New Triple-Hormone Injection Shows Major Weight Loss in People with Type 2 Diabetes and Obesity

Key Takeaways:

• In a phase 3 trial, retatrutide cut body weight more than four times as much as placebo and roughly doubled the reduction in long-term blood sugar.
  
• The once-weekly jab works through three hormone pathways at once – GLP-1, GIP and glucagon – the last of which may help raise energy expenditure.
  
• Experts called the results encouraging but stressed that head-to-head trials against existing drugs are still needed.
  
  
  

A new approach to managing type 2 diabetes

A once-weekly injection that works through three hormone pathways at the same time could deliver substantial reductions in both blood sugar and body weight for people with type 2 diabetes, according to phase 3 trial results.

People taking part in the trial who received weekly retatrutide injections over 40 weeks lost more than four times as much weight as those given a placebo, while their average reduction in long-term blood sugar (HbA1c) was more than twice that seen in the placebo group.

How retatrutide works

Retatrutide is described as a triple-hormone drug because it mimics three gut hormones that help regulate appetite, blood sugar and metabolism: GLP-1, GIP and glucagon.

This sets it apart from several medications already in use. Drugs such as Ozempic and Wegovy primarily target the GLP-1 pathway to suppress appetite, while Mounjaro combines GLP-1 with GIP to help control blood-sugar levels. Retatrutide goes a step further by also engaging the glucagon receptor, which is thought to help increase energy expenditure.

Inside the phase 3 trial

The trial, published in the Lancet, randomly assigned 930 adults with type 2 diabetes to receive either 4mg, 9mg or 12mg of retatrutide, or a placebo.

None of the participants were already taking diabetes medicines. All had inadequately controlled blood-sugar levels and a body mass index (BMI) of at least 23.

Throughout the trial, researchers monitored a range of health markers, including HbA1c, weight, cholesterol levels and other indicators, and recorded any side-effects that arose.

What the results showed

After 40 weeks, participants receiving retatrutide saw their HbA1c fall by an average of about 1.7–1.9 percentage points, compared with 0.8 in the placebo group.

The weight loss results were similarly marked. On average, participants taking retatrutide lost about 11.5%–15.3% of their body weight, against 2.6% for those on placebo. Cholesterol and blood pressure also improved among people taking the drug.

Safety and side-effects

Fourteen participants experienced serious adverse events during the trial, including two in the placebo group. For most people, however, side-effects were mild to moderate and eased over time, with gastrointestinal symptoms the most commonly reported.

What the findings could mean

The study authors say this triple-action medication has the potential to improve health outcomes for some people, including greater weight loss, particularly for those who may need more intensive treatment regimens to manage their type 2 diabetes. Further clinical trials are continuing.

The results follow earlier findings from the manufacturer, Eli Lilly, which suggested that retatrutide was highly effective at reducing weight among people with obesity.

What the experts say

Dr Kath McCullough, special adviser on obesity at the Royal College of Physicians, said the findings were very encouraging.

“For many people living with diabetes and obesity, treatments like this could be genuinely life-changing,” she said.

“However, medications are not a silver bullet. While they are proving to be effective, the long-term goal must be to prevent people from needing them in the first place.”

Dr Marie Spreckley, a specialist in prevention of diabetes and related metabolic disorders at IMS Epidemiology, University of Cambridge, said the results were striking: “The magnitude of weight loss observed is particularly notable. However, because this study compared retatrutide with placebo rather than semaglutide or tirzepatide, it is not possible to determine from this data whether retatrutide is superior, equivalent or inferior to currently available therapies. Direct head-to-head trials will be required before firm conclusions can be drawn regarding comparative effectiveness.”

She added that weight loss alone did not necessarily equate to optimal health outcomes, and that people needed support to maintain adequate nutritional intake, preserve muscle mass and maximise long-term health during treatment.

Dr Lucy Chambers, the head of research impact and communications at Diabetes UK, said: “These encouraging findings show that this new class of drug for type 2 diabetes could deliver dual benefits for both weight loss and blood-sugar management. We look forward to further research to understand its long-term effects and how it compares to treatments already available on the NHS.”

Source: The Guardian