None listed
Conditions
Brief summary
The study will determine the effects of 12 weeks treatment with the 'long-acting' glucagon-like peptide-1 (GLP-1) agonist, semaglutide once weekly (QW), on the rate of stomach emptying, glycaemia, blood pressure (BP) and heart rate (HR) following a standardised mashed potato meal, in type 2 diabetes (T2DM). The study will also assess the effect of cessation of semaglutide on gastric emptying at 1 and 4 weeks post-cessation. This is a randomised parallel designed study. Subjects recruited into the study who pass screening criteria will be randomised to receive semaglutide QW or matching placebo. They will have a gastric emptying study performed using the gold standard technique (scintigraphy) at baseline, at 12 weeks, and 1 and 4 weeks post cessation of semaglutide QW. Immediately following the first gastric emptying study they will commence treatment with semaglutide QW or Placebo, administered subcutaneously at weekly intervals. Glucose absorption, blood pressure, blood glucose and plasma insulin will be assessed during each of the gastric emptying measurements.
Interventions
Semaglutide 0.25-1mg or matching placebo once weekly sc for 12 weeks. Semaglutide will be uptitrated from 0.25mg for 4 weeks, followed by 0.5mg for 4 weeks and then 1mg for 4 weeks. The injection is administered by one of the investigators to remove any issues relating to compliance and adherence to the intervention.
A gastric emptying study using the gold standard technique (scintigraphy) will be performed by a qualified nuclear medicine technologist, at baseline (ie before treatment), at 12 w
Semaglutide 0.25-1mg or matching placebo once weekly sc for 12 weeks. Semaglutide will be uptitrated from 0.25mg for 4 weeks, followed by 0.5mg for 4 weeks and then 1mg for 4 weeks. The injection is administered by one of the investigators to remove any issues relating to compliance and adherence to the intervention. A gastric emptying study using the gold standard technique (scintigraphy) will be performed by a qualified nuclear medicine technologist, at baseline (ie before treatment), at 12 weeks after commencing semaglutide, and 1 week and 4 weeks post cessation of semaglutide. Following an overnight fast (14h solids, 12h liquids), participants will consume a carbohydrate mashed potato meal (369 kcal) comprising 65 g powdered potato and 20 g glucose reconstituted with 250 ml boiling water and labelled with 20 MBq 99mTc-calcium phytate to measure gastric emptying using scintigraphy. The meal will include 3g 3-O-methylglucose (3-OMG, Sigma Aldrich, USA) and 1000mg of paracetamol. Fasting requirements will be confirmed prior to administration of the test meal. Paracetamol 1000mg will not be added to the test meal during gastric emptying studies at 1 and 4 weeks post drug cessation.
Sponsors
University of Adelaide
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
• Male or female participants aged 40 – 80 years • Female subjects who are post-menopausal; or pre-menopausal with surgical contraception (such as tubal ligation) or an intrauterine device. Pre-menopausal women will require a confirmed negative urine ß-hCG pregnancy test at screening visit. • T2DM (World Health Organisation (WHO) criteria) managed by diet alone or on metformin • Glycated haemoglobin (HbA1c) greater than or equal to 6.0% and less than or equal to 8.5%, in the last 4 months prior to enrolment in the study • Body mass index (BMI) 25 – 40 kg/m2 • Haemoglobin and ferritin in the normal range for gender and age. • Participant has provided written informed consent.
Exclusion criteria
• Evidence of renal disease (i.e. a creatinine clearance cut-off of < 50 ml/min. Calculated creatinine clearance will be determined as follows using the Cockcroft-Gault equation: Cr clearance = [140 - age (years) x weight (kg)] / [0.814 x serum creatinine (µmol/L)] (For female subjects, multiply Cr clearance x 0.85)(24) • Iron stores, or liver function tests outside the following ranges: Alanine aminotransferase (ALT) < 55 U/L Alkaline phosphatase (ALP) 30 - 110 U/L Aspartate transaminase (AST) < 45 U/L Total bilirubin 6 - 24 µmol/L Haemoglobin 115 – 155 g/L (Females) 135 – 172 g/L (Males) Ferritin 15 – 200 µg/L (Females) 30 – 300 µg/L (Males) • Hepatic or cardiovascular disease, pancreatitis (subjects with past history of acute or chronic pancreatitis, gastric surgery, or known gastroparesis on history or screening biochemistry tests. • Participants with any history of cancer, except for basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy = 12 months prior to screening or other malignancies treated with apparent success with curative therapy = 5 years prior to screening will be excluded. • History of any clinically significant disease or disorder which may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer’s ability to participate in the study. • Personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). • History of hyperthyroidism or uncontrolled hypothyroidism. • Chronic gastrointestinal symptoms as assessed by questionnaire. • Use of drugs potentially affecting gastrointestinal motility (corticosteroids; anti-emetics (dopamine antagonists, 5HT-3 receptor antagonists), laxatives, prokinetic agents, anticholinergic agents, cholinergic agents, opioid medications, erythromycin). • Current use of anticoagulants. • Inability to abstain from smoking for 12 hours prior to the gastric emptying tests. • Consumption of greater than 2 units alcohol daily on a regular basis. • Known or suspected history of alcohol or drug abuse, as judged by the Investigator. • History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, or history of hypersensitivity to semaglutide or drugs with a similar chemical structure or its components. • Known hypersensitivity to IV infusion equipment, plastics, adhesive or silicone, or know history of hypotension or infusion site reactions with IV administration of other medicines • Participation in any research studies involving exposure to ionising radiation exceeding 2.5mSv in the previous 12 months • Donated blood in the past 3 months • Vegetarian
Outcome results
None listed