Weight loss meds confer minimal impact on cardiometabolic risk
The use of weight loss medications for at least 1 year did little to improve cardiometabolic risk factors in obese adults, according to a systematic review and meta-analysis.
“Though FDA-approved pharmacological agents for long-term treatment of obesity result in significant weight loss … they appear to have modest impact on modifying key cardiometabolic risk-factors, even one year after therapy,” said the researchers.
“Most drugs were associated with improvements in waist circumference, but only marginal improvements in serum cholesterol profile and [blood pressure],” they said.
Researchers analysed 28 randomized controlled trials which compared the effects of ≥1 year of treatment with FDA-approved weight loss medications (ie, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide) with placebo or other active agents in obese adults (n=29,018, median age 46 years, median baseline BMI 36.1 kg/m2, 77 percent female).
With regards to effect of medication on cardiometabolic risk factors, a standardized mean difference (SMD) of <0.2 suggested minimal benefit, 0.2–0.4 suggested modest benefit, 0.4–0.7 suggested moderate benefit, and >0.7 suggested a large benefit.
Overall, weight loss medications were associated with modest reductions in fasting blood glucose levels (weighted mean difference [WMD], -4.0 mg/dL, 95 percent confidence interval [CI], -4.4 to -3.6; SMD, -0.27) and waist circumference (WMD, -3.3 cm, 95 percent CI, -3.5 to -3.1; SMD, -0.36) compared with placebo. [Gastroenterology 2018;doi:10.1053/j.gastro.2017.12.024]
Conversely, weight loss medications had little impact on systolic or diastolic blood pressure or cholesterol levels compared with placebo, though the impact differed by medication.
“The effect of individual drugs varied substantially and closely followed their mechanism of action,” the researchers said.
For instance, compared with placebo, the antidiabetic drug liraglutide was associated with a moderate reduction in fasting blood glucose (WMD, -15.6 mg/dL), HbA1c (WMD, -0.5 percent), and waist circumference (-4 cm) but had a minimal effect on blood pressure and cholesterol levels.
Compared with placebo, the lipase inhibitor orlistat was associated with reductions in HbA1c (WMD, -0.4 percent) and LDL- (WMD, -8.7 mg/dL) and HDL-cholesterol levels (WMD, -1.1 mg/dL).
The use of phentermine-topiramate was associated with reductions in waist circumference, fasting blood glucose, HbA1c, and systolic blood pressure levels but had a minimal impact on cholesterol levels, while naltrexone-bupropion was associated with an increase in HDL-cholesterol but just a minimal impact on fasting blood glucose and waist circumference.
None of the medications improved all cardiometabolic risk factors and no medications proved superior to the others.
According to the researchers, these findings contradict those obtained with other weight-loss therapies, notably bariatric surgery which has been associated with improvements in cardiometabolic risk factors in both diabetics and nondiabetics. [JAMA Surg 2014;149:716-726, Obes Surg 2012;22:1723-1729]
“This likely represents a combination of greater magnitude of weight loss with bariatric surgery as compared with pharmacotherapy, and neurohormonal changes secondary to bariatric surgery, such as increases in incretin or satiety hormones, and improvement in biochemical, inflammatory, and oxidative profiles,” they said.
The researchers acknowledged that potential between-study heterogeneity and the use of trials that mostly compared an active weight loss drug against placebo may have impacted the findings. Most studies included in the meta-analysis also did not exceed a 1-year treatment period and studies with longer follow-up periods may better establish long-term cardiovascular risk and benefit of weight loss medications, they said.