Efficacy of Once Weekly Semaglutide in Patients With Type 2 Diabetes: a Non Randomized Clinical Trial

This single-arm, non-randomized, off-label clinical trial evaluated the efficacy and safety of once-weekly semaglutide in adults with type 2 diabetes mellitus and obesity who had inadequate glycemic control despite receiving standard glucose-lowering therapy. The study was conducted at two diabetes care centers in Peshawar, Pakistan, between July 2022 and March 2023. The protocol was approved by the Institutional Review Board of Rehman Medical Institute, Peshawar, and written informed consent was obtained from all participants before enrollment.

Adults aged 18 years or older were eligible if they had established type 2 diabetes mellitus for at least six months, glycated hemoglobin levels between 7.5% and 10.0%, and a body mass index of at least 30 kg/m² despite ongoing diabetes treatment. Participants were excluded if they had type 1 diabetes mellitus, gestational diabetes, severe renal impairment, previous or current treatment with a glucagon-like peptide-1 receptor agonist, chronic pancreatitis, pancreatic malignancy, diabetic retinopathy requiring active treatment, significant ocular complications, pregnancy, lactation, or known thyroid disease or thyroid neoplasms.

Eligible participants received subcutaneous semaglutide once weekly for a total treatment period of 16 weeks. Semaglutide was initiated at a dose of 0.25 mg once weekly for the first four weeks and was then increased to 0.5 mg once weekly for the following 12 weeks. Participants who were taking dipeptidyl peptidase-4 inhibitors discontinued those medications before starting semaglutide. Other background glucose-lowering medications, including metformin, sodium-glucose cotransporter-2 inhibitors, sulfonylureas, and basal insulin, were continued at the discretion of the treating physician unless clinical adjustment was required.

All participants received standardized counseling regarding dietary modification, physical activity, medication adherence, injection technique, and the recognition and management of possible adverse effects. Treatment adherence was assessed during follow-up through participant interviews and inspection of used injection pens.

Baseline demographic and clinical data included age, sex, duration of diabetes, body weight, height, body mass index, fasting blood glucose, random blood glucose, glycated hemoglobin, systolic and diastolic blood pressure, and lipid profile. Participants attended a follow-up visit at four weeks to assess adherence, dose escalation, tolerability, and adverse events. At the end of the 16-week treatment period, the baseline clinical and biochemical measurements were repeated.