Cardiovascular Risk Reduction Associated with Pharmacological Weight Loss: A Meta-Analysis.

Background: Obesity is a growing pandemic that is associated with multiple cardiovascular disease (CVD) risk factors such as hypertension, diabetes, dyslipidemia and obstructive sleep apnea. With the increase in obesity rates where nearly two thirds of Americans are either obese or overweight, there has been an increase in the use of pharmacological therapy weight loss. While these therapies have shown benefit in weight reduction, the clinical impact these pharmacological agents on overall CVD outcomes has yet to be determined.

Aim: We aimed to assess the effect of pharmacological agents used for weight reduction on CVD risk and all-cause mortality.

Methods: We conducted a meta-analysis of peer-reviewed literature that evaluated the impact of anti-obesity drugs on cardiovascular outcomes. Key words used included: "orlistat", "lorcaserin", "phentermine/topiramate" or "naltrexone/bupropion" and "cardiovascular outcomes" among others. We reviewed 791 articles, only 47 studies were randomized controlled trials and only 7 studies fulfilled all the inclusion criteria including, quantitative data on cardiovascular risk factors such as, Hemoglobin A1C (A1C), changes in body mass index (BMI), blood pressure and CVD morbidity and mortality. Data was retrieved from these studies and evaluated with comprehensive meta-analysis software^® to assess pooled effects for medical management versus placebo.

Results: There were 7 studies included in the final analysis, with a total of 18,598 subjects, of which 8,685 were in the intervention (INT) group and 9,913 in the control (CTRL) group. For all cause mortality, there were 45 events in the INT and 55 in the CTRL groups, suggesting no significant difference between the two groups (OR: 0.843, 95%CI: 0.571-1.244, Z: -0.860, P: 0.390). For CVD mortality, there were 17 events in the INT and 36 events in the CTRL groups suggesting a significant mortality benefit in the INT group (OR:0.496, 95% CI: 0.282-0.873, Z: -2.433, P: 0.015). There was a significant absolute reduction in A1C in the INT group (Hg: -0.238, 95%CI: -0.291 to -0.186, Z: -8.937, P< 0.001). The percentage weight reduction was significantly higher for the INT group compared to the CTRL group (Hg: -0.431, 95%CI: -0.477 to -0.385, Z: -18.472, P< 0.001) and the blood pressure reduction was higher for the INT group compared to the CTRL group. (Hg: -0.052, 95%CI: -0.101- -0.003, Z: -2.086, P: 0.037). The heterogeneity observed for our meta analysis is Q: 1.884, df: 6, P: 0.930.

Conclusions: Our study demonstrated the favorable and significant effect of pharmacological weight reduction strategies on weight loss, blood pressure reduction, glycemic control (A1C reduction), and CVD mortality.While weight loss without pharmacological means has been shown to reduce CVD risk, the mechanism by which weight loss medications impact CVD risk reduction could be a direct effect of these agents or merely an effect of weight reduction itself. Weight loss has been noted to modify risk factors via improving insulin sensitivity, reducing inflammation, decreasing blood pressure and modifying the lipid profile, In addition, the mechanism of action of the medications are not directly anti-inflammatory, and do not directly modify insulin sensitivity, blood pressure or the lipid profile. Thus, it is most likely that the benefit on cardiovascular disease from these therapies is via weight reduction and not direct medication effect.Given the limited efficacy of the lifestyle modification on sustained weight loss and the surgical risk and limited availability of bariatric surgical options. Our data suggests pharmacological weight loss therapy may be a valuable treatment option to reduce CVD risk in obese patients. Further research is needed to clarify the effects these therapies on overall mortality and evaluate the mechanisms by which these medications reduce CVD risk factors and mortality.