Pharmacological Approach for Obesity
Pp. 67-81 (15)
Mohannad Kusti, Forrest Olgers and Ehab Akkary
Obesity has reached epidemic levels in the US and represents a major health and
economic challenge. The weight loss process generally starts with behavioral modification and ends
with surgical intervention in cases of severe or morbid obesity. Pharmacological therapies present a
valid option for patients who are overweight or morbidly obese as an in addition to the role of
behavioral modification, diet and exercise. This option should also be considered for post-operative
patients with inadequate weight loss who are not candidates for revisional bariatric procedures.
Weight loss medications (WLMs) can be divided into the following categories:
1. Noradrenergic Appetite Suppressants (NASs): more commonly used. Examples include
phentermine, sibutramine, phendimetrazine, and diethylpropion.
2. Pancreatic Lipase Inhibitors (PLIs): examples include orlistat.
3. Fat Substitutes (FSs): examples include olestra which has been integrated into snack
foods but not been studied as a formal weight loss medication.
4. Cannabinoid Receptor Antagonists (CRAs): examples include Rimonabant.
5. Thermogenics and Stimulators of Fat Mobilization.
There is multiple OTC and commercial brands, it is important to differentiate between the different
types and their mechanism of action, for example Alli is the OTC version of orlistat with same
mechanism and side effects.
Since the obesity “disease” is chronic, the medications have to be weighed carefully in terms of the
risks and benefits for long term use.
Sibutramine, as a commonly used NAS, is a centrally acting serotonin/ noradrenaline reuptake
inhibitor and increases thermogenesis. Studies showed weight reduction of 4.45 kg for sibutramine
compared to placebo with overall improvement in the metabolic profile e.g. decreased triglycerides,
increased HDL, and improved Hgb A1C. The main side effect is tachycardia; there is conflicting
studies about the effect on blood pressure so overall NASs are not recommended in patients with
uncontrolled hypertension, or in case of history of cardio- and cerebrovascular disease.
Orlistat, a PLI, blocks the lipolysis of dietary triglycerides. A recent meta-analysis showed mean
weight loss of 2.89 kg with overall improvement of the metabolic profile especially diabetes
parameters; however there was no effect on HDL and triglycerides. As mentioned, the side effects
are mainly gastrointestinal but can cause considerable inconvenience for patients for example
greasy diarrhea, incontinence, urgency and oily spotting. Overall it is not recommended for patients
with malabsorption or cholestasis.
Rimonabant, as a CRA, inhibits the overactivation of the endocannabinoid system resulting in
central anorexia. Rimonabant seems to have effects on the metabolism through the adipose tissue,
liver, skeletal muscles and the pancreas. There are four published RIO trials (Rio-North America,
RIO-Europe, RIO-Lipids, RIO-Diabetes), rimonabant decreased weight by 6.3-6.9 kg in the nondiabetic
groups vs. placebo (-1.5-1.8 kg) (p <0.001), whereas in the diabetic subjects enrolled in
RIO-Diabetes, weight loss was 5.3 vs. 1.4 kg in the placebo group with overall improvement in the
metabolic profile in diabetic and non-diabetic patients. Rimonabant is contraindicated in patients
with history of depression, suicidal ideation or uncontrolled psychiatric disorder.
In spite of the fact that serotonergic agents (fenfluramine, dexfenfluramine) were withdrawn from
the US market in the late 1990’s secondary to their cardiovascular and pulmonary complications. At
the present time, it is very important to assess the patient’s history regarding their intake as this
might result in further cardiac or pulmonary evaluations.
In conclusion, WLMs have shown decrease in body weight and improved metabolic and
cardiovascular risk factors. Since, the weight loss is modest, they should be considered in
overweight (BMI 25 – 29.9kg/m2) or obese (BMI 30 – 34.9 kg/m2) patients and should not be
considered as an alternative for surgical intervention in patients with higher BMIs. Diet, exercise
and behavioral modification should always be implemented regardless of the weight loss means
Obesity, medical weight loss, appetite suppressants, lipase inhibitors, fat substitutes,
Department of Bariatric and Advanced Laparoscopic Surgery, Preston Memorial Hospital, Kingwood, West Virginia, USA.