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Risk Factors for Hypoglycemia in Type 2 Diabetes Mellitus Patients Using Once-Weekly Semaglutide: A Matched Case-Control Study.

Source: PubMed, NCBI / U.S. National Library of Medicine

Therapeutics and clinical risk managementAmirthalingam Palanisamy, Alarawi Fawaz Ahmed, Jassas Alagwar Loay Mohammed, et al.Published 1/1/2026Last synced 6/11/2026Status: syncedPMID: 42266882DOI: 10.2147/TCRM.S610579

The semaglutide once-weekly injection (Sema-OWI) is widely accepted for managing type-2 diabetes mellitus (T2DM) patients, particularly those seeking weight loss. However, hypoglycemia is continually challenging healthcare practitioners, and the underlying factors have yet to be conclusively reported. The study aimed to investigate the underlying characteristics of T2DM patients undergoing sema-OWI treatment. A matched case-control study design was employed with a 1:4 (case:control) ratio. Univariable conditional logistic regression was used for the preliminary analysis of the association between patient characteristics and the occurrence of hypoglycemia using a matched odds ratio (mOR). Then, multivariable conditional logistic regression was performed using the predictors, with adjusted mOR (mORadj), including body mass index (BMI) and glycosylated hemoglobin (HbA1C), adjusted for the significant confounders identified in the univariable conditional logistic regression. Forty-five cases diagnosed with the hypoglycemic event and 180 controls were recruited according to a 1:4 (case:control) ratio. According to univariable conditional logistic regression, Patients treated with sema-OWI for 4-6 months (mOR = 0.052; p<0.001) and more than 6 months (mOR = 0.045; p = 0.001) were least likely to experience hypoglycemia. Obese patients (mOR = 0.110; p = 0.041) and those with an HbA1C level >9 (mOR = 0.254; p < 0.001) were also least likely to experience hypoglycemia. According to mul

Abstract

The semaglutide once-weekly injection (Sema-OWI) is widely accepted for managing type-2 diabetes mellitus (T2DM) patients, particularly those seeking weight loss. However, hypoglycemia is continually challenging healthcare practitioners, and the underlying factors have yet to be conclusively reported. The study aimed to investigate the underlying characteristics of T2DM patients undergoing sema-OWI treatment. A matched case-control study design was employed with a 1:4 (case:control) ratio. Univariable conditional logistic regression was used for the preliminary analysis of the association between patient characteristics and the occurrence of hypoglycemia using a matched odds ratio (mOR). Then, multivariable conditional logistic regression was performed using the predictors, with adjusted mOR (mORadj), including body mass index (BMI) and glycosylated hemoglobin (HbA1C), adjusted for the significant confounders identified in the univariable conditional logistic regression. Forty-five cases diagnosed with the hypoglycemic event and 180 controls were recruited according to a 1:4 (case:control) ratio. According to univariable conditional logistic regression, Patients treated with sema-OWI for 4-6 months (mOR = 0.052; p<0.001) and more than 6 months (mOR = 0.045; p = 0.001) were least likely to experience hypoglycemia. Obese patients (mOR = 0.110; p = 0.041) and those with an HbA1C level >9 (mOR = 0.254; p < 0.001) were also least likely to experience hypoglycemia. According to multivariable conditional logistic regression analysis, the model was adjusted for the number of T2DM medications and Sema-OWI duration, confirming that obesity and higher HbA1C levels (>9) were associated with a lower likelihood of hypoglycemia. On the other hand, the above results establish that the normal body mass index and lower HbA1C levels (<7) were associated with a higher likelihood of hypoglycemia. Patients with T2DM treated with sema-OWI require careful monitoring, particularly during the first 3 months. Normal BMI and HbA1C levels <7 are considered risk factors for hypoglycemia.

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