Digital Dietary Intervention for Patients Receiving GLP-1 Receptor Agonist Therapy

Inclusion criteria

• Age 21-65 years inclusive at the time of signing informed consent.
• Male or female.
• Overweight with at least one comorbidity, including diabetes mellitus; arterial hypertension of at least 130/85 mmHg or use of antihypertensive medication; dyslipidemia defined as triglycerides of at least 1.7 mmol/L, reduced HDL cholesterol below 1.0 mmol/L in men or below 1.3 mmol/L in women, or use of lipid-lowering medication; cardiovascular disease; respiratory or joint disease; non-alcoholic fatty liver disease; sleep disorders; or other comorbidities.
• For participants with overweight: body mass index of 25.0-29.9 kg/m² for the Caucasian population or 23.0-27.4 kg/m² for the Asian population, together with abdominal obesity defined as waist circumference of at least 94 cm in men and 80 cm in women of the European population, or at least 90 cm in men and 80 cm in women of the Asian population.
• Class I-III obesity where diet combined with physical activity has been ineffective, defined as weight loss of less than 5% over 3 months.
• Class I obesity: body mass index of 30.0-34.9 kg/m² for the Caucasian population or 27.5-32.4 kg/m² for the Asian population.
• Class II obesity: body mass index of 35.0-39.9 kg/m² for the Caucasian population or 32.5-37.4 kg/m² for the Asian population.
• Type 2 diabetes mellitus with HbA1c of at least 6.5% (48 mmol/mol), fasting glucose of at least 6.1 mmol/L in capillary whole blood or at least 7.0 mmol/L in venous plasma, glucose of at least 11.1 mmol/L two hours after an oral glucose tolerance test, or random glucose of at least 11.1 mmol/L.
• Body mass index of at least 25 kg/m² and no more than 40 kg/m² at screening.
• Already receiving, or prescribed, GLP-1 receptor agonist therapy with semaglutide by the treating physician independently of the study. The study does not prescribe or modify this therapy.
• Stable doses of medications for chronic conditions, including antihypertensive agents and statins, for at least 8 weeks before screening.
• Ownership of an iOS or Android smartphone with internet access and willingness to download and use the "NutriSteppe" application if assigned to the intervention group.
• Ability and willingness to provide written informed consent and comply with study procedures.
• Women of childbearing potential must use effective contraception throughout the study.

Exclusion criteria

• Diagnosis of type 1 diabetes mellitus.
• History of diabetic ketoacidosis or hyperglycemic hyperosmolar state.
• Initiation of GLP-1 receptor agonist therapy less than 4 weeks before screening.
• Current insulin therapy.
• Personal or family history of medullary thyroid carcinoma.
• Personal history of multiple endocrine neoplasia type 2 (MEN2).
• History of acute or chronic pancreatitis.
• Active gallbladder disease or history of gallbladder disease within 6 months before screening.
• Severe gastrointestinal disease, including gastroparesis.
• Major cardiovascular event within 6 months before screening, including myocardial infarction, stroke, transient ischemic attack, unstable angina, coronary artery bypass grafting, or percutaneous coronary intervention.
• Uncontrolled arterial hypertension, defined as systolic blood pressure above 160 mmHg or diastolic blood pressure above 100 mmHg at screening.
• Chronic kidney disease with an estimated glomerular filtration rate below 30 mL/min/1.73 m² using the MDRD or CKD-EPI formula.
• Severe hepatic impairment classified as Child-Pugh class C, or ALT or AST greater than three times the upper limit of normal.
• Active malignancy or history of malignancy within 5 years, except successfully treated basal cell or squamous cell carcinoma of the skin.
• Established HIV infection, active hepatitis B defined as HBsAg positive with detectable HBV DNA, or hepatitis C virus infection.
• History of bariatric surgery or bariatric surgery planned during the study.
• Anorexia nervosa, bulimia nervosa, or binge eating disorder diagnosed or active within the past year.
• Pregnancy or breastfeeding.
• Planning pregnancy during the study.
• Woman of childbearing potential unwilling to use effective contraception.
• Use of weight-loss medication, including orlistat, phentermine, combinations with topiramate, naltrexone-bupropion, or other weight-loss medication within 3 months before screening.
• Use of systemic corticosteroids, excluding inhaled or topical corticosteroids, for more than 2 weeks within 3 months before screening.
• Use of antipsychotic medication associated with significant weight gain unless used at a stable dose for more than 6 months.
• Participation in another interventional clinical study within 30 days before screening.
• Known hypersensitivity to semaglutide or any excipient.
• No smartphone or unwillingness to use digital health technology.
• Severe mental disorder impairing the ability to provide informed consent or comply with the protocol.
• Active alcohol or drug dependence within the past year.
• Any condition that, in the investigator's opinion, may compromise participant safety or the integrity of the study.