Low-Dose Semaglutide Can Ease Insulin Need in Early T1D, Small Series Shows

When used very early on in type 1 diabetes, a GLP-1 receptor agonist may help reduce the need for insulin, a small case series suggested.

Ten adults with a new type 1 diabetes diagnosis initially received a 0.125-mg dose of weekly semaglutide (Ozempic), which was adjusted up to a maximum of 0.5 mg per week as prandial insulin was adjusted down.

Within 3 months of starting semaglutide, all of the patients were completely off prandial insulin. Within 6 months, seven patients were also able to eliminate basal insulin, reported Paresh Dandona, MD, PhD, of the State University of New York at Buffalo in Williamsville, New York, and colleagues, who detailed their findings in a New England Journal of Medicine correspondence.

“In all, our preliminary observations support the need for prospective, randomized clinical trials with larger numbers of patients to investigate this approach further,” the researchers suggested.

Though widely used for type 2 diabetes and obesity, no GLP-1 receptor agonists or SGLT2 inhibitors are currently approved by the FDA for type 1 diabetes. While some agents have been submitted to the agency for review, none have actually nabbed a type 1 diabetes indication, often due to concerns about diabetic ketoacidosis and hypoglycemia from the agents’ dramatic glucose lowering capabilities.

The current case series followed patients ages 21 to 39 at the State University of New York at Buffalo from 2020 to 2022. Half were female, all but one were white, and their average baseline body mass index was 25.1. Four initially presented with diabetic ketoacidosis at the time of diagnosis while the others presented with polyuria, polydipsia, and weight loss. A total of nine patients had antibodies against glutamic acid decarboxylase, and one had autoantibodies against islet antigen 2.

Patients were started on semaglutide within 3 months of their diagnosis, as “most patients with new-onset type 1 diabetes have substantial intact beta-cell reserve,” the researchers noted. While medication doses were being adjusted, carbohydrate intake was restricted for all patients.

Mean HbA1c dropped from 11.7±2.1% at baseline down to 5.9±0.3% by the 6-month mark of semaglutide treatment. This continued to drop a bit more, falling to 5.7±0.4% at 12 months.

Patients on semaglutide also saw a significant rise in mean fasting C-peptide levels, from 0.65±0.33 ng/mL at baseline up to 1.05±0.40 ng/mL by the end of the study and patients spent 89±3% of time in range as measured by continuous glucose monitoring.

As they had no control arm, the researchers compared their HbA1c data with the control groups of four studies involving patients with early type 1 diabetes, where initial improvement in HbA1c was only observed during the first 6 months.

“Thereafter, they all showed an increase in the glycated hemoglobin level, a finding that was consistent with the end of the so-called ‘honeymoon period’ in the treatment of early type 1 diabetes,” Dandona and coauthors wrote.

As is the concern in type 1 diabetes, the researchers pointed out that only mild hypoglycemia was seen during the semaglutide dose titration. After the dose was stabilized, none of the patients experienced any episodes of hypoglycemia. Likewise, there were no events of diabetic ketoacidosis or other serious adverse events.

At baseline, the average total insulin dose was 0.35±0.11 U/kg, while basal and bolus insulin doses were 0.21±0.12 U/kg and 0.15±0.09 U/kg, respectively.

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