The pill form of the drug semaglutide is worth pursuing as a way to control blood sugar in patients with type 2 diabetes, say researchers.

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Semaglutide in the form of a pill may help type 2 diabetes patients to achieve better glycemic control.

So concluded a phase II clinical trial that found that the pill was better at glycemic control than a placebo over a 26-week period.

A report on the trial — by lead author Dr. Melanie Davies, of the Diabetes Research Centre at the University of Leicester in the United Kingdom, and colleagues — has been published in JAMA.

The results justify phase III trials to assess the longer-term effects and safety of semaglutide in pill form to help patients with type 2 diabetes to control blood sugar, note the authors.

More than 90 percent of the 30 million people living with diabetes in the United States have type 2 diabetes, which is a condition that develops when the body cannot use insulin properly to help cells turn blood sugar, or glucose, into energy.

Many patients can manage their type 2 diabetes by eating a healthful diet, partaking in exercise, and taking medications to help control blood sugar, or achieve glycemic control.

To select the right medication, doctors need to consider the complexity of the treatment and the risk of side effects, such as low blood sugar, or hypoglycemia, and weight gain.

One option is the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide, which is currently administered as an injection.

However, the authors suggest that a pill version of semaglutide might be more acceptable for some patients and thus increase the number of people who follow the recommended regimen to reduce their risk of complications.

Before a new version of a drug can be approved, it must undergo a series of clinical trials. In a phase II trial, different doses of the drug are compared with a “dummy,” or placebo. Then, if the results are favorable, the drug progresses to a larger, phase III trial to test its effectiveness and safety.

For their phase II trial of the pill version of semaglutide, Dr. Davies and her colleagues enrolled 632 type 2 diabetes patients whose current treatment was not achieving sufficient glycemic control, for instance through diet and exercise, or through use of metformin.

The researchers randomly assigned the patients to several groups, all of which underwent treatment for 26 weeks. Some groups received a daily pill version of semaglutide or a placebo, while others received a weekly injection of semaglutide. Those who received the pill version were in groups that received different fixed daily doses, or gradually escalating daily doses.

The main measure used by the team to evaluate the effectiveness of the drug was the effect on patients’ hemoglobin Alc (HbA1c) levels. The HbA1c test checks the amount of glucose that is attached to hemoglobin, which is the oxygen-carrying protein in red blood cells.

The results showed that the average change in HbA1c over the 26 weeks of the trial fell in all the groups, with the biggest fall being in the group that received semaglutide by injection.

However, all dosages of the pill form of semaglutide reduced average HbA1c “significantly more than placebo by week 26,” note the authors.

The reduction in average HbA1c in the oral semaglutide groups ranged from -0.7 percent to -1.9 percent, depending on dosage, while reductions in the placebo group were -0.3 percent. In the group that received semaglutide by injection, the average reduction was -1.9 percent.

Of the patients who received the pill form of semaglutide, between 44 and 90 percent (depending on dosage) achieved the target level of HbA1c of under 7 percent, having started at an average of 7.9 percent at baseline.

The results also show that 71 percent of patients on the pill form of semaglutide achieved a “clinically relevant” weight loss of 5 percent or more. Overweight and obesity are significant contributors to type 2 diabetes.

The side effects of taking the oral version were similar to those that occur with the injectable form of semaglutide.

The authors conclude that, in the type 2 diabetes patients on whom they tested it, the pill form of semaglutide achieved better glycemic control than placebo over 26 weeks. They say:

These findings support phase III studies to assess longer-term and clinical outcomes, as well as safety.”

They note that the study has several limitations, with the main one being that it only lasted for 26 weeks. The team suggests that future studies should also test the effect of oral semaglutide in participants with higher levels of HbA1c “to explore its potential in patients who are less well controlled, and in combination with other glucose-lowering agents.”