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

Kirsi Pietiläinen50 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Interventions

Semaglutide, 1.34 mg/mLDRUG

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.

PlaceboDRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

HbA1c

Change in HbA1c (%)

Time frame: from baseline to 12 months

Secondary Outcomes

HbA1c

Change in HbA1c (%)

Time frame: from baseline to 6 months

Fasting plasma glucose

Change in fasting plasma glucose (mmol/l)