Increased Risk of Hypoglycemia Following Roux-en-Y Gastric Bypass Surgery in Patients Without Diabetes: a Propensity Score-Matched Analysis

Abstract

Background: Roux-en-Y gastric bypass (RYGB) surgery is an effective treatment for obesity. However, the incidence and long-term risk of hypoglycemia after surgery in patients without diabetes remains unclear. This study aimed to investigate the prevalence of hypoglycemia following RYGB surgery in patients with obesity and without diabetes.

Methods: A retrospective cohort study was conducted using the TriNetX database. The study population included 15,085 patients with obesity (BMI ≥ 30 kg/m²) who underwent RYGB surgery and 3,200,074 non-surgical controls, all without a history of diabetes or GLP-1 receptor agonist use. Propensity score matching was performed to balance baseline characteristics. The primary outcome was the incidence of hypoglycemia, defined by ICD-10-CM codes or laboratory values (glucose ≤ 70 mg/dL). Cox regression analysis was employed to calculate hazard ratios (HR) and 95% confidence intervals (CI).

Results: In the overall study population, the risk of hypoglycemia was significantly higher in the RYGB group (18.70%, n = 2,810) compared to the control group (3.80%, n = 120,923; HR 4.3, 95% CI 4.14-4.46, p < 0.001). After propensity score matching (n = 14,916 per group), RYGB patients maintained an elevated risk (18.70%, n = 2,795) compared to matched controls (5.0%, n = 749; HR 3.7, 95% CI 3.44-4.05, p < 0.001). Time-series analysis revealed consistently higher hypoglycemia risk in the RYGB group, with hazard ratios ranging from 5.37 (95% CI 4.09-7.03) at 1 week to 3.75 (95% CI 3.45-4.06) at 10 years post-surgery (all p < 0.001). Subgroup analysis of RYGB patients who developed hypoglycemia showed a 30-day hospitalization rate of 21.3% and a mortality rate of 0.71%.

Conclusion: RYGB surgery is associated with a significantly increased risk of hypoglycemia in patients with obesity and without diabetes, both in the short-term and long-term follow-up. These findings underscore the importance of monitoring and managing hypoglycemia in patients undergoing RYGB surgery, even in the absence of preexisting diabetes.

Keywords: Bariatric surgery; Hypoglycemia; Obesity; Propensity score matching; Roux-en-Y gastric bypass.

Fig. 1

Prevalence of hypoglycemia in the overall study population before and after propensity score matching. The risk of hypoglycemia was significantly higher in the RYGB surgery group compared to the non-surgical control group, both before and after propensity score matching (p < 0.001)

Fig. 2

Time-series follow-up of propensity score-matched cohorts. A Incidence of hypoglycemia at various time points following RYGB surgery compared to non-surgical controls. The incidence of hypoglycemia remained significantly elevated in the RYGB surgery group throughout the 10-year follow-up period (all p < 0.001)

Fig. 3

Risk of hypoglycemia at each time point following RYGB or obesity diagnosis. Cox regression analysis was employed, and hazards ratio (HR) and 95% confidence intervals (CI) are reported. The risk of hypoglycemia remained significantly elevated in the RYGB surgery group throughout the 10-year follow-up period (all p < 0.001)