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GLP-1 receptor agonists

Injectable agents structurally similar to endogenous GLP-1.

Activate GLP-1 receptors in many issues, that may delay gastric emptying, promote appetite suppression, and typically result in weight loss approximately 2-4 kg.

Only about 27% of patients prescribed GLP –1 agonists were adherent after one year.

Produce weight loss of 12 to 18%, exceeding any prior pharmacological therapy.

Weight loss plateaus by 12 to 18 months. .

If the drug is stopped the patients generally regain their lost weight within a year.

GLP – 1 agonism has broad effects: redistributes, fat, decrease, inflammation, inhibits, glucagon, production, and delays gastric emptying.

Include exenatide, semaglutide,albiglutide and dulaglutide, tirezpide, and liraglutide.

Stabilize post meal glucagon and help return blood glucose to normal.

A1c reduction typically ranges from 0.5% to 2% and can be accompanied by weight loss of typically 2 to 3 kg.

Effects on receptors include increased satiety, decreased gastric emptying, increase glucose uptake by muscle and adipose tissue, decreased glucose production by the liver, and increase insulin secretion.

The effect of GLP-1 on insulin secretion is glucose dependent, and therefore does not lead to hypoglycemia if glucose levels are low.

Once released, GLP-1 is metabolized by dipepidyl peptidase 4 (DPP-4) shortly thereafter.

GLP-1 analogues are ideal message of glycemic controlling combat many of the negative consequences of type two diabetes.

Decrease his hemoglobin A-1 C levels by 0.3%-1.4%, reduce body fat, and induces a small reduction in blood pressure and increase in heart rate.

These agents typically do not cause hypoglycemia, although caution is taken in the setting of multiple glucose lowering therapies.

Gastrointestinal side effects are common.

The most common adverse events are a G.I. issues, including nausea, vomiting, diarrhea, and constipation.

Recent findings found increased risk for pancreatitis, bowel obstruction, gastroparesis biliary disease, gallstones, lung aspiration with anesthesia.

Some patients cannot tolerate these agents.

They have a higher incidence of pancreatitis and decision should be avoided in patients with history of medullary thyroid cancer or a family history of multiple endocrine neoplasia 2 syndrome due to concern for increase risk of C cell thyroid tumors.

This study found that use of GLP-1 agonists for weight loss compared with use of bupropion-naltrexone was associated with increased risk of pancreatitis, gastroparesis, and bowel obstruction but not biliary disease.

The treatment of diabetes with GLP-1 receptor agonists is associated with a reduction of more than 50% in the risk of new onset Parkinson’s disease.

In the LEADER study metformin and GLP1RA agents should be added in obese patients because of the potential to promote weight loss.

It is now recommended by the ADA to be the first injectable agent prior to the use of insulin.

In the PIONEER 3 trial Semaglutide, the first oral preparation of a GLP-1RA, resulting in greater glucose lowering and weight loss compared with sitagliptin.

The mechanism of which GLP-1 RAs affect cardiovascular disease or more variable in those with SGLT2 inhibitors.

GLP-1 agonists are injectable agents used a second line therapies to treat type two diabetes.

GLP-1 receptor receptors are widely expressed, particularly in the brain.

GLP-1 increases satiety decreases gastric emptying and has a direct effect on adipocytes as well as cardiovascular tissue and bone.

Daily oral orfoglipon a non-peptide GLP-1 receptor agonist is associated with weight reduction and adverse events similar to injectable GLP-1 receptor agonists.

Weight loss with these agents associated with a 25% weight loss in lean body mass.

With discontinuation of these weight loss agents, patients  regain weight primarily as fat.

GLP-1 receptor agonists are more effective in female patients.

List prices range from $12-$16,000 per year and even with maximum negotiated discounts, costs  will likely exceed $6500 per year.

 

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