Clinical trial NCT04854083: Semaglutide as an Adjunct to Dieting in the Treatment of Type 2 Diabetes
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Type2 Diabetes
Keywords: weight loss
dieting
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
Collaborators: name: University of Helsinki
name: Turku University Hospital
First posted: 2021-04-22
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: HbA1c
timeFrame: from baseline to 12 months
Secondary outcomes:
measure: HbA1c
timeFrame: from baseline to 6 months
measure: Fasting plasma glucose
timeFrame: from baseline to 6 and 12 months
measure: Body weight
timeFrame: from baseline to 6 and 12 months
measure: Percentage of patients reaching ≥5%,10% & 15% weight loss
timeFrame: from baseline to 6 and 12 months
measure: Waist circumference
timeFrame: from baseline to 6 and 12 months
measure: Change in appetite and eating habits, control of eating
timeFrame: from baseline to 6 and 12 months
measure: Change in appetite and eating habits, binge eating
timeFrame: from baseline to 6 and 12 months
measure: Change in appetite and eating habits, emotional, external and restraint eating
timeFrame: from baseline to 6 and 12 months
measure: Blood pressure
timeFrame: from baseline to 6 and 12 months
measure: Plasma lipids
timeFrame: from baseline to 6 and 12 months
measure: Changes in concomitant antidiabetic medications
timeFrame: from baseline to 6 and 12 months
measure: Changes in concomitant antihypertensive medications
timeFrame: from baseline to 6 and 12 months
measure: Changes in concomitant lipid medications
timeFrame: from baseline to 6 and 12 months
measure: Mitochondrial DNA quantification
timeFrame: from baseline to 6 and 12 months
measure: Change in the transcriptomics profile of adipose tissue and skeletal muscle
timeFrame: from baseline to 6 and 12 months
measure: Change in the oxygen uptake and perfusion in subcutaneous and intra-abdominal adipose tissue, brown adipose tissue, skeletal muscle, gut and liver
timeFrame: from baseline to 12 months
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: University of Helsinki
Study officials:
affiliation: Helsinki University Central Hospital
name: Kirsi Pietiläinen, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: