by Ildiko Lingvay, MD, MPH, MSCS

SURMOUNTING-ing the War on Obesity

Obesity has become an epidemic over the past three decades,¹ and ongoing and mounting environmental and social pressures are driving the future forecasts to unconceivable and seemingly unsurmountable levels. According to projections based on data collected from the Behavioral Risk Factor Surveillance System (BRFSS) from 1990 to 2016, by 2030 approximately half of the US population will meet criteria for obesity – and over a quarter of the population will meet criteria for severe obesity.² Considering the wide-ranging morbidity and mortality associated with obesity,³ these numbers are beyond alarming and an urgent call to action for society.

Obesity is a disturbance in the body’s energy homeostasis, resulting from an imbalance between energy availability and energy expenditure layered on a predisposing genetic background. However, unlike many other homeostatic mechanisms in humans, energy homeostasis is uniquely vulnerable to extrinsic pressures. Modern society has applied unprecedented pressures on the system, leading to a public health crisis with no simple solution. Tackling such a complex problem requires multifaceted approaches. Prevention remains the most desirable strategy at a societal level, but effective treatment solutions are needed to improve the health of the individuals affected by this disease.

Tirzepatide promises to become the “sharpest” tool in our non-surgical armamentarium to fight the war on obesity. At this year’s American Diabetes Association annual scientific meeting the results of the first large-scale randomized clinical trial evaluating the efficacy and safety of tirzepatide in persons with obesity (and without diabetes) were revealed, and concurrently published in the New England Journal of Medicine.⁴ In the SURMOUNT 1 study, over a 72-week treatment period, those treated with 15 mg of tirzepatide lost on average 22% of their body weight – an efficacy level approaching that of bariatric surgery. Importantly, most people treated lost weight, in fact over 96% of patients lost at least 5% of their body weight, and an impressive 40% lost at least 25% of their initial body weight. As expected, such improvements in body weight were associated with improvements in all measured cardiovascular risk factors, including blood pressure, total cholesterol and its components, triglycerides and free fatty acids, glucose levels, insulin levels, as well as quality of life. Furthermore, 95% of those who had pre-diabetes at baseline (approximately 40% of the baseline population) reverted to a normoglycemic state.

The overall tolerability of tirzepatide was very good, with 7% or fewer participants treated with tirzepatide discontinuing study drug due to adverse events (2.6% equivalent rate in placebo); there were no safety related surprises, and the type and rate of side effects were as expected for the incretin class of medications. Nausea was reported by up to one-third of the participants treated with tirzepatide, diarrhea by up to 23%, constipation by up to 17.1%, and vomiting by up to 12.2%.

These results surmount those of all prior non-surgical interventions studied so far and compare quite well – especially when the entire efficacy and long-term safety are considered – with those of bariatric surgery. While still finding ourselves standing very far from capturing the victory flag on obesity, today we celebrate the promise of a “sharp” tool in our armamentarium to surmount the war on obesity.

 

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References

1. Adult Obesity Facts. https://www.cdc.gov/obesity/data/adult.html.
2. Ward ZJ, Bleich SN, Cradock AL, et al. Projected U.S. State-Level Prevalence of Adult Obesity and Severe Obesity. N Engl J Med 2019;381(25):2440–50.
3. Abdelaal M, le Roux CW, Docherty NG. Morbidity and mortality associated with obesity. Ann Transl Med 2017;5(7):161.
4. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Once Weekly for the Treatment of Obesity. N Engl J Med 2022; doi: 10.1056/NEJMoa2206038.