A weekly dose of a diabetes drug appears to lead to significant weight loss in people with obesity, with a recent study showing participants losing as much as 20% of their body weight in a 72-week trial.
Attempts to tackle the disease have long been focused on diet and exercise, but people who shed kilos this way find they often regain it. Now researchers say a diabetes drug, used alongside such interventions, can help people with obesity, The Guardian reports.
Writing in the New England Journal of Medicine, an international team reports that they randomly split 2,539 overweight or obese participants into four equal groups.
One group was given a self-administered weekly placebo injection for 72 weeks, while the other three groups were offered either 5mg, 10mg or 15mg of a drug called tirzepatide. All participants also had regular lifestyle counselling sessions to help them stick to low-calorie meals and at least 150 minutes of weekly physical activity.
On average, participants had a body weight of 104.8kg, with 94.5% deemed obese. Most were white and female, none had diabetes.
The results from those who stuck to the assigned intervention – almost 82% of the sample – reveal that after the 72-week period participants given 5mg of tirzepatide each week lost an average of 16.1kg, those given 10mg lost an average of 22.2kg and those given the 15mg an average of 23.6kg. Those given a placebo injection lost an average of 2.4kg.
Among those assigned the highest dose of tirzepatide, 91% lost 5% or more of their body weight, compared with 35% of those assigned the placebo: 57% of those assigned the highest dose lost 20% or more of their body weight compared with 3% of those assigned the placebo.
“We should treat obesity as we treat any chronic disease – with effective and safe approaches which target underlying disease mechanisms – and these results underscore that tirzepatide may be doing just that,” said Dr Ania Jastreboff of Yale University, the lead author of the research.
The study comes after the UK’s National Institute for Health and Care Excellence (Nice) approved the use of another drug, semaglutide, for certain groups of people with obesity in February.
Prof Rachel Batterham, an obesity expert at University College London who was not involved in the work, said that like semaglutide, tirzepatide worked by mimicking hormones in the body that help people feel full after eating and which are often at low levels in people with obesity.
While semaglutide mimics just one hormone, however, tirzepatide mimics two, potentially explaining why the latter appears to have a greater effect.
“Weight loss is about improving a person’s health. If you want to improve the really difficult complications of obesity, then you need 15-20% weight loss. If you want to improve somebody’s heart failure or get rid of their obstructive sleep apnoea, reduce their risk of dying from cardiovascular disease, then we need much greater weight loss that we can achieve and sustain with diet alone,” Batterham said.
Regarding semaglutide, the NHS greenlighted the weight-loss after a watchdog approved its use.Patients on the weekly injections saw their weight fall by an average of 12% after one year, Nice said.
It has issued draft guidance recommending semaglutide, also known as Wegovy, for adults with at least one weight-related condition, such as obstructive sleep apnoea or heart disease, and a body mass index (BMI) of at least 35. In exceptional cases, some people with a BMI of 30 or more may also be able to access the drug, which is self-administered using a pen injector.
Study details
Tirzepatide Once Weekly for the Treatment of Obesity
Ania Jastreboff, Louis Aronne, Nadia Ahmad, Sean Wharton, Lisa Connery, Breno Alves, Arihiro Kiyosue, Shuyu Zhang, Bing Liu, Mathijs Bunck, and Adam Stefanski for the SURMOUNT-1 Investigators*
Abstract
Background
Obesity is a chronic disease that results in substantial global morbidity and mortality. The efficacy and safety of tirzepatide, a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, in people with obesity are not known.
Methods
In this phase 3 double-blind, randomised, controlled trial, we assigned 2539 adults with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or more, or 27 or more and at least one weight-related complication, excluding diabetes, in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period. Coprimary end points were the percentage change in weight from baseline and a weight reduction of 5% or more. The treatment-regimen estimand assessed effects regardless of treatment discontinuation in the intention-to-treat population.
Results
At baseline, the mean body weight was 104.8 kg, the mean BMI was 38.0, and 94.5% of participants had a BMI of 30 or higher. The mean percentage change in weight at week 72 was −15.0% (95% confidence interval [CI], −15.9 to −14.2) with 5-mg weekly doses of tirzepatide, −19.5% (95% CI, −20.4 to −18.5) with 10-mg doses, and −20.9% (95% CI, −21.8 to −19.9) with 15-mg doses and −3.1% (95% CI, −4.3 to −1.9) with placebo (P<0.001 for all comparisons with placebo). The percentage of participants who had weight reduction of 5% or more was 85% (95% CI, 82 to 89), 89% (95% CI, 86 to 92), and 91% (95% CI, 88 to 94) with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and 35% (95% CI, 30 to 39) with placebo; 50% (95% CI, 46 to 54) and 57% (95% CI, 53 to 61) of participants in the 10-mg and 15-mg groups had a reduction in body weight of 20% or more, as compared with 3% (95% CI, 1 to 5) in the placebo group (P<0.001 for all comparisons with placebo). Improvements in all prespecified cardiometabolic measures were observed with tirzepatide. The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively.
Conclusions
In this 72-week trial in participants with obesity, 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight. (Supported by Eli Lilly; SURMOUNT-1 ClinicalTrials.
NEJM article – Tirzepatide Once Weekly for the Treatment of Obesity (Open access)
The Guardian article – Gamechanging’ weight loss drug to be made available on NHS (Open access)
See more from MedicalBrief archives:
Obesity contributes to up to half of new diabetes cases annually in the US
Obesity increases type 2 diabetes risk six-fold, regardless of genetics
Soaring UK obesity rate boosts paediatric diabetes by 41%