S4488 GLP-1 Agonists and Dyspeptic Symptoms: A Case Series in the Ambulatory Setting

Introduction: Glucagon-like peptide-1 (GLP-1) receptor agonists are a new class of anti-hyperglycemic agents which are being utilized in large numbers to treat type 2 diabetes mellitus (T2DM) among other conditions. As mimetics of the endogenous secretagogue, these drugs potentiate insulin, stabilize post-prandial glucose, and importantly, delay gastric emptying. Patients with DM can develop delayed gastric emptying, dyspepsia, and frank gastroparesis through direct action of glucose on enteric motility and hyperglycemia-induced loss of neurons. There is little literature existing that examines symptom changes in this patient population at risk for delayed gastric emptying following treatment with this class of drugs. Here we report on a case series of 2 patients assessed with validated symptom rating scales over time. Case Description: Patients with T2DM were identified in the ambulatory setting who met criteria for treatment with GLP-1 agonists. They were administered a battery of 3 surveys prior to treatment: the Gastroparesis Cardinal Symptom Index (GCSI), Patient Assessment of Upper GI Quality of Life (PAGI-QOL), and Gastrointestinal Symptom Rating Scale (GSRS). Patient 1 is a 47-year-old woman with hypertension, history of HIV well-controlled with antiretrovirals, long-standing T2DM managed with insulin and oral agents who sought to start a GLP-1 agonist for increased glycemic control and weight loss. Patient 2 is a 33-year-old man with hypertension and bipolar 1 disorder whose T2DM was managed with oral anti-hyperglycemic medications and was looking to start GLP-1 agonists for the added weight benefits. Both patients had poorly controlled diabetes at the initiation of the GLP-1 agonists, with hemoglobin A1C above 8%. They were initially screened for gastroparesis with the GCSI, which was negative. Initial composite GSRS scores were 14.7 and 28.2, respectively. Initial PAGI-QOL were high, indicating poor quality of life due to symptoms (113 and 50). Notably, there was improvement in both patients in overall PAGI-QOL, decreasing to 23 for Patient 1 and 17 for Patient 2. Composite GSRS was also decreased for both patients, 8.3 for Patient 1 and 1 for Patient 2. Discussion: The unexpected response to these drugs highlights the variable effects they can have on dyspeptic symptoms in patients with T2DM. We continue to follow these patients to get a better sense of factors that may predict gastrointestinal effects of GLP-1 agonists in vivo.