Pharmacologic Obesity Treatment – Emphasis on Efficacy and Cardiometabolic Markers
Pp. 1-19 (19)
Fariha Salman, Ivan Gerling and Helmut O. Steinberg
After a thirteen-year hiatus, the FDA approved two new anti-obesity drugs
in 2012, lorcaserin (brand-name Belviq®) and a fixed-combination of topiramide and
phentermine (brand-name Qsymia®); one new anti-obesity drug was approved in 2014,
a fixed-combination of naltrexone and bupropion (brand-name Contrave®), and in 2015
the “high dose” liraglutide (brand-name Saxenda®) was approved for weight loss.
During this time, the marketed anti-obesity drug sibutramine was withdrawn due to
increase in non-fatal myocardial infarction and stroke incidence , two drugs
targeting cannabinoid receptors were not approvable in the United States and the
European Union due to concerns regarding suicidality and leptin at pharmacologic
doses was not marketed due to disappointing efficacy. All approved drugs, in
conjunction with diet and exercise, achieve more weight gain as compared to placebo.
Efficacy between different drugs cannot be directly compared since no head-to-head
studies have been performed; however, some drugs/drug combinations appear to
provide substantially bigger reductions in weight than others or the respective
monotherapies. Cardiovascular parameters, especially systolic blood pressure,
triglycerides and HDL-cholesterol respond positively to even small amounts of weight
loss; the same holds true for insulin and insulin resistance. Uric acid, an emerging risk
factor for type 2 diabetes and cardiovascular disease, also tends to improve in response
to weight loss although there is an increased short-term risk of gout. All drugs have
specific side effects and several drugs do have black-box warnings; for example, for
female patients, pregnancy needs to be ruled-out before starting topiramate and a
negative pregnancy test is required every 4 weeks while on treatment with Qsymia, and
buproprion needs to be tapered off slowly and not discontinued abruptly to decrease the
risk of seizures. Treating overweight/obese subjects presents an opportunity and a
challenge to physicians and patients. To achieve optimal weight loss with least
complications, patients need to work on hypocaloric diets and exercise and physicians need to know the prescribing information of the prescribed weight-loss
Blood Pressure, Combination-Therapy, Glucose, Lipids, Mono-
Therapy, Weight Loss.
Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Tennessee Health Science Center, Memphis, TN, USA.