PROJECT SUMMARY/ABSTRACT
Over 40% of US adults have obesity, many with weight-related complications such as hypertension and diabetes.
Current clinical guidelines suggest lifestyle change as the first-line obesity treatment approach, but this does not
produce sustained clinically-significant weight loss for the majority of patients. Bariatric surgery is available for
patients with more severe obesity, but due to its cost, invasiveness and risk, only 1-2% of eligible patients
undergo a procedure. Addressing the obesity epidemic using only lifestyle change programs and bariatric
surgery will continue to leave most patients without a successful long-term treatment option. Anti-obesity
medication (AOM) is an option that could help to fill the current obesity treatment gap. Recent trials have
demonstrated that AOMs lead to enduring clinically-significant weight loss, with a good safety profile. However,
many physicians remain hesitant to prescribe AOMs due to concerns about their effectiveness and safety. There
is also a complete lack of comparative effectiveness data on contemporary AOM options. Studies addressing
these issues could inform treatment choices, guidelines, and pharmacy benefit development, significantly
impacting clinical practice. We will use a nationwide commercial insurance claims dataset that includes over
350,000 unique adults with new AOM fills (data current through early-2022) to conduct the first nationwide
comparative effectiveness study of AOMs. We will compare propensity score-matched cohorts of patients
prescribed one of six FDA-approved AOMs between 2012 and 2027: phentermine, phentermine-topiramate-ER,
liraglutide, bupropion-naltrexone-SR, semaglutide, and tirzepatide (pending approval 2023). Our primary design
will use intention-to-treat analyses on new users with at least one AOM fill, but we will also conduct on-treatment
and per-guidelines analyses among patients with persistent AOM use. Our Specific Aims are to compare groups
of patients prescribed these AOMs, over up to 5 years of follow-up, with respect to: (1) Major cardiovascular
events; (2) Other clinical outcomes related to reduction in body weight, including (a) incidence of type 2 diabetes
(T2D), hypertension and dyslipidemia; and (b) Change in intensity of T2D, hypertension and dyslipidemia
pharmacotherapies (including discontinuation of therapy); and (3) Health care services use and associated costs,
including annual hospital days; emergency department visits; outpatient visits; and pharmacy, lab, and medical
costs. In an exploratory Aim, we will examine whether key patient characteristics (age, sex, baseline T2D,
comorbidity burden) modify the risks or benefits seen with each AOM. Comparative effectiveness studies
examining major clinical and health services outcomes beyond weight loss are needed to inform guidelines and
policy. Our use of a large, existing, regularly updated dataset will allow us to efficiently produce rapid-turnaround
real-world results that are highly generalizable and likely to have a significant impact on treatment of a chronic
disease that affects nearly half of American adults.
