Saxenda is not working for me

Awesomizer06 wrote: »

I seem to be the only one which Saxenda did not work. No side effects, no appetite suppression, no weight loss. I'm very frustrated.
Did you or anyone you know has the same experience?

Weight loss depends on your energy balance (calories in, calories out). From what I understand, Liraglutide - and other GLP-1 agonists - don't result in weight loss by themselves. They do help by suppressing your hunger, thus making your planned calorie deficit easier to bear. If you don't eat less than you burn, no medication can really help you.

If you don't see any result as far as your appetite is concerned, and you don't have a diabetes problem, then talk to your doctor about stopping using it. Personally, I've been prescribed Victoza for five months now (at a lower dose for diabetes prevention), and I think it helps, although I haven't made any changes to my planned diet due to it.

psychod787 wrote: »

Yes it is a GLP-1 agonist. GLP-1 is a satiety hormone. I would suggest that there are more natural ways of boosting GLP-1. First, increase of lean protein. Protein increases the release of GLP-1 which might be one of the reasons high protein diets are affective. The second, is increase consumption of whole fruits and vegetables. Fiber also seems to increase GLP-1. JMHO oh, will post research links if requested......

The problem is that GLP-1 itself is not stable in the blood long enough to do its job with regards to daily satiety (it gets catalyzed by DPP4 far too quickly). So, any natural way is pretty irrelevant/limited for the application we are talking about. Liraglutide stays in the blood for 24 hours. And Semaglutide (coming to market now here in Europe) stays in the blood for a week.

Having said that, it is always a good idea to incorporate lean protein, dietary fiber, fruits and vegetables to our nutrition. Especially since they a priori are very filling foods too!

psychod787 wrote: »

link requested.......

Ok:

Degradation.
https://en.wikipedia.org/wiki/Glucagon-like_peptide-1#Degradation

Once secreted, GLP-1 is extremely susceptible to the catalytic activity of the proteolytic enzyme dipeptidyl peptidase-4 (DPP-4). Specifically, DPP-4 cleaves the peptide bond between Ala8-Glu9 resulting in the abundant GLP-1 (9–36) amide constituting 60–80 % of total GLP-1 in circulation. DPP-4 is widely expressed in multiple tissues and cell types and exists in both a membrane-anchored and soluble circulating form. Notably, DPP-4 is expressed on the surface of endothelial cells, including those located directly adjacent to GLP-1 secretion sites.[2] Consequently, less than 25% of secreted GLP-1 is estimated to leave the gut intact. Additionally, presumably due to the high concentration of DPP-4 found on hepatocytes, 40–50% of the remaining active GLP-1 is degraded across the liver. Conclusively, only 10–15 % of secreted GLP-1 reaches circulation intact due to the activity of DPP-4.[3]

Neutral endopeptidase 24.11 (NEP 24.11) is a membrane-bound zinc metallopeptidase widely expressed in several tissues, but found in particularly high concentrations in the kidneys, which is also identified accountable for the rapid degradation of GLP-1. It primarily cleaves peptides at the N-terminal side of aromatic amino acids or hydrophobic amino acids and is estimated to contribute by up to 50% of the GLP-1 degradation. However, the activity only becomes apparent once the degradation of DPP-4 has been prevented, as the majority of GLP-1 reaching the kidneys have already been processed by DPP-4. Similarly, renal clearance appear more significant for the elimination of already inactivated GLP-1.[6]

The resulting half-life of active GLP-1 is approximately 2 minutes, which is however sufficient to activate GLP-1 receptors.

Endogenous GLP-1 half life and Liraglutide Pharmacokinetics.
https://en.wikipedia.org/wiki/Liraglutide#Pharmacokinetics

Endogenous GLP-1 has a plasma half-life of 1.5–2 minutes due to degradation by the ubiquitous enzymes, dipeptidyl peptidase-4 (DPP4) and neutral endopeptidases (NEP). The half-life after intramuscular injection is approximately half an hour, so even administered this way, it has limited use as a therapeutic agent. The metabolically active forms of GLP-1 are the endogenous GLP-1-(7-36)NH2 and the more rare GLP-1-(7-37). The prolonged action of liraglutide is achieved by attaching a fatty acid molecule at one position of the GLP-1-(7-37) molecule, enabling it to both self-associate and bind to albumin within the subcutaneous tissue and bloodstream. The active GLP-1 is then released from albumin at a slow, consistent rate. Albumin binding also results in slower degradation and reduced renal elimination compared to that of GLP-1-(7-37).[15]

....

It is essentially the main reason for GLP-1 receptor agonists to exist in the first place.

Dante_80 wrote: »

psychod787 wrote: »

link requested.......

Ok:

Degradation.
https://en.wikipedia.org/wiki/Glucagon-like_peptide-1#Degradation

Once secreted, GLP-1 is extremely susceptible to the catalytic activity of the proteolytic enzyme dipeptidyl peptidase-4 (DPP-4). Specifically, DPP-4 cleaves the peptide bond between Ala8-Glu9 resulting in the abundant GLP-1 (9–36) amide constituting 60–80 % of total GLP-1 in circulation. DPP-4 is widely expressed in multiple tissues and cell types and exists in both a membrane-anchored and soluble circulating form. Notably, DPP-4 is expressed on the surface of endothelial cells, including those located directly adjacent to GLP-1 secretion sites.[2] Consequently, less than 25% of secreted GLP-1 is estimated to leave the gut intact. Additionally, presumably due to the high concentration of DPP-4 found on hepatocytes, 40–50% of the remaining active GLP-1 is degraded across the liver. Conclusively, only 10–15 % of secreted GLP-1 reaches circulation intact due to the activity of DPP-4.[3]

Neutral endopeptidase 24.11 (NEP 24.11) is a membrane-bound zinc metallopeptidase widely expressed in several tissues, but found in particularly high concentrations in the kidneys, which is also identified accountable for the rapid degradation of GLP-1. It primarily cleaves peptides at the N-terminal side of aromatic amino acids or hydrophobic amino acids and is estimated to contribute by up to 50% of the GLP-1 degradation. However, the activity only becomes apparent once the degradation of DPP-4 has been prevented, as the majority of GLP-1 reaching the kidneys have already been processed by DPP-4. Similarly, renal clearance appear more significant for the elimination of already inactivated GLP-1.[6]

The resulting half-life of active GLP-1 is approximately 2 minutes, which is however sufficient to activate GLP-1 receptors.

Endogenous GLP-1 half life and Liraglutide Pharmacokinetics.
https://en.wikipedia.org/wiki/Liraglutide#Pharmacokinetics

Endogenous GLP-1 has a plasma half-life of 1.5–2 minutes due to degradation by the ubiquitous enzymes, dipeptidyl peptidase-4 (DPP4) and neutral endopeptidases (NEP). The half-life after intramuscular injection is approximately half an hour, so even administered this way, it has limited use as a therapeutic agent. The metabolically active forms of GLP-1 are the endogenous GLP-1-(7-36)NH2 and the more rare GLP-1-(7-37). The prolonged action of liraglutide is achieved by attaching a fatty acid molecule at one position of the GLP-1-(7-37) molecule, enabling it to both self-associate and bind to albumin within the subcutaneous tissue and bloodstream. The active GLP-1 is then released from albumin at a slow, consistent rate. Albumin binding also results in slower degradation and reduced renal elimination compared to that of GLP-1-(7-37).[15]

....

It is essentially the main reason for GLP-1 receptor agonists to exist in the first place.

thanks for the info. It will take me a while to unpack and digest the info.