Page 15 - IMO-2-2

Innovative Medicines & Omics Pharmacotherapy of obesity

glyceride that are absorbed. Orlistat can also remove initiated with a low dose (0.6 mg/day) for the first week.
triacylglycerol from the body directly, with consequently Then the dose is increased weekly to 1.2, 1.8, 2.4 mg/day,
reduced caloric intake or weight control. 55 and up to 3 mg/day. If there is intolerance, dose titration
In adults, the recommended dose of orlistat is one 120 mg may be slower, and maximum tolerated dose may be
capsule with each main meal. The capsules may be taken continued if weight loss is maintained. 60
immediately before, during, or up to 1 h after the meal. The Gastrointestinal side effects such as nausea and/or
patient should be on a well-balanced, mildly hypocaloric vomiting are common with liraglutide. Weight-reducing
diet that contains approximately 30% of calories from fat. effect is partially due to suppression of appetite. These side
The daily intake of fat, carbohydrate, and protein should be effects may be transient, and diminish over time. Diarrhea,
distributed as evenly as possible over three main meals. 56 anorexia, and low blood sugar also may be observed. Less
Gastrointestinal adverse effects associated with orlistat, common side effects are renal impairment, gallbladder
include oily stools, diarrhea, abdominal discomfort, disease, or pancreatitis. 61
and fecal incontinence. Symptoms are usually mild-to- Pregnancy, breastfeeding, personal or family history
moderate. There have been rare post-marketing reports of multiple endocrine neoplasia (MEN) 2A or 2B or
of severe hepatic adverse events with orlistat, including medullary thyroid cancer, or previous hypersensitivity
cholestasis and liver failure. While orlistat seems to have to liraglutide are contraindications to liraglutide use. To
positive effects regarding non-alcoholic fatty liver disease, avoid hypoglycemia in patients using insulin secretagogue
the benefits it elicits through weight loss exert a favorable or insulin, dose reduction in these drugs may be necessary
effect on blood pressure. Some of the studies found that if liraglutide is added to the treatment. 62
orlistat has no effect on calcium, magnesium, and iron
balance, with no effects on bone health markers either. 11.3. Topiramate-phentermine
Nevertheless, orlistat administration can be associated Topiramate’s (2,3:4,5-bis-O-(1-methylethylidene)-β-
with acute kidney injury in exceptional cases due to fat D-fructopyranose sulfamate) multifaceted weight loss
malabsorption promoting enhanced oxalate absorption processes include blocking voltage-gated sodium and
that subsequently leads to kidney stones. On the other calcium channels, which are involved in appetite regulation
hand, the agent is known for its carbohydrate metabolism and brain signaling. Enhancement of gamma-aminobutyric
improvement. Importantly, orlistat is also associated with acid receptors, a neurotransmitter that mediates a soothing
interfering with a number of other drugs absorption. effect on the brain, results in a decrease in hunger and
Furthermore, orlistat utilization would suppress the curbing of food cravings. Topiramate acts by blocking
bioavailability of fat-soluble vitamins, necessitating specific glutamate receptors, known to be involved in the
supplementation in consumers to address this issue. 57 excitatory activity of the brain, further helping to curb
Orlistat should not be used in the presence of chronic appetite. The drug further inhibits carbonic anhydrase, an
malabsorption syndrome, cholestasis, pregnancy, and enzyme that intervenes in fat storage; this might reduce
breastfeeding, or in patients with a previous history of the accumulation of adipose tissue. These combined effects
calcium-oxalate stones. 58 on appetite control, fat metabolism, and neural activity
contribute to its weight-reducing properties, which make
11.2. Liraglutide it an effective option in patients with obesity, especially
Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor when combined with phentermine. On account of its wide
agonist, which is also known as incretin mimetics. It action on the nervous system, topiramate has adverse
works by increasing insulin release from the pancreas and effects including tingling, cognitive disturbances, and
decreases excessive glucagon release. Moreover, liraglutide dizziness, thus prompting careful monitoring by health
reduces food intake and causes weight loss through actions practitioners. 63
on both peripheral and central pathways by stimulating Topiramate and phentermine (2-methyl-1-
the hindbrain and hypothalamus. Consequently, appetite phenylpropan-2-amine) are combined in the licensed
decreases and metabolism improves. Liraglutide has weight-loss medication Qsymia. The initial dose for Qsymia
also been shown to sustain weight loss and concurrently is as follows: 3.75 mg of extended-release topiramate and
provides cardiovascular benefits through the reduction 15 mg of phentermine taken in the morning, once a day. If
of systolic blood pressure and improvement in glycemic required, the dosage can be raised after 14 days (depending
control. 59 on tolerance): 7.5 mg of extended-release topiramate and
Liraglutide is administered once a day and 37.5 mg of phentermine taken in the morning, once a day.
subcutaneously in the thigh, upper arm, or abdomen. It is If the drug is well tolerated and additional weight loss is

Volume 2 Issue 2 (2025) 9 doi: 10.36922/imo.8316