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

• ClinicalTrials.gov Identifier: NCT04854083
• Recruitment Status: Not yet recruiting
• First Posted: April 22, 2021
• Last Update Posted: April 22, 2021
• Sponsor: Kirsi Pietiläinen
• Collaborators: University of Helsinki; Turku University Hospital
• Information provided by (Responsible Party): Kirsi Pietiläinen, Helsinki University Central Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Type2 Diabetes	Drug: Semaglutide, 1.34 mg/mL; Drug: Placebo	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Estimated Study Start Date: May 2021
• Estimated Primary Completion Date: August 2024
• Estimated Study Completion Date: August 2024

Arms and Interventions

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 Name: 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.

Outcome Measures

Primary Outcome Measures :

1. HbA1c [ Time Frame: from baseline to 12 months ]
   Change in HbA1c (%)

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Kirsi H Pietiläinen, MD PhD; +358505992295; kirsi.pietilainen@helsinki.fi

Sponsors and Collaborators

Kirsi Pietiläinen

University of Helsinki

Turku University Hospital

Investigators

• Principal Investigator: Kirsi Pietiläinen, MD PhD; Helsinki University Central Hospital

More Information

• Responsible Party: Kirsi Pietiläinen, Professor, Helsinki University Central Hospital
• ClinicalTrials.gov Identifier: NCT04854083
• Other Study ID Numbers: 2020
• First Posted: April 22, 2021
• Last Update Posted: April 22, 2021
• Last Verified: April 2021

• 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

Keywords provided by Kirsi Pietiläinen, Helsinki University Central Hospital:

weight loss; dieting

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases