Caution!: Semaglutide drug also known as Wegovy or Ozempic (for weight loss) may have side effects that you must be made aware of before taking it; discuss with your doctor; active living, moderation

by Paul Alexander

Note, Ozempic was marketed to improve blood sugar in people with Type 2 diabetes; these are GLP-1 receptor (Glucagon-like peptide-1 (GLP-1)) agonists; always healthier life styles, common sense

‘Among them, semaglutide with once-daily oral dosage form (brand name: Rybelsus®) and once-weekly subcutaneous injectable formulation (brand names: Ozempic® and Wegovy®) have shown a superiority in weight management with expected annual sales beyond $10 billion3. While their efficacies and safety profiles are widely accepted, long-term adverse events such as increased risk of intestinal obstruction have been reported in diabetic patients, which is 4.5 times higher than those receiving other glucose control medications4. A real-world study of 25,617 subjects demonstrated a 3.5-fold increase in the intestinal obstruction rate associated with GLP-1RA treatment5.


Experimentally, one-month regimen of exenatide in rats increased the length and weight of the small intestine by 9% and 31%, respectively6, consistent with our own observations that the rats had an average increase of 43% in the small intestine length after 3-month treatment of polyethylene glycol (PEG)-exenatide (data not shown). Dapiglutide was shown to dose-dependently increase the size (by >20%) of the bowel in mice7 and promoted the height of the small intestinal mucosa by 34%8. Because GLP-1RAs could cause continuous increases in the intestinal length and villus height, the small intestine may become as inelastic and fibrotic as a loose spring (Fig. 1), leading to long-term upper intestinal obstruction, probably due to certain unexpected off-target effects9 associated with: (i) use of doses far beyond the physiological level of GLP-1; (ii) much longer half-lives of GLP-1RAs (6–24 h) than that of native GLP-1 (1–2 min); and (iii) GLP-1 and glucagon-like peptide-2 (GLP-2) are simultaneously secreted in equal amounts under normal conditions. Long-term application of GLP-1RAs may also elevate the release of endogenous GLP-2, which is a cell-specific growth hormone regulating the growth of the small intestine, colonic villi and crypts, increasing the length and weight of the small intestine, and reducing antral motility. Teduglutide, a GLP-2 analog, was approved for the treatment of short bowel syndrome (SBS) and intestinal failure10.’

‘It is possible to observe a high prevalence of gastrointestinal disorders (N = 3502, 53.2%). The most severe reported cases were primarily gastrointestinal disorders, metabolic, and nutritional disorders, eye disorders, renal and urinary disorders and cardiac disorders, with an evident higher prevalence of adverse gastrointestinal events both in oral and injectable dosage form (N = 133, 50.0% vs N = 588, 47.2%, respectively). Through a comparative analysis, semaglutide had a greater number of reported gastrointestinal adverse events compared to sitagliptin and empaglifozin (p < 0.00001).’

Case reports of acute kidney injury in patients taking the glucagon-like peptide 1 (GLP-1) receptor agonists exenatide and liraglutide have been reported. We report 2 patients with chronic kidney disease due to diabetic kidney disease who experienced rapid worsening of kidney function and increased proteinuria after being prescribed the GLP-1 receptor agonist semaglutide. In 1 patient, kidney biopsy showed advanced diffuse and nodular glomerulosclerosis accompanied by interstitial lymphoplasmacytic and eosinophilic infiltrate and evidence of acute tubular injury. At this time, the long-term outcomes of patients who experience acute kidney injury associated with GLP-1 receptor agonists is not known. We recommend that caution be used with these agents in patients with moderate to severe chronic kidney disease due to limited kidney reserve in the event of an adverse kidney event. Because most adverse kidney events have occurred in patients who experience adverse gastrointestinal symptoms, such patients should have laboratory tests and discontinuation of the medication if there is acute worsening of kidney function.’