A new once-weekly injection for type 2 diabetes has delivered “striking” reductions in blood sugar and body weight in a large phase 3 trial, with patients on the highest dose losing more than a third of their weight by the end of the study.
The trial, published in The Lancet, involved 930 adults with type 2 diabetes and inadequately controlled blood sugar levels. All had a body mass index of at least 23 and were not already taking diabetes medicines. Participants were randomly assigned to receive weekly injections of retatrutide at doses of 4mg, 9mg or 12mg, or a placebo, for 40 weeks.
After the treatment period, the average drop in long-term blood sugar – measured by HbA1c – was about 1.7 to 1.9 percentage points in those receiving retatrutide, more than double the 0.8 percentage point fall seen in the placebo group. Up to 90% of participants on the drug achieved an HbA1c below 7.0%, and up to 46% reached a level below 5.7%, which is the threshold for normal blood sugar.
Weight loss was also substantial. Participants on retatrutide lost an average of 11.5% to 15.3% of their body weight, compared with just 2.6% on placebo. For the 12mg dose, the average weight loss was 36.6 lbs (16.8%) at 40 weeks, with weight loss still ongoing when the trial ended. Overall, patients in the drug group lost more than four times as much weight as those on placebo.
Additional health markers improved too. Cholesterol levels fell, blood pressure dropped, and the drug produced significant reductions in triglycerides (up to 41%), non-HDL cholesterol (up to 24.2%), systolic blood pressure (up to 12.3 mmHg) and waist circumference (up to 9.5 inches), according to the trial data.
How retatrutide differs from existing diabetes drugs
Retatrutide, developed by Eli Lilly, belongs to a new class of medication known as a triple agonist. It mimics three gut hormones that regulate appetite, blood sugar and metabolism: GLP‑1 (glucagon-like peptide‑1), GIP (glucose-dependent insulinotropic polypeptide) and glucagon. This triple action is designed to control the body’s metabolic processes more comprehensively than existing treatments.
GLP‑1 slows digestion, suppresses appetite and stimulates insulin production. GIP also increases insulin release and reduces food intake. The key addition is glucagon: activating the glucagon receptor is believed to boost energy expenditure and promote fat metabolism, including direct mobilisation of liver fat.
This multi-receptor approach sets retatrutide apart from other injectable diabetes drugs. Ozempic and Wegovy (both semaglutide) target only the GLP‑1 pathway, primarily to suppress appetite. Mounjaro (tirzepatide) combines GLP‑1 and GIP to control blood sugar and weight but does not engage the glucagon receptor. Retatrutide is the first in its class to bind all three receptors, offering what researchers describe as a broader metabolic scope.
While direct head-to-head trials comparing retatrutide with semaglutide or tirzepatide are not yet available, separate data from Eli Lilly’s obesity programme suggest the triple agonist may produce greater weight loss. In the TRIUMPH‑1 trial, which included 2,339 adults with obesity or overweight but without diabetes, those on the 12mg dose lost an average of 70.3 lbs (28.3% of body weight) after 80 weeks. For participants with a baseline BMI of 35 or above who continued treatment, average weight loss reached 85.0 lbs (30.3%) at 104 weeks, with no sign of plateauing. By comparison, semaglutide typically produces weight loss of around 15–17% and tirzepatide around 20–22% in separate trials. Some analysts have described retatrutide as the “highest-efficacy pharmacological weight loss agent to date in a large pivotal trial”.
The obesity studies also showed improvements in conditions related to excess weight. Knee osteoarthritis pain was reduced by up to 73.1%, and the severity of obstructive sleep apnea was cut by up to 60.6%. Changes in circulating metabolites and lipids suggested improved metabolic health and a lower cardiovascular risk profile.
Safety and side effects
The most common side effects of retatrutide were gastrointestinal – nausea, diarrhoea, vomiting and constipation – which were dose-dependent and tended to ease as the body adjusted. Nausea affected up to 60% of participants at the highest doses in earlier phase 2 trials. Other reported side effects included dysesthesia, an unusual tingling or altered skin sensation that occurred in up to 20.9% of those on the 12mg dose in phase 3, possibly linked to glucagon receptor activity; a small increase in heart rate of about 5–10 beats per minute that peaked around week 24 and then declined; and mild injection-site reactions.
During the diabetes trial, 14 participants experienced serious adverse events, including two in the placebo group. The authors noted that for most patients side effects were mild to moderate and resolved over time. Rare but serious risks requiring immediate medical attention include pancreatitis and gallbladder problems such as gallstones.
Expert reaction
Dr Kath McCullough, special adviser on obesity at the Royal College of Physicians, called the findings “very encouraging” and said that for many people living with diabetes and obesity, treatments like this “could be genuinely life-changing”. However, she warned that “medications are not a silver bullet” and that the long-term goal must be prevention. Dr McCullough is a consultant in bariatric medicine, diabetes and endocrinology.
Dr Marie Spreckley, a specialist in diabetes prevention and related metabolic disorders at the IMS Epidemiology unit at the University of Cambridge, described the results as “striking”, particularly the magnitude of weight loss. But she pointed out that because the trial compared retatrutide with a placebo rather than with semaglutide or tirzepatide, “it is not possible to determine from this data whether retatrutide is superior, equivalent or inferior to currently available therapies”. She added that “direct head-to-head trials will be required before firm conclusions can be drawn regarding comparative effectiveness”. Dr Spreckley also stressed that weight loss alone does not necessarily equate to optimal health outcomes and that patients need support to maintain adequate nutritional intake, preserve muscle mass and maximise long-term health.
Dr Lucy Chambers, 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.”
Regulatory status and availability
Retatrutide is not yet approved in the UK. It remains an investigational drug, and regulatory submissions to the Medicines and Healthcare products Regulatory Agency (MHRA) are expected in late 2026 or early 2027, with potential marketing authorisation from late 2027 to mid-2028. If approved, NHS availability would require a separate NICE technology appraisal, which typically takes an additional 12–18 months, meaning the drug could reach NHS patients from 2029 at the earliest. Private prescribing could follow MHRA approval within weeks, as has been seen with tirzepatide and semaglutide.
Eli Lilly is continuing to run phase 3 trials under the TRIUMPH programme, evaluating retatrutide for obesity, type 2 diabetes, knee osteoarthritis, obstructive sleep apnea, cardiovascular and renal outcomes, and metabolic dysfunction-associated steatotic liver disease. The authors of the diabetes trial said the drug has the potential to improve health outcomes for some patients, especially those who may require more intensive treatment regimens. Members of the public are strongly advised against purchasing products labelled as “retatrutide” online, as these are unregulated, untested and potentially dangerous research chemicals.