EASD 2022: Overcoming Challenges in Obesity Medicine: The SURMOUNT Clinical Development Program
The program focuses on understanding obesity as a neurological disease and its management with Tirzepatide, a novel GIP and GLP1 receptor analogue through the SURMOUNT Clinical Development Program.
Most of the treatments that have come to market for obesity are effectively de-risked by first starting the treatments in people with type two diabetes. Obesity treatments such as pharmacotherapy or surgical therapy produces a heterogeneous response. Tirzepatide is a novel GIP and GLP1 receptor analogue which is built on a GIP background, but it has interaction with the GLP1 receptors and therefore has about a half-life of five days. By using Tirzepatide in type 2 diabetes patients, one third of patients lose more than 15% of their body weight.
The SURMOUNT 1 is a double-blind, randomized, controlled trial, done in 2539 patients to assess efficacy and safety of Tirzepatide 5mg, 10mg and 15 mg once weekly in participants with obesity or without Type 2 diabetes and who have obesity, or overweight with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease with type 2 diabetes. The patients in the trial had a mean BMI of 38 kg/m2and 40% had pre-diabetes. The participants who had pre-diabetes at study commencement will remain enrolled in SURMOUNT-1 for an additional 104 weeks of treatment following the initial 72-week completion date to evaluate the impact on body weight and potential differences in progression to type 2 diabetes at three years of treatment with tirzepatide compared to placebo. The placebo group lost on average 2.4%, whereas the Tirzepatide 15 mg group lost on average 22.5%; in the Tirzepatide 5mg group weight reduction of 16% was achieved. In terms of absolute change in weight in kilograms, the placebo group on average lost 2.4 kilograms, whereas with
Tirzepatide, the average weight reduction was 16-24 kilograms with the 15mg dose.
With respect to a reduction target of greater than or equal to 5%, more than 90% of participants achieved this target and more than 50% achieved the target of greater than or equal to 20% with Tirzepatide; 98% of participants lost weight with the 15 milligram appetite dose, whereas only 2.3% gained weight with Tirzepatide 15mg.
Pooled results with Tirzepatide show that this group lost 33.9% of fat mass versus placebo (8.2%). With respect to visceral fat, mass percent change, placebo group lost 7.3%, whereas the Tirzepatide group lost 40.1%. Tirzepatide had a 3 times greater percent reduction in fat mass than lean mass, resulting in overall improvement in body composition. Tirzepatide patients experienced a significant reduction in fat mass to lean mass ratio with greater reduction seen in patients who lost greater than or equal to 15% of their body weight. HbA1c reduced by 0.5% during the course of the trial; of the 40% of participants with prediabetes more than 95% reverted to normal glycaemia with Tirzepatide; fasting insulin decreased by nearly 47% and there was a reduction in the glucose levels and insulin levels at week 72. There was increase in insulin sensitivity in all the Tirzepitide groups regardless of baseline glycemic status(prediabetes or normoglycemia). Tirzepatide also brought about improvements in the lipid levels as well as blood pressure while increasing HDL- C.
There were similar incidences of serious adverse events in placebo and Tirzepetide groups.There was no increase in incidence of deaths in Tirzepitide group as compared to placebo. The most frequently reported gastrointestinal related adverse events were nausea, diarrhoea, constipation which occurred more in Tirzepitide group as compared to placebo.
Most gastrointestinal events were transient, occuring primarily during the dose-escalation period, and were mostly mild-moderate in severity.
Discontinuation of study drug due to gastrointestinal events which was the primary reason for discontinuation were reported in less than 5% of participants. There were 4 reported cases of adjudication-confirmed pancreatitis, evenly distributed across Tirzepitide and placebo groups. The overall incidence of cholecystitis was low. With respect to quality of life, a short-term survey showed that Tirzepatide improved aspects of social function, physical function, emotional role function and mental health.
In conclusion, the results of the SURMOUNT 1 trial favour Tirzepatide as potential obesity medicine.
S 21, European Association for the Study of Diabetes (EASD) International Congress 2022, 19th – 23rd Sept. 2022, Stockholm
