Status: Recruiting
• Conditions: Type2 Diabetes
• Intervention / Treatment: Drug: Semaglutide, 1.34 mg/mL; Drug: Placebo

Detailed Description

In this randomized, double-blind, parallel, placebo-controlled trial we compare the effects of semaglutide 1.34 mg/ml vs. normal dieting by randomizing the patients with both T2DM and overweight/obesity (BMI ≥27) (n=50, aged ≥18 to < 65 years) to two groups: both groups participate in a similar lifestyle treatment to induce weight loss, but one group gets an add-on of semaglutide 1.34mg/ml while the other is treated with placebo. Additionally, a reference group of healthy normal weight non-diabetic individuals (BMI ≤ 25 kg/m2, n=25, aged ≥18 to < 65 years) are included as controls at the initiation of the study.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Kirsi H Pietiläinen, MD PhD; Phone Number: +358505992295; Email: kirsi.pietilainen@helsinki.fi

Study Locations

• Finland
  • Helsinki, Finland
    • Recruiting
    • University of Helsinki

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 years and <65 years
• BMI: ≥27 kg/m2
• T2DM (HbA1c ≥ 6.0% if on anti-diabetic medication or HbA1c≥6.5% if non- medicated)
• Participant is willing and able to give informed consent for participation in the study

Exclusion Criteria:

• Contraindication to trial drugs
• Use of insulin or GLP-1RAs (during the past 3 months)
• Use of anti-obesity drugs (during the past 3 months)
• Weight change of >5% during the past 3 months
• Bariatric surgery or planned bariatric surgery during the trial
• History of pancreatitis
• Impaired renal function (GFR<30 ml/min/1.73m2)
• Impaired hepatic function (ALAT>2 x upper limit normal)
• Clinically significant active cardiovascular disease
• Clinically significant abnormality in the ECG
• Cancer (except basal or squamous cell skin cancers)
• Major psychiatric disease (such as severe depression, bipolar disorder, schizophrenia)
• Substance abuse
• Learning disability
• Females of childbearing potential not using adequate contraceptive methods
• Pregnancy
• Lactation
• Any other condition that in the opinion of the investigator could interfere with the conduction of the study or interpretation of the study results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Semaglutide; The intervention study for the patients with T2DM begins with a low-calorie diet (LCD) phase run-in for 13 weeks. During re-introduction of food, the participants will be assigned to semaglutide 1.34mg/ml treatment for 44 weeks (dose escalation in total 8 weeks, maintenance period for 36 weeks).	Drug: Semaglutide, 1.34 mg/mL; The low-calorie diet (LCD) has a phase run-in period for 13 weeks for all participants including 8 weeks of total LCD followed 5-week gradual re-introduction of food (replacement of the VLCD products by one meal/week). During re-introduction of food, the subjects will be randomly assigned to semaglutide 1.34mg/ml (subcutaneous administration, dose escalation 0.25 mg once weekly for 4 weeks, 0.5 mg once weekly for 4 weeks, where after 1.0 mg once weekly) until the end of the study (12 months). The participants will receive lifestyle counselling throughout the study.; Other Names: Ozempic
PLACEBO_COMPARATOR: Placebo; The intervention study for the patients with T2DM begins with a low-calorie diet (LCD) phase run-in for 13 weeks. During re-introduction of food, the participants will be assigned to placebo treatment for 44 weeks (dose escalation in total 8 weeks, maintenance period for 36 weeks).	Drug: Placebo; The low-calorie diet (LCD) has a phase run-in period for 13 weeks for all participants including 8 weeks of total LCD followed 5-week gradual re-introduction of food (replacement of the VLCD products by one meal/week). During re-introduction of food, the subjects will be randomly assigned to placebo (subcutaneous administration, dose escalation 0.25 mg once weekly for 4 weeks, 0.5 mg once weekly for 4 weeks, where after 1.0 mg once weekly) until the end of the study (12 months). The participants will receive lifestyle counselling throughout the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c	Change in HbA1c (%)	from baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c	Change in HbA1c (%)	from baseline to 6 months
Fasting plasma glucose	Change in fasting plasma glucose (mmol/l)	from baseline to 6 and 12 months
Body weight	Change in body weight (kg)	from baseline to 6 and 12 months
Percentage of patients reaching ≥5%,10% & 15% weight loss		from baseline to 6 and 12 months
Waist circumference	Change in waist circumference (cm)	from baseline to 6 and 12 months
Change in appetite and eating habits, control of eating	Using questionnaire Control of Eating (CoEQ)	from baseline to 6 and 12 months
Change in appetite and eating habits, binge eating	Using questionnaires Binge Eating Scale(BES), Questionnaire on Eating and Weight Patterns (QEWP)	from baseline to 6 and 12 months
Change in appetite and eating habits, emotional, external and restraint eating	Using questionnaire Dutch Eating Behaviour Questionnaire (DEBQ)	from baseline to 6 and 12 months
Blood pressure	Change in blood pressure (mmHg)	from baseline to 6 and 12 months
Plasma lipids	Change in lipids (total cholesterol, LDL, HDL, TAG) (mmol/l)	from baseline to 6 and 12 months
Changes in concomitant antidiabetic medications	Change in number of antidiabetic medications	from baseline to 6 and 12 months
Changes in concomitant antihypertensive medications	Change in number of antihypertensive medications	from baseline to 6 and 12 months
Changes in concomitant lipid medications	Change in number of lipid medications	from baseline to 6 and 12 months
Mitochondrial DNA quantification	Change in mitochondrial DNA (mtDNA) copy number, RNA expression of mtDNA encoded genes in adipose tissue and skeletal muscle	from baseline to 6 and 12 months
Change in the transcriptomics profile of adipose tissue and skeletal muscle	Change in the transcriptomics profile by qPCR and/or RNA sequencing	from baseline to 6 and 12 months
Change in the oxygen uptake and perfusion in subcutaneous and intra-abdominal adipose tissue, brown adipose tissue, skeletal muscle, gut and liver	Change in the oxygen uptake and perfusion measured by PET/CT (in vivo)	from baseline to 12 months

Collaborators and Investigators

• Sponsor: Kirsi Pietiläinen
• Collaborators: Turku University Hospital; University of Helsinki
• Investigators: Principal Investigator: Kirsi Pietiläinen, MD PhD, Helsinki University Central Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 17, 2022
• Primary Completion (ANTICIPATED): August 1, 2025
• Study Completion (ANTICIPATED): August 1, 2025

Study Registration Dates

• First Submitted: April 9, 2021
• First Submitted That Met QC Criteria: April 20, 2021
• First Posted (ACTUAL): April 22, 2021

Study Record Updates

• Last Update Posted (ACTUAL): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 17, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: weight loss; dieting
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 2020

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