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More serious but less common adverse effects include: Pancreatitis : Patients should seek immediate medical attention if they experience severe, persistent abdominal pain that may radiate to the back Diabetic retinopathy complications : Rapid improvement in glycaemic control has been associated with temporary worsening of diabetic retinopathy, particularly in patients with pre-existing retinopathyregular eye screening is recommended [1] [4] Hypoglycaemia : Risk is low when Rybelsus is used alone, but increases when combined with insulin or sulfonylureasdose reduction of these medications may be necessary [2] [4] Acute kidney injury : Reported in association with severe gastrointestinal adverse reactions leading to dehydration Gallbladder disease : Cholelithiasis and cholecystitis have been reportedseek medical attention for symptoms such as right upper abdominal pain, fever, or jaundice [1] [4] Hypersensitivity reactions : Including anaphylaxis and angioedemaseek urgent medical care if symptoms occur Intestinal obstruction/ileus : Rare but seriousseek urgent assessment for severe or persistent abdominal pain with vomiting or marked constipation Important drug interactions: Levothyroxine: Monitor thyroid function tests when co-prescribed Warfarin/acenocoumarol: Consider closer INR monitoring when initiating Rybelsus Other oral medications: Separate by at least 30 minutes due to delayed gastric emptying Regarding potential for misuse , there is no evidence that Rybelsus produces euphoria, psychological dependence, or compulsive drug-seeking behaviour

Proteomics, transcriptomics and histology Proteomics, bulk RNA sequencing and immunofluorescence was performed as described in Supplementary Information 1

To perform a bodyweight squat, stand with your feet shoulder-width apart, engage your core, and lower your body by bending your knees and pushing your hips back