Lasting weight and diabetes benefits seen with tirzepatide, study shows

Tirzepatide is effective for long-term weight loss and diabetes prevention in people with obesity and prediabetes, a trial reported at a meeting of the Obesity Society has demonstrated. 

A new study has found that tirzepatide is associated with a 22.9 per cent weight reduction and a 94 per cent reduction in risk of progression from prediabetes to diabetes over three years.

Dr Louis J. Aronne said: “Here in the US, according to the CDC, approximately 40 million Americans live with diabetes.”

A total of 1,032 adults took part in the SURMOUNT-1 3-year trial, all of whom were diagnosed with prediabetes upon trial enrolment.

The trial consisted of a 20-week dose-escalation period. Participants with prediabetes who remained on tirzepatide during the first 72 weeks underwent a further 104-week treatment period on tirzepatide 5 mg, 10 mg or 15 mg for a total treatment period of 176 weeks, after which participants were followed up 17 more weeks off-treatment to assess safety for the totality of trial duration, according to the presentation.

Key endpoints included mean percentage change in body weight from randomisation to week 176 and time to type 2 diabetes onset at week 176 — during treatment period — and week 193 — during posttreatment follow-up.

Among the original SURMOUNT-1 cohort of 2,539 participants, 40.6 per cent had prediabetes at randomization and were eligible to continue into the SURMOUNT-1 3-year trial.

During 3 years of follow-up, 12.6 per cent of participants assigned to placebo developed type 2 diabetes compared with 1.2 per cent of participants assigned to tirzepatide, which correlated to an HR for diabetes of 0.06 (P < .001), or a 94 per cent reduction in risk for developing diabetes among those with prediabetes taking tirzepatide.

The reported number of SURMOUNT-1 participants needed to treat to prevent one new case of diabetes was nine, according to the presentation. 

During the on-drug treatment period, up to 94.5 per cent of participants assigned to tirzepatide had reversion to normoglycemia compared with 60.4 per cent of those assigned to placebo and lifestyle intervention. 

Approximately 55.2 per cent of diabetes risk reduction was mediated by the weight-loss effects of tirzepatide.

In addition, participants assigned to tirzepatide 15 mg long term also experienced: 

• An average decrease in HbA1c of 0.5 per cent to 0.65 per cent

• A mean reduction in baseline waist circumference from 45.9 inches to 38 inches

• An average 8 mm Hg decrease in systolic BP and a 5.9 mm Hg decrease in diastolic BP

• A more than 14 per cent increase in HDL

• A more than 32 per cent decrease in triglycerides

• Improvement in all lipid levels

• Improvement in all eight domains of the Short Form-36v2 quality of life questionnaire.

Upon treatment discontinuation after 176 weeks on tirzepatide, the researchers reported reversals toward baseline in weight, type 2 diabetes risk and blood pressure during the ensuing 17-week off-drug period.

Dr Ania M. Jastreboff, Director of the Yale Obesity Research Center and Co-Director of the Yale Center for Weight Management, said: “Treatment with all three doses of tirzepatide demonstrated statistically significant and sustained body weight reduction compared with placebo over more than three years.

“Diabetes prevention with tirzepatide over three years resulted in a 94 per cent reduction in progression to diabetes, and nearly 95 per cent reverted from prediabetes to normoglycemia.

“There was improvement in all cardiometabolic measures. Improvements in all domains of health-related quality of life.

“Off-drug weight regain was observed and was accompanied by worsening glycemia and increase in progression to type 2 diabetes.”

Carel Le Roux, Director of the metabolic medicine group at the University College Dublin, summarised: “In people with obesity with prediabetes treatment of the disease of obesity, treatment could achieve control of the disease, but not cure.

“Metabolic complications of obesity got better and stayed better. Functional complications of obesity got better and stayed better.”

Carel Le Roux added: “Mental complications of obesity got better but may return close to baseline. Uncertainty remains regarding what happened with appetitive behaviour.

“We can now shift the focus away from weight loss to health gain. When treating people with prediabetes and obesity we can realise substantial health and functional goals.”