re: 4 year long study on Wegovy/semaglutide shows heart benefits and safety

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I didn’t know about ddp4. There are drugs that suppress this enzyme, but it doesn't look like it leads to weight loss. I asked chat GPT if there were certain foods that increased this enzyme- “ Yes, certain foods can increase the activity of DPP-4. Foods high in protein, such as meat, fish, eggs, and dairy products, can stimulate the release of DPP-4. Additionally, high-fat meals have been shown to increase DPP-4 activity.” I’ll have to look at those links you posted.

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3. DPP-4 and diabetes:
In T2D patients, insulin resistance leads to higher blood glucose levels and a higher level of activated incretins may reverse the increased glucose level in blood. Incretins are a group of metabolic hormones, which decrease blood glucose levels by inducing insulin hormone production from pancreatic ß cells and inhibiting glucagon secretion. Glucagon-like peptide-1 and -2 (GLP-1 and -2), and glucose-dependent insulinotropic peptide (GIP) are examples of incretins [45]. By 1990s, DPP-4 and its association with diabetes came into the light where it was observed that DPP-4 is involved in initial degradation of incretins and thus the proposition to block DPP-4 activity to restore incretin functions become evident [46]. Deacon et al. observed that DPP-4 was a major, if not the only, route for the regulation of GLP-1as DPP-4 inhibitor valine-pyrrolidine treatment could not completely but partially prevented degradation of exogenous GLP-1 in pig [47]. The same group of scientists also noted a similar finding for GIP [48]. Administration of another DPP-4 inhibitor, ile-thiazolidide increased circulating incretins as well as insulin secretion in rats [49]. These studies together establish some preclinical bases of the hypothesis that inhibiting DPP-4 activity leads to increased circulating GLP-1 that can restore insulin secretion and regulate blood glucose levels in T2D patients. After several years of the initial hypothesis was launched [47], a 4-weeks clinical trial was conducted, and the results of this short-term administration of DPP-4 inhibitor was published for the first time in 2002 [50]. Subsequently, a clinical trial spanning one year was performed, and the anti-diabetic effects of sustained DPP-4 inhibitor vildagliptin were suggested [51].

Those early results were soon followed by numerous experimental as well as clinical studies. In 2006, DPP-4 inhibitor sitagliptin was approved as a drug to control blood glucose level in T2D patients. Nowadays, DPP-4 inhibitors are well-recognized medicines that are used to reduce hyperglycemia in T2D patients, and two types of DPP-4 inhibitors are used clinically worldwide. There are DPP-4 structure mimetic and non-peptidomimetics. In 2006, the FDA approved the very first type of DPP-4 inhibitors, which are structural mimetics. Sitagliptin, vildagliptin, and saxagliptin are examples of this first type of inhibitors. FDA approved first non-peptidomimetic inhibitors in 2011. Alogliptin and linagliptin are examples of the second type of DPP-4 inhibitors, non-peptidomimetics. Almost all clinical studies have shown reduced glycated haemoglobin % (HbA1c%) and fasting blood glucose (FBG) level in T2D patients with different types of DPP-4 inhibitors administration such as sitagliptin [52, 53], vildagliptin [54, 55], linagliptin [56], saxagliptin [57, 58].

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Safe and convenient methods to prevent diseases, especially chronic and metabolic disorders such as T2DM, hypertension, etc., are widely sought. Diets rich in specific bioactive ingredients, including food protein-derived peptides, have potential application in the prevention and management of T2DM. Food-derived peptides may be a complementary strategy to help regulate glycemia in diabetic or prediabetic individuals. Thus, it is necessary to find clinical evidence of the effect of food-derived peptides in regulating blood glucose. It is also necessary to develop powerful strategies by which to discover more food-derived DPP-IV inhibitory ingredients, not only purified active peptides, but hydrolysates or peptide mixtures, which may show greater safety and potency.

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