Alpha-melanocyte stimulatory hormone (α-MSH) is a melanocyte-stimulating hormone produced by the hypothalamus and released from the pituitary gland. It acts as an agonist to the melanocortin 5 receptor (MC5R) in human skeletal muscle, playing a role in glucose uptake and disposal. This study aims to investigate whether α-MSH can enhance glucose tolerance in patients with Type 2 Diabetes Mellitus (T2DM).

Pre-clinical studies in mice have shown improved glucose clearance with α-MSH infusion, particularly in skeletal muscle. Research has demonstrated that α-MSH improves glucose tolerance in healthy humans by promoting glucose uptake in skeletal muscle cells.

Therefore this study seeks to answer the question of whether alpha-MSH improves glucose tolerance in patients with T2DM. This will be addressed through measuring the impact of α-MSH infusion in patients with T2DM. The research involves a double-blinded, randomized, placebo-controlled crossover study.

Inclusion Criteria:

• People with T2DM treated with oral or injectable medications which have been stable for 3 months, but not insulin therapy for type 2 diabetes.
• Stable body weight and HbA1c for at least 3 months
• The participant is capable of giving written informed consent
• The participant is able to read, comprehend and record information written in English

Exclusion Criteria:

• Previous or current psychiatric diagnosis listed in DSM-V Axis 1.
• Significant current or past medical or psychiatric history that, in the opinion of the investigators, contraindicates their participation.
• History of type 1 diabetes mellitus.
• History of endocrine disorder.
• History of ischaemic heart disease, hypertension (current BP > 160/95 mmHg), heart failure, cardiac arrhythmia, peripheral vascular or cerebrovascular disease.
• History or presence of significant respiratory, gastrointestinal, hepatic, oncological, neurological or renal disease or other condition that in the opinion of the Investigators may affect participant safety or outcome measures.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• History of sensitivity to any of the peptides, or components thereof, or a history of drug or other allergy that, in the opinion of the investigators, contraindicates their participation.
• Use of current regular prescription or over-the-counter medications that in the opinion of the Investigators may affect participant safety or outcome measures.
• Clinically significant abnormalities in screening electrocardiogram (ECG) or blood tests abnormalities which in the opinion of the study physician, is clinically significant and represents a safety risk.
• Current pregnancy or breast-feeding in female participants (the investigators would advise using contraception for the duration of the study).
• Pulse rate <40 or >100 beats per minute OR systolic blood pressure >160 and <100 and a diastolic blood pressure >95 and <50 in the semi-supine position.
• The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the first experimental visit in the current study: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Exposure to more than 3 new investigational medicinal products within 12 months prior to the screening.
• Participants who have donated, or intend to donate, blood within three months before the screening visit or following study visit completion.