Dr. Ahmed
GLP-1 analogs are among the best currently available weight loss medicines. However, only two of the GLP-1 analogs have been approved for the treatment of weight loss.
In addition to weight loss, GLP-1 analogs are also best for lowering blood glucose. However, they are only recommended for use in patients with Type 2 Diabetes Mellitus.
Depending on the GLP-1 medicine you use and the dosage, weight loss may vary. According to research, all GLP-1 medications can cause users to lose between 4.8 and 7.2 kilos (10.5 to 15.8 pounds) of weight.
According to studies, those who used Semaglutide and changed their lifestyles lost roughly 33.7 pounds (15.3 kilograms) as opposed to 5.7 pounds (2.6 kilograms) among those who didn’t.
Most GLP-1 agonists are administered subcutaneously into the skin once daily or once weekly.
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Why do people gain weight?
While it is generally accepted that weight gain results from an imbalance between caloric intake and caloric expenditure, environmental and genetic factors are also linked to the risk of being obese.
More than 140 chromosomal areas with a genetic link to obesity have been found using data from the genome project.
Weight gain is also linked to the use of some medications, such as antidepressants and corticosteroids, as well as conditions like Cushing’s disease and hypothyroidism [ref].
According to GI system research, a changed microbiota may potentially contribute to the emergence of obesity [ref].
How do GLP-1 agonists help you lose weight?
Glucagon-like peptide-1 receptor agonists increase insulin secretion from the beta-pancreatic cells while decreasing glucagon release from the alpha-pancreatic cells to enhance glycemic control [ref].
In addition, GLP-1 agonists decrease stomach emptying, boost satiety, and suppress appetite, all of which help people lose weight.
Dipeptidyl peptidase IV breaks down endogenous GLP-1 quickly, causing it to have a half-life of fewer than 2 minutes (DPP4) [ref].
In addition, to the direct effects of GLP-1 agonists on the stomach, it also sends a signal to the brain’s satiety center. This reduces the person’s cravings for foods that have a high glycemic index and are high in calories.
When the satiety center in the brain is stimulated, you will not feel like eating. Your stomach will be full as if you have just had a meal.
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How are GLP-1 agonists classified?
Glucagon-like peptide-1 receptors (GLP-1 agonists) are classified as: [ref]
- Short-acting agent
- Long-acting agent
Short-acting agent | Long-acting agent |
| Short-acting agonists circulate for a few hours, accompanied by intervals of GLP-1 inactivity. | Long-acting agonists result in a stable drug concentration over a long period of time. |
| Short-acting GLP-1 agonists decrease blood sugar levels by decreasing gastric emptying | Long-acting GLP-1 agonists lower glucose levels by slowing stomach emptying, boosting insulin secretion, and blocking glucagon. |
| Short-acting medications are not yet authorized for use in weight loss. These include:
| Except for Trulicity (Dulaglutide), two of the long-acting GLP-1 analogs are FDA-approved for weight loss. These include:
|
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Obesity Treatment with GLP-1 Receptor Agonists
The medications Liraglutide (Victoza) and Semaglutide (Ozempic) are presently accepted for the treatment of type 2 diabetes.
Both drugs, sold under the trade names Saxenda and Wegovy, are also approved as supplements to calorie restriction and increased activity for the management of obesity [ref].
Liraglutide (Saxenda) for weight loss:
Liraglutide (3 mg) was the first GLP-1 agonist to receive FDA approval in 2015 for the chronic management of weight in individuals with obesity and/or overweight.
The FDA authorized an amended label for liraglutide’s use in treating teenage obesity in December 2020. (12-17 years).
The target dose is 3 mg once daily, while the beginning dosage is 0.6 mg once daily for 1 week. Liraglutide is a long-acting medication that is injected under the skin every day. Its half-life is 12.6 to 14.3 hours [ref].
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Semaglutide for weight loss:
The FDA authorized Semaglutide in June 2021 for the chronic management of weight in persons who are obese and overweight.
The once-weekly subcutaneous injection should start at 0.25 mg and be escalated to 2.4 mg over four weeks.
Semaglutide can be administered once a week because of its prolonged half-life of roughly one week [ref].
Liraglutide and Semaglutide’s effectiveness for weight loss:
- Liraglutide and Semaglutide were evaluated in persons without diabetes and with a BMI under 30 (mean BMI, 39.3).
- Liraglutide 3.0 daily was related to an estimated mean weight loss of 7.8% at week 52, according to the authors, who also stated that the drug maker supported the trial.
- Semaglutide 0.2 mg, 0.3 mg, and 0.4 mg caused weight losses of 11.6%, 11.2%, and 13.8%, respectively. The estimated mean weight loss for the placebo group was 2.3%.
- The weight loss shown with Semaglutide is more than that seen with orlistat (6%), lorcaserin (6%), phentermine-topiramate (8%–10%), and naltrexone-bupropion (5%), which are all approved antiobesity drugs [ref].
| Semaglutide vs other FDA-approved weight loss drugs | Percent weight loss with Semaglutide greater than the FDA-approved obesity drugs |
| Orlistat | 6% more weight loss Vs orlistat |
| Lorcaserin | 6% more weight loss vs Lorcaserin |
| Phentermine/ Topiramate (Qsymia) | 8 – 10% more weight loss Vs Qsymia |
| Naltrexone/ Bupropion (Contrave) | 5% more weight loss vs Contrave |
- According to the majority of accepted criteria, significant weight loss is defined as a reduction of 5% to 10% of one’s starting weight followed by an improvement in cardiovascular risk factors.
- Once-weekly administration has been shown to improve patient compliance and quality of life over once-daily dosing in the management of GLP-1 receptor agonists in the treatment of type 2 diabetes, as well as the administration of medications for other chronic diseases.
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Safety Concerns and Potential Side Effects of GLP-1:
The disadvantage of GLP-1 drugs is that all but one (Rybelsus) must be administered via injection. And, as with any drug, there is the possibility of serious side effects.
More common side effects usually improve after a while of taking the drug.
- The most frequent side effects of GLP-1 agonists were [ref]:
- vomiting,
- diarrhea,
- constipation,
- abdominal pain,
- headaches,
- fatigue,
- dyspepsia,
- dizziness,
- abdominal distension/pain,
- injection site reactions with Liraglutide,
- increased lipase with Liraglutide,
- pyrexia with Liraglutide,
- eructation with Semaglutide,
- flatulence with Semaglutide,
- Hypoglycemia in patients (Semaglutide)
Hypoglycemia, a more serious danger associated with the GLP-1 class of medications, is low blood sugar.
However, the danger of low blood sugar levels frequently only increases if you’re also taking another medication at the same time that is known to reduce blood sugar, such as sulfonylureas or insulin.
The majority of reported adverse events were mild (69%) while serious adverse events were uncommon.
Only a small number of patients discontinued their prescriptions due to drug-related side effects, and those who did cite GI-related occurrences.
Semaglutide and Liraglutide are examples of GLP-1 receptor agonists that have been used to treat patients who have developed acute pancreatitis and acute gallbladder disease.
Across the Semaglutide dose range (2%-7%), reports of cholelithiasis and cholecystitis increased. The usage of GLP-1 agonists has been linked to an increased risk of getting upper respiratory infections.
Although the higher risk is mentioned as an adverse response in some package inserts of this class, it is not a warning or precaution and is not a reason to avoid using the product [ref].
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