Increasing semaglutide dose showed very unexpected weight loss results in trials

A higher weekly dose of semaglutide helped adults with obesity lose about 19 percent of their body weight, and it did so over a long, carefully monitored period that followed strict protocols and consistent follow up visits.

Researchers ran parallel trials in people with and without type 2 diabetes at sites across multiple countries, comparing the higher dose with the current standard dose and with placebo to understand its full impact.

Testing higher semaglutide dose

Semaglutide belongs to a class called GLP-1 receptor agonist, medicines that mimic a natural gut hormone to reduce appetite and improve blood sugar control. Doctors already use a 2.4 mg weekly dose for chronic weight management in adults.

The work was led by Sean Wharton, MD, at the University of Toronto (UT). His research focuses on clinical weight management and obesity care.

In obesity care, some people do not reach their goals on the currently approved dose. A large phase 3b study  tested a higher weekly dose in adults without diabetes to see whether more weight loss and better metabolic changes would follow.

A parallel trial enrolled adults with obesity and type 2 diabetes to answer the same question in a group that often faces tougher weight loss and blood sugar targets.

What the trials found

The adult trial without diabetes reported a weight change of 18.7 percent with 7.2 mg, 15.6 percent with 2.4 mg, and 3.9 percent with placebo, across 72 weeks. Participants on the higher dose were also more likely to reach large losses of 20 percent and 25 percent.

Reductions extended beyond the scale. Waist circumference fell by 11.7 centimeters, about 4.6 inches, which tracks with less abdominal fat and lower risk for complications.

In adults with obesity and type 2 diabetes, the higher dose cut body weight by 13.2 percent compared with 3.9 percent on placebo.

Average HbA1c, a HbA1c, a three month average of blood sugar levels, dropped by 1.5 percentage points on the higher dose.

Improvements in waist size also appeared in the diabetes group. The reduction averaged 6.5 centimeters, about 2.6 inches, which signals less central fat.

Safety and side effects

Across both studies, gastrointestinal symptoms were the most common side effects. Nausea and diarrhea tended to appear early during dose increases and often eased with time.

In the adult trial without diabetes, gastrointestinal events were reported in 71 percent on 7.2 mg, 61 percent on 2.4 mg, and 43 percent on placebo.

Reports of dysaesthesia, abnormal tingling or burning feelings, were more frequent at the higher dose, and the investigators noted this imbalance clearly.

Serious adverse events remained in a similar range across groups. In the diabetes trial, the risk of hypoglycaemia, episodes of low blood sugar, was low and comparable between semaglutide doses and placebo.

Doctors and patients weigh these trade offs with shared decision making. The risk pattern here resembled what is already known for this class of medicines.

How this fits current care

In the United States, the approved maintenance dose for chronic weight management is 2.4 mg once weekly, per the product label. Clinicians increase the dose slowly to improve tolerability.

The trials evaluated a higher weekly maintenance dose for people who do not meet goals on the approved dose. This approach aims to help more people reach clinically meaningful loss without surgery.

Trial duration and follow up matter. The STEP UP trial ran 72 weeks with a 9 week follow up, according to the public record.

Waist size reductions deserve attention because they relate to fat around abdominal organs. Larger waists link with higher risk of diabetes and heart problems.

Next steps for semaglutide dose

Long term maintenance beyond a year and a half still needs careful study. Weight loss plateaus, side effect persistence, and strategies for dose adjustments over several years remain open questions.

The results land amid a broader public health challenge. More than two in five U.S. adults have obesity and many also live with conditions like type 2 diabetes and high blood pressure.

New options matter for people who have tried standard dosing without enough benefit. Real world access, adherence, and counseling on diet and physical activity will shape outcomes.

Future studies will need to test durability of benefits and whether higher doses change long term risks. Researchers will also look at quality of life, physical function, and how best to support safe use.

The study is published in The Lancet Diabetes & Endocrinology.

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