US Population Eligibility and Estimated Impact of Tirzepatide Treatment on Obesity Prevalence and Cardiovascular Disease Events

“Moreover, the importance of obesity as a risk factor for cardiovascular disease (CVD) is well-established [4, 5], warranting the need to further demonstrating the value of weight loss interventions on reducing CVD outcomes.”

“It is well-established that certain glucagon like peptide-1 (GLP-1) receptor agonists reduce CVD events in persons with diabetes [6, 7].”

“…given that weight reduction was the primary endpoint in the SURMOUNT-1 trial, a sensitivity analysis was done using the laboratory-based equations [13] (Appendix) and the respective SURMOUNT-1 trial effects on total and high-density lipoprotein-cholesterol (HDL-C) (of − 7.4% and + 8.2%,…”

“It is well-established that certain glucagon like peptide-1 (GLP-1) receptor agonists reduce CVD events in persons with diabetes [6, 7].”

“Most recently, oral GLP1-RA therapies, such as semaglutide 50 mg in the OASIS 1 trial, showed significant weight reductions averaging 15.1% [19], similar to that achieved in the earlier STEP 1 trial [9] with injectable semaglutide.”

“Moreover, the importance of obesity as a risk factor for cardiovascular disease (CVD) is well-established [4, 5], warranting the need to further demonstrating the value of weight loss interventions on reducing CVD outcomes.”

“We then applied the risk factor changes from the SURMOUNT-1 trial tirzepatide 15 mg group (as shown in Table S4 in the Appendix of the SURMOUNT-1 publication [11]) to estimate the “post-treatment” 10-year CVD risk similarly with these equations.”

“Recently reported and ongoing cardiovascular outcomes therapies of newer obesity therapies [11, 22] will document true efficacy of these agents in improving CVD outcomes in persons who are overweight or with obesity.”

“By the end of this decade, half of US adults are expected to have obesity and nearly a fourth will have severe obesity [3].”

“Keywords Obesity · Cardiovascular disease · Prevention · Tirzepatide · Glucagon-like peptide-1 (GLP-1) · Glucose-dependent insulinotropic peptide (GIP) More than 40% of the US adult population has obesity, and nearly three-fourths are either overweight or obese [1].”

“Finally, early studies of the oral non-peptide GLP-1 receptor agonist orforglipron [20], as well as newer triple hormone agonists such as retatrutide [21], are showing benefits of significant weight loss efficacy.”

“Most recently, oral GLP1-RA therapies, such as semaglutide 50 mg in the OASIS 1 trial, showed significant weight reductions averaging 15.1% [19], similar to that achieved in the earlier STEP 1 trial [9] with injectable semaglutide.”

“It has been previously reported that GLP1-RA therapy reduces weight more in those without diabetes (but with overweight or obesity) than among those with diabetes [17].”

“Recently, however, GLP-1 receptor agonists liraglutide [8] and semaglutide [9] in dosages greater than those used for diabetes provide substantial body weight loss and have generated significant excitement in these and other weight loss therapeutics.”

“Moreover, in a recent analysis of NHANES [27], 51.1% of US adults were estimated to meet the FDA eligibility criteria for tirzepatide with Black (56.6”

“…signaling together with the effects of glucagon increasing energy expenditure leading to potentially greater weight loss than GLP-1 agonism alone [10], The SURMOUNT-1 trial recently demonstrated the efficacy of once weekly tirzepatide in adults who are overweight or with obesity to result in up…”

“…semaglutide 2.4 mg, identifying 93 million US adults with overweight or obesity to be eligible based on STEP 1 trial eligibility criteria, with up to a 1.8% absolute (17.8% relative) CVD risk reduction projected that translates to an estimated 1.5 million pre-ventable CVD events over 10 years [28].”

“Having this information may be helpful to better understand the potential CVD benefits of tirzepa-tide as well as the implications of the ongoing tirzepatide SURMOUNT-MMO cardiovascular outcomes trial [12].”

“…and potential preventable events among US NHANES adults with diabetes, estimating 15.4% (4.2 million) of those with diabetes to fit LEADER eligibility criteria and from LEADER trial CVD outcome risk reductions observed, 21,209 primary composite CVD events could be prevented annually [26].”

“9,11 The results are consistent between these current analyses of SURMOUNT-5 data and those by Wong et al. 13,14 particularly in the treatment effect of tirzepatide vs. semaglutide on CVD risk reduction.”

“[11] Factors such as physical activity, [12] stress, depression, lifestyle modifications, and alcohol consumption, [13 – 15] each of which can contribute to the progression of SLD, may have also been altered by the COVID-19 pandemic.”

“14 There are strengths and limitations to our study.”