Type2 Diabetes
Conditions
Keywords
weight loss, dieting
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.
Interventions
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.
DRUGPlacebo
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.
Sponsors
University of Helsinki
Turku University Hospital
Kirsi Pietiläinen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HbA1c | from baseline to 12 months | Change in HbA1c (%) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fasting plasma glucose | from baseline to 6 and 12 months | Change in fasting plasma glucose (mmol/l) |
| Body weight | from baseline to 6 and 12 months | Change in body weight (kg) |
| Percentage of patients reaching ≥5%,10% & 15% weight loss | from baseline to 6 and 12 months | — |
| Waist circumference | from baseline to 6 and 12 months | Change in waist circumference (cm) |
| Change in appetite and eating habits, control of eating | from baseline to 6 and 12 months | Using questionnaire Control of Eating (CoEQ) |
| Change in appetite and eating habits, binge eating | from baseline to 6 and 12 months | Using questionnaires Binge Eating Scale(BES), Questionnaire on Eating and Weight Patterns (QEWP) |
| Change in appetite and eating habits, emotional, external and restraint eating | from baseline to 6 and 12 months | Using questionnaire Dutch Eating Behaviour Questionnaire (DEBQ) |
| HbA1c | from baseline to 6 months | Change in HbA1c (%) |
| Plasma lipids | from baseline to 6 and 12 months | Change in lipids (total cholesterol, LDL, HDL, TAG) (mmol/l) |
| Changes in concomitant antidiabetic medications | from baseline to 6 and 12 months | Change in number of antidiabetic medications |
| Changes in concomitant antihypertensive medications | from baseline to 6 and 12 months | Change in number of antihypertensive medications |
| Changes in concomitant lipid medications | from baseline to 6 and 12 months | Change in number of lipid medications |
| Mitochondrial DNA quantification | 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 |
| Change in the transcriptomics profile of adipose tissue and skeletal muscle | from baseline to 6 and 12 months | Change in the transcriptomics profile by qPCR and/or RNA sequencing |
| Change in the oxygen uptake and perfusion in subcutaneous and intra-abdominal adipose tissue, brown adipose tissue, skeletal muscle, gut and liver | from baseline to 12 months | Change in the oxygen uptake and perfusion measured by PET/CT (in vivo) |
| Blood pressure | from baseline to 6 and 12 months | Change in blood pressure (mmHg) |
Countries
Finland
Contacts
Primary ContactKirsi H Pietiläinen, MD PhD
Outcome results
None listed