Many obese sufferers also suffer from type 2 diabetes mellitus. The discovery of liraglutide, an antidiabetic drug that is also effective for weight loss, provides new hope for overcoming obesity and diabetes.

Liraglutide for Treatment of Type 2 Diabetes Mellitus and Obesity
Illustration Injecting Saxenda

Of the various antidiabetic drugs, liraglutide is the type that has been studied to promote weight loss. Liraglutide is a glucagon-like peptide-1 (GLP-1) agonist class. GLP-1 is a polypeptide incretin hormone naturally secreted by L cells in the digestive tract when there is a nutritional stimulus. When there is glucose intake, this hormone will stimulate insulin secretion and reduce glucagon concentration in blood plasma to maintain glucose homeostasis. GLP-1 can also slow down the stomach's emptying process, reduce appetite, and increase heart rate. The effects of GLP-1 being studied on promoting weight loss are reducing appetite and slowing gastric emptying.

The natural form of GLP-1 has a very short half-life of fewer than 2 minutes. Therefore, liraglutide (GLP-1 agonist) was developed, which has arginine as a substitute for lysine and palmitic acid chain so that its pharmacokinetic effect is increased. 

Optimal absorption of liraglutide was achieved 11 hours after the subcutaneous injection. The half-life for healthy individuals and people with type 2 diabetes mellitus is 13 hours, so the injection is enough to be done once a day.

Saxenda and Victoza

Victoza was declared safe by the FDA (Food and Drug Administration) in the United States as an adjunct to diet and exercise to manage type 2 diabetes mellitus in 2010. Victoza is available as a subcutaneous injection at a dose of 1.8 mg per day. The results of various controlled trials suggest that GLP-1 agonists can promote weight loss. Therefore, liraglutide was developed and tested for its ability as a weight-loss drug. Several phase III clinical trials of liraglutide have shown satisfactory results.

Saxenda is the newest drug declared safe by the FDA in 2014 for weight management for obese patients with a BMI (Body Mass Index)> 30 kg / m2 or overweight patients with a BMI> 27 kg / m2 has comorbidities—associated with weight.

Contraindications and Side Effects

a. Contraindications for liraglutide are:
  • pregnant and lactating women, 
  • children, 
  • patients using insulin injections or other types of GLP-1 agonists, 
  • and patients who have a personal or familial history of MTC (Medullary Thyroid Carcinoma) or MEN 2 (Multiple Endocrine Neoplasia 2).

b. The most common side effects of liraglutide injection are: 
  • nausea, 
  • vomiting, 
  • dizziness, 
  • diarrhea, 
  • headache, 
  • dyspepsia, 
  • fatigue, 
  • constipation, 
  • and hypoglycemia. 
The most common reason for discontinuation of liraglutide is gastrointestinal problems.

Effects of Liraglutide on Obesity 

a. Effects of Liraglutide on Type 2 Diabetes Mellitus and Obesity
The satiety and clinical adiposity - liraglutide evidence in non-diabetic and diabetic individuals (SCALE) study was conducted on 846 participants with type 2 diabetes mellitus who had a BMI> 27 kg / m2 for 56 weeks and followed by a 12-week drug-free follow-up to see the effect of the injection. Liraglutide against HbA1c levels and weight loss.

Participants were divided into three groups: the 3.0 mg liraglutide injection group, the 1.8 mg liraglutide injection group, and the control group with placebo injection. The study results stated that the proportion of participants who achieved the HbA1c target below 7% came from the 3.0 mg and 1.8 mg liraglutide injection group compared to the control group. In addition, the 3.0 mg and 1.8 mg liraglutide injection groups had a higher mean weight loss compared to the control group, namely 6.0% (6.4 kg), 4.7% (5.0 kg). , and 2% (2.2 kg).

The results above were consistent with a meta-analysis of 25 controlled trials involving more than 6,000 participants. Of the 25 controlled trials, 3 of them tested the effect of injection of GLP-1 agonist (liraglutide or exenatide) on weight loss in obese participants without diabetes mellitus, and other controlled trials tested the effect of injecting GLP-1 agonists (liraglutide or exenatide) on weight loss in obese participants with type 2 diabetes mellitus.

The meta-analysis results state that injection of liraglutide or exenatide triggers weight loss in obese patients with type 2 diabetes mellitus and in obese patients who do not suffer from type 2 diabetes mellitus. In addition, injection of liraglutide with the highest dose (3 mg/day) can also reduce HbA1c levels more when compared to the control group.

b. Effects of Liraglutide for Nondiabetic Obesity Patients
A controlled trial of 564 non-diabetic obese patients with a BMI of 30–40 kg / m2 showed that liraglutide injection-induced greater weight loss than the orlistat group or the control (placebo) group. Side effects, such as nausea and vomiting, were more frequent in the 3.0 mg/day liraglutide injection group. These side effects were tolerable and did not discontinue liraglutide injection before 20 weeks (controlled control trial period).

Comparison of Liraglutide with Other Weight Loss Drugs

Currently, there are four types of weight loss drugs besides liraglutide that have been declared safe by the FDA and can be used for the long term, namely orlistat, lorcaserin, the combination of phentermine/topiramate, and the combination of naltrexone/bupropion with a fixed-dose (fixed-dose combination).

A meta-analysis of the five weight loss drugs showed that liraglutide injection could achieve a weight loss of 5% in the first year compared with lorcaserin or orlistat. The ability of liraglutide injection to lose weight is equivalent to the combination of naltrexone/bupropion and slightly lower than the combination of phentermine/topiramate.

Compared to other weight-loss drugs, the price of liraglutide (which is not currently available in generic form) in the market is much expensive. Liraglutide is also only available as an injection, so its administration is more difficult than other weight loss drugs taken orally. In addition, the administration of liraglutide should be carried out in a gradual dose, namely 0.6 mg once a day for 1 week, then increased to 1.2 mg/day (1 injection) for 1 week, then increased to 1.8 mg/day. day (1 injection). The maximum dose of Victoza is 1.8 mg/day, while the maximum dose of Saxenda is 3 mg/day (which must be achieved gradually over 5 weeks).

The antidiabetic drug liraglutide, a GLP-1 agonist class, has a good ability to reduce HbA1c levels in type 2 diabetes mellitus sufferers and trigger weight loss in obese patients, both those with type 2 diabetes mellitus and those without type 2 diabetes mellitus. it has been declared safe by the FDA to treat type 2 diabetes mellitus and obesity. Liraglutide is only available in injection form, and there is no generic version available yet. There was no difference in the dosage of liraglutide in obese patients with type 2 diabetes mellitus or non-diabetic obese patients.

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