Glp for Weight loss. There are a number of topics that can make people interested in losing weight. More and more people are beginning to wonder about the whole program as well as its effectiveness. Although many of us don’t like to think about it, obesity is a huge problem in the
GLP-1 Agonists for Type 2 Diabetes
GLP-1 receptor agonists are a type of non-insulin medication that is used in combination with diet and exercise to help treat type 2 diabetes. These drugs are prescribed to help lower blood glucose levels and hemoglobin A1C and to aid in weight loss. Research has shown that GLP-1 receptor agonists can have other health benefits on blood pressure, cholesterol levels, and beta-cell function.1
These injectable drugs are usually prescribed along with oral diabetes medicines or insulin therapy. They aren’t regarded as first-line treatment in diabetes, but they can be a valuable part of the overall management plan.
Type 2 Diabetes Doctor Discussion Guide
How Insulin Works and Why You Need It
How They Work
Glucagon-like peptide (GLP-1) is a type of hormone known as an incretin that’s lower than normal in type 2 diabetes. GLP-1 receptor agonists belong to a class of medications known as incretin mimetics.
By mimicking the effects of GLP-1, the GLP-1 receptor agonists have many effects.
Some of their actions include:
- Help control appetite and blood sugar levels
- Help the pancreas release the optimal amount of insulin, which transports glucose (sugar) to tissues in the body where it can be used for energy2
- Slow the rate at which food leaves the stomach, which helps to control post-prandial (after-meal) blood sugar levels
GLP-1 agonists work on different organs throughout the body.
GLP-1 sends a signal to the hypothalamus, the part of the brain responsible for appetite and thirst, to take in less water and food. This can lead to weight loss.
Because GLP-1 receptor agonists dampen thirst, it’s vital to drink plenty of water and other fluids to stay hydrated while taking these medications.
GLP-1 stimulates gluconeogenesis, which is the process the body uses to make glucose from protein or fat. This process lowers blood sugar by stimulating glucose uptake into the cells and increasing how efficiently the body uses insulin.
When GLP-1 encounters glucose, the pancreas is triggered to secrete more insulin, which lowers the amount of post-meal glucose in the blood.
GLP-1 also decreases the secretion of glucagon-a pancreatic hormone that helps to prevent blood sugar levels from dipping too low. In people with type 2 diabetes, glucagon can cause blood glucose levels to become too high.
GLP-1 lowers hepatic (liver) glucose output, which helps lower blood sugar levels.
As gluconeogenesis increases, glucagon receptors are reduced in the liver, inhibiting glucose formation and stimulating glucose uptake by cells, thus lowering the amount of glucose in the blood.
GLP-1 decreases both the secretion of acid in the stomach and how quickly food is emptied from the stomach, prolonging the sensation of fullness. This can limit how much a person eats and may ultimately lead to weight loss.2
What Can We Learn From GLP-1 Receptor Agonist Studies on Weight Loss?
Is weight loss with GLP-1 receptor agonists permanent? Can they be used in binge eating disorder or after bariatric surgery? In this commentary, I answer these and other questions from learners who participated in the webinar, “Ushering in a New Era of Sustainable Weight Loss With Incretin-Based Therapies.”
Is weight loss sustained after stopping treatment with a GLP-1 receptor agonist?
Unfortunately, the weight loss benefit of GLP-1 receptor agonists does go away when you stop the medication. Patients can regain some or all of the weight they lose.
The STEP 4 withdrawal trial compared the effect on body weight of continuing once-weekly treatment with subcutaneous semaglutide (2.4 mg) vs switching to placebo (both with lifestyle intervention) in adults with overweight or obesity.
After a 20-week run-in period with a mean weight loss of 10.6%, participants who were randomized to continue semaglutide for 48 more weeks continued to lose weight (-7.9%), whereas those randomized to switch to placebo gradually regained 6.9% of the weight between Week 20 and Week 68.
These results are similar to results from the follow-up phase of the SCALE Maintenance trial of liraglutide vs placebo (both with lifestyle intervention), where participants lost weight during the 56-week treatment phase but then regained some weight during the 12-week post-drug discontinuation follow-up.
What do these semaglutide and liraglutide trial results tell us? They tell us that obesity is a chronic disease. We should look at obesity treatment the same way we look at hypertension or hyperlipidemia treatment. If you stop taking antihypertensive medications, your blood pressure will go up again; if you stop taking a GLP-1 receptor agonist, your weight will go up again.
How long can we treat patients with liraglutide for weight loss?
Although the double-blind period of the SCALE Maintenance trial was 56 weeks, the longer 3-year evaluation in the SCALE Obesity and Prediabetes trial showed that liraglutide was more effective than placebo in reducing type 2 diabetes risk and body weight in individuals with obesity and prediabetes. However, only 50% of participants completed the study up to Week 160.
Whereas data demonstrating long-term (>3 years) benefits of sustained weight loss are scant, ongoing monitoring of weight loss responses and adverse events is necessary to determine the optimal treatment duration for individual patients.
Regardless of how long treatment lasts, weight loss pharmacotherapy should be considered as an adjunct therapy to lifestyle modification. Liraglutide is approved by the FDA for chronic weight management along with a reduced calorie diet and increased physical activity.
Oxyntomodulin, a Natural GLP-1 and Glucagon Co-Agonist
The journey to discovery of the glucagon family of peptides and an endogenous GLP-1/glucagon co-agonist, oxyntomodulin (OXM) is an example of a concerted effort from many dedicated research groups. A pivotal point early on in this research was the use of the known peptide sequence of glucagon to facilitate the discovery of other
glucagon-like peptides' in the gastrointestinal tract with the help of the radioimmunoassay method . The search forglucagon-like reactivity (GLI)’ in the gut revealed a partial peptide sequence for a peptide named
Glicentin', later to be fully characterised as a 69-amino acid peptide containing a 30-amino acidGlicentin-related pancreatic polypeptide’ (GRPP), the full sequence of glucagon, and an 8-amino acid c-terminal extension . The 8-amino acid extended glucagon fragment,
Glucagon-37' was isolated from porcine jejuno-ileum, characterised and shown to be the bioactiveenteroglucagon’ due to its ability to bind to and stimulate glucagon receptors in liver membrane extracts . Due to the potent effect on oxyntic cell signalling, bioactive enteroglucagon/Glucagon-37 was named oxyntomodulin . As the primary structure of glicentin was discovered, evidence also emerged for post-translational processing of proglucagon to form glucagon and glicentin related pancreatic peptide, secreted `synchronously’ from the pancreatic alpha cell . Beyond the protein-based methodologies used to characterise glicentin, GRPP and oxyntomodulin, the increased capability to sequence genes at the time led to the first sequence of mammalian preproglucagon . This revealed two further glucagon-like polypeptides, now known as GLP-1 and GLP-2, and confirmed earlier reports suggesting that the MW of proglucagon is much larger than that of glicentin alone . The post-translational processing of pro-glucagon is now known to be differentially regulated in pancreas and gut . Alternative processing of proglucagon leads to the formation of glucagon, GRPP and major pro-glucagon fragment (MPGF) in the pancreas, whereas in the gut and brain glicentin, GRPP, oxyntomodulin, GLP-1 and GLP-2 are formed (Figure 1). The endogenous gut hormone oxyntomodulin is therefore formed through specific splicing of the proglucagon gene and includes the full sequence of glucagon along with the 8-amino acid sequence named IP-1. This process occurs in the intestinal L cells of the gastrointestinal tract leading to the co-secretion of GLP-1 and oxyntomodulin in response to nutrient sensing